Seeing Beyond the Surface: Superior performance of Ultrasound elastography over Milan ultrasound criteria in distinguishing fibrosis of ulcerative colitis.

BACKGROUND: Colonic fibrosis has important clinical implications in ulcerative colitis. Ultrasound imaging has emerged as a convenient and reliable tool in diagnosis of inflammatory bowel disease. We aimed to explore the potential use of ultrasound to evaluate UC fibrosis. METHODS: Consecutive UC patients who had proctocolectomy from July 2022 to Sep 2023 were enrolled in the study. Patients underwent bowel ultrasound examination and ultrasound elastography imaging prior to surgery. Milan ultrasound criteria (MUC) was calculated and bowel wall stiffness was determined using two mean strain ratios (MSRs). Degree of colonic fibrosis and inflammation was measured upon histological analysis. ROC analysis was used to evaluate the performance of ultrasound-derived parameters to predict fibrosis. RESULTS: Fifty-six patients were enrolled with 112 segments included in analysis. The median fibrosis score was 2 (0-4) and the median Geboes score was 5 (0-13) and these two scores were significantly correlated (p<0.001). The muscularis mucosa thickness was significantly higher in moderate-severe fibrosis than none-mild fibrosis (p=0.003) but bowel wall thickness was not (p=0.082). The strain ratios (p<0.001) and MUC (p=0.010) was significantly higher in involved than non-involved segments. The strain ratios were correlated with fibrosis score (p<0.001) but not MUC (p=0.387). At ROC analysis, MSR1 had an AUC of 0.828 (cutoff value 3.07, 95% CI 0.746-0.893, p<0.001) to predict moderate-severe fibrosis. CONCLUSION: Ultrasound elastography imaging could predict the degree of colonic fibrosis in UC. Application of this technique could help disease monitoring and decision-making of UC patients.

Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Promote Survival of Random Flaps in Rats through NRF2-Mediated Antioxidative Stress.

BACKGROUND: Random flaps are the most used defect repair method for head and neck tumors and trauma plastic surgery. The distal part of the flap often undergoes oxidative stress (OS), ultimately leading to flap necrosis. Stem cells exosomes exhibit potential effects related to anti-inflammatory, regenerative, and antioxidant properties. Nuclear factor erythroid-2-related factor 2 (Nrf2) is an important factor in regulating oxidative balance. Exosomes have been reported to monitor its transcription to alleviate OS. This study examined the impacts and underlying mechanisms of antioxidant actions of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exo) on random flaps. METHODS: BMSCs-Exo was injected into the tail veins of rats on days 0, 1, and 2 after surgery of random flaps. The rats were euthanized on day 3 to calculate the survival rate. Immunohistochemical staining, western blotting, dihydroethidium probe, superoxide dismutase, and malondialdehyde assay kits were used to detect OS level. Human umbilical vein endothelial cells were co-cultured with BMSCs-Exo and ML385 (an inhibitor of Nrf2) in vitro. RESULTS: BMSCs-Exo may significantly improve the survival rate of the random flaps by reducing apoptosis, inflammation, and OS while increasing angiogenesis. Besides, BMSCs-Exo can also increase mitochondrial membrane potential and reduce reactive oxygen species levels in vitro. These therapeutic effects might stem from the activation of the Keap1/Nrf2 signaling pathway. CONCLUSION: BMSCs-Exo improved the tissue antioxidant capacity by regulating the keap1/Nrf2 signaling pathway. BMSCs-Exo may be a new strategy to solve the problem of random flap necrosis.

Construction of efficient and environmentally friendly bio-based flame retardant cotton fabric through layer by layer self-assembly of alkylammonium functional silsesquioxane/phosphorylated sodium alginate.

As an important source of green cleaning flame retardants, bio-based materials have been widely studied by researchers. However, the development of efficient biobased flame retardants and convenient finishing methods was of great significance for the functional finishing of materials. Herein, a convenient and efficient flame retardant cotton fabric was prepared via layer by layer self-assembly (LbL) by alternating precipitation of a novel bio-based flame retardant phosphorylated sodium alginate (PSA) and alkylammonium functionalized siloxane (A-POSS). The effect of coating number on flame retardancy and thermal properties of coated cotton fabric was systematically studied. Thermogravimetric analysis (TGA) results showed that residual char contents of AP/PS-15BL under air and N2 atmospheres increased by 252.0% and 225.2%, respectively, compared with control cotton. In vertical flammability tests, both the AP/PS-10BL and AP/PS-15BL showed self-extinguishing behavior and successfully passed the UL-94 V-0 rating. More importantly, the LOI value of AP/PS-15BL was significantly increased to 35.0% from 20.0% of pure cotton fabric. Additionally, coated samples showed good mechanical properties and washable resistance. In CONE test, the peak heat release rate (PHRR) and total heat release rate (THR) of AP/PS-15BL decreased by 89.3% and 49.3% respectively, compared with control cotton. Therefore, this green and convenient flame-retardant finishing method has great application potential in the multi-functional finishing of cotton fabrics.

Development and validation of an ultrasound-based deep learning radiomics nomogram for predicting the malignant risk of ovarian tumours.

BACKGROUND: The timely identification and management of ovarian cancer are critical determinants of patient prognosis. In this study, we developed and validated a deep learning radiomics nomogram (DLR_Nomogram) based on ultrasound (US) imaging to accurately predict the malignant risk of ovarian tumours and compared the diagnostic performance of the DLR_Nomogram to that of the ovarian-adnexal reporting and data system (O-RADS). METHODS: This study encompasses two research tasks. Patients were randomly divided into training and testing sets in an 8:2 ratio for both tasks. In task 1, we assessed the malignancy risk of 849 patients with ovarian tumours. In task 2, we evaluated the malignancy risk of 391 patients with O-RADS 4 and O-RADS 5 ovarian neoplasms. Three models were developed and validated to predict the risk of malignancy in ovarian tumours. The predicted outcomes of the models for each sample were merged to form a new feature set that was utilised as an input for the logistic regression (LR) model for constructing a combined model, visualised as the DLR_Nomogram. Then, the diagnostic performance of these models was evaluated by the receiver operating characteristic curve (ROC). RESULTS: The DLR_Nomogram demonstrated superior predictive performance in predicting the malignant risk of ovarian tumours, as evidenced by area under the ROC curve (AUC) values of 0.985 and 0.928 for the training and testing sets of task 1, respectively. The AUC value of its testing set was lower than that of the O-RADS; however, the difference was not statistically significant. The DLR_Nomogram exhibited the highest AUC values of 0.955 and 0.869 in the training and testing sets of task 2, respectively. The DLR_Nomogram showed satisfactory fitting performance for both tasks in Hosmer-Lemeshow testing. Decision curve analysis demonstrated that the DLR_Nomogram yielded greater net clinical benefits for predicting malignant ovarian tumours within a specific range of threshold values. CONCLUSIONS: The US-based DLR_Nomogram has shown the capability to accurately predict the malignant risk of ovarian tumours, exhibiting a predictive efficacy comparable to that of O-RADS.

Ultrasound-based deep learning radiomics model for differentiating benign, borderline, and malignant ovarian tumours: a multi-class classification exploratory study.

BACKGROUND: Accurate preoperative identification of ovarian tumour subtypes is imperative for patients as it enables physicians to custom-tailor precise and individualized management strategies. So, we have developed an ultrasound (US)-based multiclass prediction algorithm for differentiating between benign, borderline, and malignant ovarian tumours. METHODS: We randomised data from 849 patients with ovarian tumours into training and testing sets in a ratio of 8:2. The regions of interest on the US images were segmented and handcrafted radiomics features were extracted and screened. We applied the one-versus-rest method in multiclass classification. We inputted the best features into machine learning (ML) models and constructed a radiomic signature (Rad_Sig). US images of the maximum trimmed ovarian tumour sections were inputted into a pre-trained convolutional neural network (CNN) model. After internal enhancement and complex algorithms, each sample's predicted probability, known as the deep transfer learning signature (DTL_Sig), was generated. Clinical baseline data were analysed. Statistically significant clinical parameters and US semantic features in the training set were used to construct clinical signatures (Clinic_Sig). The prediction results of Rad_Sig, DTL_Sig, and Clinic_Sig for each sample were fused as new feature sets, to build the combined model, namely, the deep learning radiomic signature (DLR_Sig). We used the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) to estimate the performance of the multiclass classification model. RESULTS: The training set included 440 benign, 44 borderline, and 196 malignant ovarian tumours. The testing set included 109 benign, 11 borderline, and 49 malignant ovarian tumours. DLR_Sig three-class prediction model had the best overall and class-specific classification performance, with micro- and macro-average AUC of 0.90 and 0.84, respectively, on the testing set. Categories of identification AUC were 0.84, 0.85, and 0.83 for benign, borderline, and malignant ovarian tumours, respectively. In the confusion matrix, the classifier models of Clinic_Sig and Rad_Sig could not recognise borderline ovarian tumours. However, the proportions of borderline and malignant ovarian tumours identified by DLR_Sig were the highest at 54.55% and 63.27%, respectively. CONCLUSIONS: The three-class prediction model of US-based DLR_Sig can discriminate between benign, borderline, and malignant ovarian tumours. Therefore, it may guide clinicians in determining the differential management of patients with ovarian tumours.

Contrast-enhanced ultrasound for the preoperative prediction of pathological characteristics in breast cancer.

Objective: We aimed to investigate the value of contrast-enhanced ultrasound (CEUS) in the preoperative prediction of the histological grades and molecular subtypes of breast cancer. Methods: A total of 183 patients with pathologically confirmed breast cancer were included. Contrast enhancement patterns and quantitative parameters were compared in different groups. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of CEUS in the preoperative prediction of pathological characteristics, including histologic grade and molecular subtypes. Results: Heterogeneous enhancement, perfusion defects, and peripheral radial vessels were mostly observed in higher histologic grade (grade III) breast cancer. Heterogeneous enhancement and perfusion defect were the most effective indicators for grade III breast cancer, with the areas under the ROC curve of 0.768 and 0.756, respectively. There were significant differences in the enhancement intensity, post-enhanced margin, perfusion defects, and peripheral radial vessel among the different molecular subtypes of breast cancer (all P < 0.01). Perfusion defects and clear edge after enhancement were the best qualitative criteria for the diagnosis of HER-2 overexpressed and triple-negative breast cancers, and the corresponding areas under the ROC curves were 0.804 and 0.905, respectively. There were significant differences in PE, WiR, WiPI, and WiWoAUC between grade III vs grade I and II breast cancer (P < 0.05). PE, WiR, WiPI, and WiWoAUC had good efficiency in the diagnosis of high-histologic-grade breast cancer. PE had the highest diagnostic efficiency in Luminal A, while WiPI had the highest diagnostic efficiency in Luminal B subtype breast cancer, and the areas under the ROC curve were 0.825 and 0.838, respectively. WiWoAUC and WiR were the most accurate parameters for assessing triple-negative subtype breast cancers, and the areas under the curve were 0.932 and 0.922, respectively. Conclusion: Qualitative and quantitative perfusion analysis of contrast-enhanced ultrasound may be useful in the non-invasive prediction of the histological grade and molecular subtypes of breast cancers.

Outcomes of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: validation, comparison and improvement of 2022 ELN genetic risk system.

The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and 224 (37.33%) patients in ELN-2022 favorable-, intermediate-, and adverse-risk group respectively and 86 patients (14.33%) experienced a shift in risk stratification compared to ELN-2017. Median and maximum follow-up time were 2.89 (95% CI 2.67 to 3.03) years and 8.78 years. The median overall survival (OS) was 73.8% (95% CI 67.5% to 80.3%), 63.9% (95% CI 56.7% to 72.0%) and 57.6% (95% CI 50.4% to 65.9%) in ELN-2022 favorable-, intermediate-, and adverse-risk group (P < 0.001). OS shortened significantly as the ELN-2022 risk stratification increased but didn't significantly in ELN-2017 intermediate-risk compared to favorable-risk. Both ELN-2022 and ELN-2017 adverse-risk were associated with increased cumulative incidence of relapse (CIR). Time-dependent receiver operating characteristic (ROC) analysis showed that both ELN-2017 and ELN-2022 risk systems had limited prognostic ability for OS. We modified ELN-2022 risk system with pre-transplant minimal residual disease (MRD) and the modified risk system performed a significantly superior efficacy to ELN-2022 system.

Computed tomography-based nomogram of Siewert type II/III adenocarcinoma of esophagogastric junction to predict response to docetaxel, oxaliplatin and S-1.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become the standard care for advanced adenocarcinoma of esophagogastric junction (AEG), although a part of the patients cannot benefit from NAC. There are no models based on baseline computed tomography (CT) to predict response of Siewert type II or III AEG to NAC with docetaxel, oxaliplatin and S-1 (DOS). AIM: To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS. METHODS: One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS, and were randomly and consecutively assigned to the training cohort (TC) (n = 94) and the validation cohort (VC) (n = 34). Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors (version 1.1) criteria. Possible prognostic factors associated with responses after DOS treatment including Siewert classification, gross tumor volume (GTV), and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age. Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS. A nomogram was established based on independent factors to predict the response. The predictive performance of the nomogram was evaluated by Concordance index (C-index), calibration and receiver operating characteristics curve in the TC and VC. RESULTS: Univariate analysis showed that Siewert type (52/55 vs 29/39, P = 0.005), pretherapeutic cT stage (57/62 vs 24/32, P = 0.028), GTV (47.3 ± 27.4 vs 73.2 ± 54.3, P = 0.040) were significantly associated with response to DOS in the TC. Multivariate analysis of the TC also showed that the pretherapeutic cT stage, GTV and Siewert type were independent predictive factors related to response to DOS (odds ratio = 4.631, 1.027 and 7.639, respectively; all P < 0.05). The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC (C-index: 0.838 and 0.824), with area under the receiver operating characteristic curve of 0.838 and 0.824, respectively. The calibration curves showed that the practical and predicted response to DOS effectively coincided. CONCLUSION: A novel nomogram developed with pretherapeutic cT stage, GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.

Addition of PD-1/PD-L1 inhibitors to chemotherapy for triple-negative breast cancer: a meta-analysis.

Background: In recent years, the addition of immune checkpoint inhibitors (ICI) to chemotherapy (CT) has become a research hotspot in the therapy of metastatic triple-negative breast cancer. Nevertheless, controversial results have been revealed among the published randomized controlled trials. Hence, a meta-analysis was performed to assess the therapeutic effect of this treatment regimen. Methods: Five English databases (PubMed, WOS, CENTRAL, Scopus, and Embase), and four Chinese databases (CBM, CNKI, VIP, and Wanfang), as well as oncological meetings, were systematically searched to identify eligible studies that assessed the addition of ICI to CT versus CT alone in metastatic triple-negative breast cancer. The pooled hazard ratios (HR) of progression-free survival (PFS) and overall survival (OS) were estimated using fixed- or random-effect model. Subgroup analyses were also performed in the intention-to-treat (ITT) and PD-L1-positive individuals. Results: All told there are five eligible randomized controlled trials involving 3,000 patients were enrolled in this meta-analysis. Compared with CT alone, the ICI plus CT regimen significantly increased PFS in the ITT (HR = 0.80, 95% CI: 0.73-0.88) and PD-L1-positive (HR = 0.70, 95% CI: 0.62-0.79) populations, as well as OS in the ITT (HR = 0.89, 95% CI: 0.81-0.97) and PD-L1-positive populations (HR = 0.80, 95% CI: 0.71-0.91). Moreover, the PFS of sufferers treated with the combination strategy of ICI with CT increased alongside PD-L1 enrichment. A clinical benefit in terms of objective response rate was also distinctly observed in both populations treated with ICI plus CT. In the subgroup analysis, patients in the no prior CT subgroup experienced a striking increase in PFS in both populations; however, a difference was not observed in other subgroups. Conclusions: The combination strategy striking improves PFS and OS in both ITT and PD-L1-positive populations, and PFS is prolonged with PD-L1 enrichment. Patients who do not receive CT prior to this treatment are associated with longer PFS in both populations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42021289817.

Contrast-enhanced CT radiomics features to preoperatively identify differences between tumor and proximal tumor-adjacent and tumor-distant tissues of resectable esophageal squamous cell carcinoma.

BACKGROUND: Esophagectomy is the main treatment for esophageal squamous cell carcinoma (ESCC), and patients with histopathologically negative margins still have a relatively higher recurrence rate. Contrast-enhanced CT (CECT) radiomics might noninvasively obtain potential information about the internal heterogeneity of ESCC and its adjacent tissues. This study aimed to develop CECT radiomics models to preoperatively identify the differences between tumor and proximal tumor-adjacent and tumor-distant tissues in ESCC to potentially reduce tumor recurrence. METHODS: A total of 529 consecutive patients with ESCC from Centers A (n = 447) and B (n = 82) undergoing preoperative CECT were retrospectively enrolled in this study. Radiomics features of the tumor, proximal tumor-adjacent (PTA) and proximal tumor-distant (PTD) tissues were individually extracted by delineating the corresponding region of interest (ROI) on CECT and applying the 3D-Slicer radiomics module. Patients with pairwise tissues (ESCC vs. PTA, ESCC vs. PTD, and PTA vs. PTD) from Center A were randomly assigned to the training cohort (TC, n = 313) and internal validation cohort (IVC, n = 134). Univariate analysis and the least absolute shrinkage and selection operator were used to select the core radiomics features, and logistic regression was performed to develop radiomics models to differentiate individual pairwise tissues in TC, validated in IVC and the external validation cohort (EVC) from Center B. Diagnostic performance was assessed using area under the receiver operating characteristics curve (AUC) and accuracy. RESULTS: With the chosen 20, 19 and 5 core radiomics features in TC, 3 individual radiomics models were developed, which exhibited excellent ability to differentiate the tumor from PTA tissue (AUC: 0.965; accuracy: 0.965), the tumor from PTD tissue (AUC: 0.991; accuracy: 0.958), and PTA from PTD tissue (AUC: 0.870; accuracy: 0.848), respectively. In IVC and EVC, the models also showed good performance in differentiating the tumor from PTA tissue (AUCs: 0.956 and 0.962; accuracy: 0.956 and 0.937), the tumor from PTD tissue (AUCs: 0.990 and 0.974; accuracy: 0.952 and 0.970), and PTA from PTD tissue (AUCs: 0.806 and 0.786; accuracy: 0.760 and 0.786), respectively. CONCLUSION: CECT radiomics models could differentiate the tumor from PTA tissue, the tumor from PTD tissue, and PTA from PTD tissue in ESCC.

LINC02561 promotes metastasis in HCC via HIF1-α/NDRG1/UPF1 axis.

In the entire world, hepatocellular carcinoma (HCC) is one of the most frequent cancers that lead to death. Experiments on the function of long non-coding RNAs in the emergence of malignancies, including HCC, are ongoing. As a crucial RNA monitoring mechanism in eucaryotic cells, nonsense-mediated mRNA decay (NMD) can recognize and destroy mRNAs, which has an premature termination codons (PTC) in the open reading frame to prevent harmful buildup of truncated protein products in the cells. Nonsense transcript regulator 1 (Up-frameshift suppressor 1, UPF1), as a highly conserved RNA helicase and ATPase, plays a key role in NMD. Our laboratory screened out the highly expressed lncRNA LINC02561 in HCC from the TCGA database. Further research found that LINC02561 enhanced the invasion and transition abilities of liver cancer cells by regulating the protein N-Myc downstream regulated 1 (NDRG1). Hypoxia inducible factor-1 (HIF-1α) can bonded to LINC02561 promoters under hypoxic conditions, thereby promoting the upregulation of LINC02561 expression in liver cancer cells. LINC02561 competes with NDRG1 mRNA to bind UPF1, thereby preventing the degradation of NDRG1 mRNA to facilitate NDRG1 protein level. Taken together, the HIF1α-LINC02561-UPF1-NDRG1 regulatory axis could be an entirely novel target of liver cancer-related treatment.

Refractory patients with favorable/intermediate-risk acute myeloid leukemia benefit from azacytidine maintenance therapy following allogeneic hematopoietic stem cell transplantation.

Recurrence following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major cause of treatment failure in patients with myeloid malignancy. Azacytidine (AZA) maintenance is a promising therapy to prevent relapse and improve survival. We conducted a prospective, one-arm study involving 78 patients with myeloid malignancy at a high risk of recurrence who were enrolled between September 2019 and April 2022. Furthermore, 102 matched historical controls were selected using propensity score matching. With a median follow-up time of 19.6 (3.5-91.7) months, AZA maintenance therapy significantly improved relapse-free survival (RFS; log-rank test, p = 0.01). The AZA and control groups had a 1-year RFS of 87.7% (95% confidence interval [CI], 0.80-0.96) and 72.2% (95% CI, 0.64-0.82), respectively, with a hazard ratio (HR) of 0.21 (95% CI, 0.09-0. 47; p < 0.01). There were no grade 4 adverse effects or deaths related to AZA. Refractory patients with favorable/intermediate-risk acute myeloid leukemia (AML) benefited more from AZA maintenance therapy than those with adverse-risk AML according to the European Leukemia Net guidelines (RFS in favorable/intermediate-risk AML, HR = 0.29, 95% CI, 0.11-0.79; RFS in adverse-risk AML, HR = 0.57, 95% CI, 0.21-1.6; p for interaction = 0.03). Our findings suggest that AZA maintenance therapy following allo-HSCT was safe and could reduce the incidence of relapse, particularly for refractory patients with favorable/intermediate-risk AML.

A novel AluYb8 insertion-associated non-coding RNA, lncMUTYH, impairs mitochondrial function and dampens the M2-like polarization of macrophages.

An inverted AluYb8 insertion in the MUTYH intron 15 (AluYb8MUTYH variant) has been reported to be associated with reduced MUTYH1 expression and mitochondrial dysfunction with age. However, the underlying mechanism remains unknown. In this study, we identified a novel transcript associated with the AluYb8MUTYH variant, which revealed that this transcript is about 780 nucleotides in length with a poly-A tail, lacks protein-coding potential, referred to as lncMUTYH. The results from the reporter gene system confirmed that the lncMUTYH down-regulates MUTYH1 expression at the translational level. Site-directed mutagenesis on the 5'-terminal exon sequences of α-MUTYH and lncMUTYH constructs revealed that lncMUTYH can act as a trans-regulator that depends on the partial base pairing between its exonized AluYb8 sequence and the 5'UTR of α-MUTYH to impede MUTYH 1 expression. Furthermore, we have demonstrated a correlation between decreased mitochondrion-localized MUTYH1 caused by lncMUTYH and lowered levels of mitochondrial biological function indicators, such as mtDNA content, mitochondrial regulatory gene expression, oxygen consumption rate, ATP product, and mitochondrial respiratory capacity. Notably, we found that lncMUTYH inhibited the M2-like polarization of macrophages, and CD68/CD206-positive cell fractions were significantly lower in lncMUTYH ectopically expressing cells. The results confirmed that the AluYb8MUTYH-associated lncMUTYH, derived from an AluYb8 insertion mutation, acts as a trans-regulatory factor that inhibits the MUTYH1 protein expression, leading to a progressive mitochondrial dysfunction that may disrupt macrophage differentiation. In summary, lncMUTYH can contribute to AluYb8MUTYH-associated mitochondrial dysfunction with age and hamper the macrophage polarization process, potentially increasing the risk of developing age-related diseases.

A novel non-coding RNA was identified derived from the AluYb8 insertion in the MUTYH gene, namely lncMUTYH.LncMUTYH selectively decreased the MUTYH1 protein localized in mitochondrial, which is dependent on the sequence and orientation derived from AluYb8 insertion.Overexpression of lncMUTYH dampens the mitochondrial function and M2-like polarization of macrophages, partly due to the suppression of the MUTYH1 protein.

Recombinant human adenovirus p53 combined with transcatheter arterial chemoembolization for liver cancer: A meta-analysis.

OBJECTIVES: To compare the clinical curative effects, survival and complications of recombinant human adenovirus-p53 (rAd-p53) combined with transcatheter arterial chemoembolization (TACE) versus TACE for the treatment of liver cancer. METHODS: We searched all the eligible studies of rAd-p53 plus TACE versus control group had only TACE in the treatment of liver cancer, which were retrieved from CNKI, Wanfang database, CBM, VIP, PubMed, EMBase, The Chrance of Library, Web of Science from its inception to august 2022. RESULTS: A total of 17 studies were included, which involved 1045 patients. The results of the meta analysis indicated that the the rAd-p53combined with TACE markedly improved the patients' complete remission(OR = 2.19, 95% CI:1.13-4.22, P = 0.02), partial remission (OR = 2.22, 95% CI:1.67-2.94, P<0.00001), objective tumor response rate (OR = 2.58, 95% CI:1.95-3.41, P<0.00001) and disease control rate(OR = 2.39, 95% CI:1.65-3.47, P<0.00001) compared with TACE alone. And our results showed that rAd-p53combined with TACE had better survival benefit [6-month OS (OR = 3.41, 95% CI: 1.62-7.14, p = 0.001); 1-year OS (OR = 1.95, 95% CI: 1.28-2.96, p = 0.002)] and better quality of life(MD = 5.84, 95% CI:2.09-9.60, P = 0.002). In addition, the immunity of the patients was enhanced by the combination therapy, as demonstrated by the increase in the ratio of CD4+ to CD4+/CD8+. In adverse effects, except for fever in the TACE combined with rAd-p53 group, which was higher than that in the TACE group(OR = 2.62, 95% CI:2.02-3.49, P<0.00001), all other adverse effects were lower in the TACE combined with rAd-p53 group than in the TACE group. CONCLUSION: RAd-p53 combined with TACE for liver cancer showed significant advantages in terms of clinical efficacy, survival rate, and safety compared to the TACE alone, and effectively improved patient quality of life and immune function. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2022-9-0127/.

Exosomes derived from bone marrow mesenchymal stem cells regulate pyroptosis via the miR-143-3p/myeloid differentiation factor 88 axis to ameliorate intestinal ischemia-reperfusion injury.

Intestinal ischemia-reperfusion (I/R) injury is a condition in which tissue injury is aggravated after ischemia due to recovery of blood supply. Bone marrow mesenchymal stem cell-derived exosome (BMSC-exo) showed a protective effect on I/R injury. This study aimed to investigate the possible mechanisms by which BMSC-exos ameliorate intestinal I/R injury. We isolated mouse BMSC-exos by super-centrifugation and found that they effectively increased cell viability in a cell model, alleviated intestinal barrier injury in a mouse model, and downregulated the expression of inflammatory cytokines and pyroptosis-related proteins, suggesting that BMSC-exos may alleviate intestinal I/R injury in vitro and in vivo by regulating pyroptosis. We identified miR-143-3p as a differentially expressed miRNA by microarray sequencing. Bioinformatic analysis predicted a binding site between miR-143-3p and myeloid differentiation factor 88 (MyD88); a dual-luciferase reporter assay confirmed that miR-143-3p could directly regulate the expression of MyD88. Our findings suggest that miR-143-3p regulates pyroptosis by regulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) through the toll-like receptor (TLR)-4/MyD88/nuclear factor kappa-B (NF-кB) pathway. This study describes a potential strategy for the treatment of intestinal I/R injury using BMSC-exos that act by regulating pyroptosis through the miR-143-3p mediated TLR4/MyD88/NF-кB pathway.

BMSC-exos ameliorate intestinal ischemia/reperfusion (I/R) injurymiR-143-3p levels were reduced in I/R injury and increased with BMSC-exo treatmentmiR-143-3p directly targeted and downregulated the expression of MyD88BMSC-exos regulate pyroptosis in intestinal I/R injury via the miR-143-3p-MyD88 axis.

A CT-based novel model to predict pathological complete response of locally advanced esophageal squamous cell carcinoma to neoadjuvant PD-1 blockade in combination with chemotherapy.

PURPOSE: To develop a novel CT-based model to predict pathological complete response (pCR) of locally advanced esophageal squamous cell carcinoma (ESCC) to neoadjuvant PD-1 blockade in combination with chemotherapy. METHODS: 117 consecutive patients with locally advanced ESCC were stratified into training cohort (n = 82) and validation cohort (n = 35). All patients underwent non-contrast and contrast-enhanced thoracic and upper abdominal CT before neoadjuvant PD-1 blockade in combination with chemotherapy (CTpre), and after two cycles of the therapy before esophagectomy (CTpost), respectively. Univariate analyses and binary logistic regression analyses of ESCC quantitative and qualitative CT features were performed to determine independent predictors of pCR. Prediction performance of the model developed with independent predictors from training cohort was evaluated by receiver operating characteristic (ROC) analysis, and validated by Kappa test in validation cohort. RESULTS: In training cohort, the difference in CT attenuation between tumor and background normal esophageal wall obtained from CTpre (ΔTNpre), tumoral increased CT attenuation after contrast-enhanced scan from CTpost images (ΔTpost) and gross tumor volume (GTV) from CTpre were independent predictors of pCR (odds ratio = 1.128 (95% confidence interval (CI): 0.997-1.277), 1.113 (95%CI: 0.965-1.239) and 1.133 (95%CI: 1.043-1.231), respectively, all P-values < 0.05). Logistic regression model equation (0.121 × ΔTNpre + 0.107 × ΔTpost + 0.125 × GTV - 9.856) to predict pCR showed the best performance with an area under the ROC of 0.876, compared with each independent predictor. The good performance was confirmed by the Kappa test (K-value = 0.796) in validation cohort. CONCLUSIONS: This novel model can be reliable to predict pCR to neoadjuvant PD-1 blockade in combination with chemotherapy in locally advanced ESCC.

Application of prophylactic or pre-emptive therapy after allogeneic transplantation for high-risk patients with t(8;21) acute myeloid leukemia.

OBJECTIVES: To determine the impact of pretransplant measurable residual disease (pre-MRD) and the efficacy of maintenance therapy in t(8;21) acute myeloid leukemia (AML) patients after allogeneic hematopoietic cell transplantation (allo-HCT). METHODS: We retrospectively analyzed 100 t(8;21) AML patients who underwent allo-HCT between 2013 and 2022. 40 patients received pre-emptive therapy including immunosuppressant adjustment, azacitidine, and donor lymphocyte infusion (DLI) combined with chemotherapy. 23 patients received prophylactic therapy, including azacitidine or chidamide. RESULTS: Patients with a positive pre-MRD (pre-MRDpos) had a higher 3-year cumulative incidence of relapse (CIR) (25.90% [95% CI, 13.87%-39.70%] vs 5.00% [95% CI, 0.88%-15.01%]; P = 0.008). Pre-MRDpos patients were less likely to have a superior 3-year disease-free survival (DFS) (40.83% [95% CI, 20.80%-80.16%]) if their MRD was still positive at 28 days after transplantation (post-MRD28pos). The 3-year DFS and CIR were 53.17% (95% CI, 38.31% - 73.80%) and 34.87% (95% CI, 18.84% - 51.44%), respectively, for patients receiving pre-emptive interventions after molecular relapse. The 3-year DFS and CIR were 90.00% (95%CI, 77.77% - 100%) and 5.00% (95%CI, 0.31% - 21.10%), respectively, for high-risk patients receiving prophylactic therapy. In most patients, epigenetic-drug-induced adverse events were reversible with dose adjustment or temporary discontinuation. CONCLUSION: Patients with pre-MRDpos and post-MRD28pos were more likely to have higher rates of relapse and inferior DFS, even after receiving pre-emptive interventions. Prophylactic therapy may be a better option for high-risk t(8;21) AML patients; however, this warrants further investigation.

Herombopag promotes platelet engraftment and decreases platelet transfusion after allogeneic hematopoietic stem cell transplantation.

The delayed platelet engraftment associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common complication and often results in increased transplant-related complications. A single-center, prospective, investigator-initiated pilot study was conducted to explore whether herombopag, a second generation thrombopoietin-receptor agonist, would promote platelet engraftment after allo-HSCT. Between 2/2022 and 06/2022, 17 individuals (median age 39; range 15-58 years) with hematological malignancies were enrolled. Herombopag was given for a median of 22 (range 14-61) days at a dose of 7.5 mg/d. The median time to neutrophil >500/µl was 11 (range 9-19) days. The median time to platelet >20 000/µl and >50 000/µl was 13 (range 8-22), and 20 (range 14-45) days, respectively. Compared with historical controls, the cumulative incidence of platelet engraftment after HSCT was significantly higher in the herombopag group (>20 000/µl at day +21, 88% vs 65%, p = .003; >50 000/µl at day +30, 65% vs. 43%, p = .001). Herombopag also reduced the units of platelet transfusion within 30 days post-SCT (3.6 ± 2.5 vs. 5.4 ± 3.2 U, p = .01). In conclusion, it seems likely that herombopag could enhance platelet engraftment after allo-HSCT.

Non-CpG sites preference in G:C > A:T transition of TP53 in gastric cancer of Eastern Europe (Poland, Romania and Hungary) compared to East Asian countries (China and Japan).

AIM: Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions. SUBJECTS AND METHOD: In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C > A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data. RESULTS: The most frequent base substitutions were G:C > A:T transition in all the areas investigated. The G:C > A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C > A:T transition in CpG sites and A:T > G:C mutation was more prevalent in Asian countries. CONCLUSION: The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.