Long non-coding RNA NEAT1 serves as a novel biomarker for treatment response and survival profiles via microRNA-125a in multiple myeloma.

BACKGROUND: The present study aimed to explore the association of long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) with multiple myeloma (MM) risk and further investigate its correlation with clinical features, treatment response, survival profiles, and its interaction with microRNA-125a (miR-125a) in MM patients. METHODS: Totally, 114 de novo symptomatic MM patients and 30 healthy donors (as controls) were recruited. Their bone marrow samples were collected before treatment (MM patients) and at enrollment (healthy donors), respectively. Subsequently, plasma cells were isolated from bone marrow for detection of lncRNA NEAT1 and miR-125a expression via reverse transcription quantitative polymerase chain reaction. RESULTS: lncRNA NEAT1 was upregulated in MM patients compared with healthy donors and presented with excellent value in distinguishing MM patients from healthy donors. In MM patients, lncRNA NEAT1 positively associated with International Staging System (ISS) stage, beta-2 microglobulin (ß2-MG), and lactate dehydrogenase (LDH), but not correlated with core cytogenetics and other clinical features. Furthermore, lncRNA NEAT1 negatively associated with complete remission (CR), overall remission rate (ORR), progression-free survival (PFS), and overall survival (OS). Moreover, lncRNA NEAT1 negatively associated with miR-125a in MM patients. MiR-125a was downregulated in MM patients compared with healthy donors, and it negatively associated with ISS stage, ß2-MG, and LDH, but positively correlated with CR, ORR, PFS, and OS in MM patients. CONCLUSION: lncRNA NEAT1 might interact with miR-125a, and serves as a novel biomarker for treatment response and survival profiles in MM, indicating its clinical value for MM management.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy.

BACKGROUND Increasing evidence suggests that cancer-associated inflammation is associated with poorer outcomes. The neutrophil-to-lymphocyte ratio (NLR), considered as a systemic inflammation marker, is thought to predict prognoses in colorectal cancer. In this study, we explored the association between the NLR and prognoses following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). MATERIAL AND METHODS From February 2002 to December 2012, a group of 202 patients diagnosed with LARC and receiving neoadjuvant CRT followed by radical surgery was included in our retrospective study. The associations between the pre-CRT NLR and clinicopathological characteristics, as well as the predictive value of pre-CRT NLR against survival outcomes, were analyzed. RESULTS The average NLR was 2.7±1.5 (median 2.4, range 0.6-12.8). There were 63 (31.2%) patients with NLR ≥3.0, and 139 (68.8%) patients with NLR <3.0. Correlation analyses showed that no clinicopathological characteristics except age were associated with NLR. We did not find an association between NLR and survival outcomes. In multivariate Cox model analyses, the R1/R2 resection, lymph node ratio ≥0.1, and perineural/lymphovascular invasion were independently associated with worse disease-free survival and overall survival. CONCLUSIONS In our cohort, the NLR did not correlate with survival outcomes in LARC patients undergoing neoadjuvant CRT. The prognostic value of NLR should be validated in large-scale prospective studies.

Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer.

PURPOSE: The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS: Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate. RESULTS: Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %. CONCLUSION: These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.

Prognostic value of phospho-Akt in patients with non-small cell lung carcinoma: a meta-analysis.

Previous studies have been inconsistent with respect to the reported associations between phospho-Akt (p-Akt) overexpression and lung cancer prognosis. In this study, we conducted a systematic review and meta-analysis to assess the prognostic value of p-Akt in patients with non-small cell lung carcinoma (NSCLC). Relevant articles were identified by searching MEDLINE. Hazard risks (HRs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed. Finally, 18 studies comprising 2,353 patients were included in the meta-analysis. p-Akt overexpression was associated with worse survival in NSCLC patients, and the pooled HRs for all the studies was 1.38 (95% confidence interval [CI]: 1.11-1.70; p<0.01). After subgroup analysis, the association was strengthened in the surgery treatment group, with an HR of 1.44 (95% CI: 1.19-1.75; p<0.01), while in the tyrosine kinase inhibitors treatment group, the statistical significance disappeared (HR: 1.22, 95% CI: 0.70-2.14; p=0.48). The HR in cases of early stage disease (I-III) was 1.35 (95% CI: 1.08-1.69; p=0.04); however, in cases of late stage disease (III-IV), the association became non-significant (HR: 1.22, 95% CI: 0.64-2.33; p=0.54). Our results suggest that there was a significantly inverse association between p-Akt overexpression and the prognosis of NSCLC patients, and that this association appeared to be limited in early-stage patients who underwent surgery.

Ultra-Wideband Transformer Feedback Monolithic Microwave Integrated Circuit Power Amplifier Design on 0.25 µm GaN Process.

This paper presents an ultra-wideband transformer feedback (TFB) monolithic microwave integrated circuit (MMIC) power amplifier (PA) developed using a 0.25 µm gallium nitride (GaN) process. To broaden the bandwidth, a drain-to-gate TFB technique is employed in this PA design, achieving a 117% relative -3 dB bandwidth, extending from 5.4 GHz to 20.3 GHz. At a 28 V supply, the designed PA circuit achieves an output power of 25.5 dBm and a 14 dB small-signal gain in the frequency range of 6 to 19 GHz. Within the 6 to 19 GHz frequency range, the small-signal gain exhibits a flatness of less than 0.78 dB. The PA chip occupies an area of 1.571 mm2. This work is the first to design a power amplifier with on-chip transformer feedback in a compound semiconductor MMIC process, and it enables the use of the widest bandwidth power amplifier on-chip transformer matching network.

Deep learning models for ischemic stroke lesion segmentation in medical images: A survey.

This paper provides a comprehensive review of deep learning models for ischemic stroke lesion segmentation in medical images. Ischemic stroke is a severe neurological disease and a leading cause of death and disability worldwide. Accurate segmentation of stroke lesions in medical images such as MRI and CT scans is crucial for diagnosis, treatment planning and prognosis. This paper first introduces common imaging modalities used for stroke diagnosis, discussing their capabilities in imaging lesions at different disease stages from the acute to chronic stage. It then reviews three major public benchmark datasets for evaluating stroke segmentation algorithms: ATLAS, ISLES and AISD, highlighting their key characteristics. The paper proceeds to provide an overview of foundational deep learning architectures for medical image segmentation, including CNN-based and transformer-based models. It summarizes recent innovations in adapting these architectures to the task of stroke lesion segmentation across the three datasets, analyzing their motivations, modifications and results. A survey of loss functions and data augmentations employed for this task is also included. The paper discusses various aspects related to stroke segmentation tasks, including prior knowledge, small lesions, and multimodal fusion, and then concludes by outlining promising future research directions. Overall, this comprehensive review covers critical technical developments in the field to support continued progress in automated stroke lesion segmentation.

Classification of recurrent major depressive disorder using a residual denoising autoencoder framework: Insights from large-scale multisite fMRI data.

BACKGROUND AND OBJECTIVE: Recurrent major depressive disorder (rMDD) has a high recurrence rate, and symptoms often worsen with each episode. Classifying rMDD using functional magnetic resonance imaging (fMRI) can enhance understanding of brain activity and aid diagnosis and treatment of this disorder. METHODS: We developed a Residual Denoising Autoencoder (Res-DAE) framework for the classification of rMDD. The functional connectivity (FC) was extracted from fMRI data as features. The framework addresses site heterogeneity by employing the Combat method to harmonize feature distribution differences. A feature selection method based on Fisher scores was used to reduce redundant information in the features. A data augmentation strategy using a Synthetic Minority Over-sampling Technique algorithm based on Extended Frobenius Norm measure was incorporated to increase the sample size. Furthermore, a residual module was integrated into the autoencoder network to preserve important features and improve the classification accuracy. RESULTS: We tested our framework on a large-scale, multisite fMRI dataset, which includes 189 rMDD patients and 427 healthy controls. The Res-DAE achieved an average accuracy of 75.1 % (sensitivity = 69 %, specificity = 77.8 %) in cross-validation, thereby outperforming comparison methods. In a larger dataset that also includes first-episode depression (comprising 832 MDD patients and 779 healthy controls), the accuracy reached 70 %. CONCLUSIONS: We proposed a deep learning framework that can effectively classify rMDD and 33 identify the altered FC associated with rMDD. Our study may reveal changes in brain function 34 associated with rMDD and provide assistance for the diagnosis and treatment of rMDD.

Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells.

BACKGROUND: Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action. METHOD: An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action. RESULTS: Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD. CONCLUSION: This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis.

Effects of hydromorphone-based patient-controlled intravenous analgesia on postoperative hypoxaemia: a randomised controlled non-inferiority clinical trial.

OBJECTIVE: This study aimed to compare the effects of patient-controlled intravenous analgesia (PCIA) with and without low-basal infusion on postoperative hypoxaemia. DESIGN: A randomised parallel-group non-inferiority trial. SETTING: The trial was conducted at a grade-A tertiary hospital from December 2021 to August 2022. PARTICIPANTS: 160 adults undergoing gastrointestinal tumour surgery and receiving postoperative PCIA. INTERVENTIONS: Participants randomly received a low-basal (0.1 mg/hour of hydromorphone) or no-basal infusion PCIA for postoperative 48 hours. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was area under curve (AUC) per hour for hypoxaemia, defined as pulse oxygen saturation (SpO2) <95%. Secondary outcomes included: AUC per hour at SpO2<90% and <85%, hydromorphone consumption, ambulation time and analgesic outcomes up to 48 hours after surgery. RESULTS: Among 160 randomised patients, 159 completed the trial. An intention-to-treat analysis showed that AUC per hour (SpO2<95%) was greater in the low-basal infusion group compared with the no-basal infusion group, with a median difference of 0.097 (95% CI 0.001 to 0.245). Non-inferiority (margin: ratio of means (ROM) of 1.25) was not confirmed since the ROM between the two groups was 2.146 (95% CI 2.138 to 2.155). Hydromorphone consumption was higher in the low-basal group than in the no-basal group (median: 5.2 mg versus 1.6 mg, p<0.001). Meanwhile, there were no differences in the AUC values at the other two hypoxaemia thresholds, in ambulation time, or pain scores between the groups. CONCLUSIONS: Among the patients receiving hydromorphone PCIA after gastrointestinal tumour resection, low-basal infusion was inferior to no-basal infusion PCIA for postoperative hypoxaemia at SpO2<95% up to 48 hours after surgery. TRIAL REGISTRATION NUMBER: ChiCTR2100054317.

Development and validation of a prognostic nomogram for gastrointestinal stromal tumors in the postimatinib era: A study based on the SEER database and a Chinese cohort.

BACKGROUND: After the standardization, recording and follow-up of imatinib use that significantly prolongs survival of gastrointestinal stromal tumors (GISTs), a comprehensive reassessment of the prognosis of GISTs is necessary and more conductive to treatment options. METHODS: A total of 2185 GISTs between 2013 and 2016 were obtained from the Surveillance, Epidemiology, and End Results database and comprised our training (n = 1456) and internal validation cohorts (n = 729). The risk factors extracted from univariate and multivariate analyses were used to establish a predictive nomogram. The model was evaluated and tested in the validation cohort internally and in 159 patients with GIST diagnosed between January 2015 and June 2017 in Xijing Hospital externally. RESULTS: The median OS was 49 months (range, 0-83 months) in the training cohort and 51 months (0-83 months) in the validation cohort. The concordance index (C-index) of the nomogram was 0.777 (95% CI, 0.752-0.802) and 0.7787 (0.7785, bootstrap corrected) in training and internal validation cohorts, respectively, and 0.7613 (0.7579, bootstrap corrected) in the external validation cohort. Receiver operating characteristic curves and calibration curves for 1-, 3-, and 5-year overall survival (OS) showed a high degree of discrimination and calibration. The area under the curve showed that the new model performed better than the TNM staging system. In addition, the model could be dynamically visualized on a webpage. CONCLUSION: We developed a comprehensive survival prediction model for assessing the 1-, 3- and 5-year OS of patients with GIST in the postimatinib era. This predictive model outperforms the traditional TNM staging system and sheds light on the improvement of the prognostic prediction and the selection of treatment strategies for GISTs.

A small-scale, exploratory real-world study of nab-paclitaxel combined with oxaliplatin and tegafur in the perioperative treatment of advanced gastric cancer: a study protocol for a real-world clinical trial.

Background: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an optimized and improved derivative of paclitaxel with superior efficacy and fewer adverse reactions, and it is widely used in the treatment of advanced gastric cancer. However, there is a paucity of data regarding the safety and efficacy of nab-paclitaxel combined with oxaliplatin (LBP) and tegafur in the treatment of patients with advanced gastric cancer. Methods: This analysis is a prospective, single-center, open-label, historically controlled real-world study designed to include 10 patients with advanced gastric cancer treated with nab-paclitaxel combined with LBP and tegafur gimeracil oteracil potassium. The primary and main efficacy outcomes are safety indicators, including the incidence of adverse drug reactions and adverse events (AEs), as well as the outliers of laboratory indicators and vital signs. The secondary efficacy outcomes are overall survival (OS), objective response rate (ORR), disease control rate (DCR), and proportion of dose suspensions, dose reductions and discontinuations. Discussion: Based on the findings of previous studies, we wished to assess the safety and efficacy of nab-paclitaxel combined with LBP and tegafur in the treatment of advanced gastric cancer. The trial requires constant contact and monitoring. The purpose is to determine a superior protocol in terms of patient survival, and pathological and objective response. Trial Registration: This trial has been registered with the Clinical Trial Registry: NCT05052931 (registration date: 2021/9/12).

Melatonin inhibits ferroptosis and delays age-related cataract by regulating SIRT6/p-Nrf2/GPX4 and SIRT6/NCOA4/FTH1 pathways.

BACKGROUND: Cataracts are the main cause of reversible blindness worldwide. The ageing of the lens caused by ultraviolet B (UVB) radiation is mostly related to oxidative stress (OS). Little is known about whether OS induced by UVB enhances the sensitivity of lens epithelial cells to ferroptotic stress, which may be a new mechanism leading to age-related cataracts (ARCs). METHODS: Ferroptosis was detected by transmission electron microscopy (TEM), iron assay, lipid peroxidation (MDA) assay, real-time PCR, western blotting, and immunofluorescence. Genetic engineering technology was used to investigate the regulatory relationship among Sirtuin 6 (SIRT6), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear receptor coactivator 4 (NCOA4), glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH1). Knockdown and overexpression of SIRT6 locally in vivo in rats were performed to probe the regulatory mechanism of SIRT6 in ferroptosis in ARCs. FINDINGS: Here, we observed that UVB can drastically induce ferroptosis in lens epithelial cells in vivo and in vitro. Surprisingly, inhibition of ferroptosis was the direct reason that melatonin rescued B-3, SRA01/04 and HEK-293 T cells survival; the pan-caspase inhibitor Z-Vad-FMK did not significantly reverse the death of UVB-irradiated cells compared with that in the UVB+DMSO group. SIRT6 was an upstream regulator of phosphorylated Nrf2 (p-Nrf2) and NCOA4 in B-3, SRA01/04 and HEK-293 T cells. Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats. INTERPRETATION: Our findings reveal a novel causal role of melatonin in the pathogenesis of ARCs, which raises the possibility of selectively targeting the activation of SIRT6 and ferroptotic resistance as a latent antioxidative therapeutic strategy for ARCs.

M1 macrophage predicted efficacy of neoadjuvant camrelizumab combined with chemotherapy vs chemotherapy alone for locally advanced ESCC: A pilot study.

Introduction: The efficacy and safety of immunotherapy have been widely recognized in gastrointestinal-related cancers. However, the efficacy of neoadjuvant camrelizumab for locally advanced esophageal squamous cell carcinoma (ESCC) has not been firmly established. This study compared the efficacy of camrelizumab in combination with neoadjuvant DCF (docetaxel, cisplatin and fluorouracil), with DCF alone for ESCC, and exploring biomarkers related to immune infiltration of the ESCC immunotherapy response. Methods: We enrolled and randomly assigned patients with stage II-IVa ESCC to two study treatments: camrelizumab combined with docetaxel, cisplatin and fluorouracil (DCF) regimen and DCF regimen alone. The tissue for multiplex immunofluorescence (mIF) was obtained before and after neoadjuvant therapy. The Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1) and Tumor Regression Grade (TRG) was used to evaluate efficacy. Results: A total of 30 patients were enrolled in the study. Following neoadjuvant camrelizumab, the objective response rate (ORR) and the disease control rate (DCR) were 46.7% (7/15) and 95.7% (14/15), respectively. No patients reported complete remission, while ORR and DCR in the chemotherapy group were 26.7% (4/15) and 86.7% (13/15), respectively. R0 resection after neoadjuvant treatment was achieved in 3 out of 15 patients in the combined group and in all patients (15/15) in the chemotherapy group. In the combined group, M1-type tumor-associated macrophages and CD56dim NK cells were more abundant in responders than in non-responders (p < 0.05). A higher M1/M2 ratio was observed in responders (p < 0.05). With respect to the NGS, among the copy number amplified genes, the 11q13 amplicon (CCND1/FGF19/FGF4/FGF3) showed the highest frequency (47%, 7/15). Conclusions: Neoadjuvant camrelizumab combined with chemotherapy improved ORR in locally advanced ESCC. M1-type tumor-associated macrophages and CD56dim NK cells might be utilized to predict camrelizumab efficacy.

Programmed death-ligand 1 and mammalian target of rapamycin signaling pathway in locally advanced rectal cancer.

PURPOSE: To evaluate the role of programmed death-ligand 1 (PD-L1) and mammalian target of rapamycin (mTOR) signaling pathway in locally advanced rectal cancer (LARC). METHODS: Between February 2012 and February 2018, 103 patients with LARC treated by neoadjuvant chemoradiotherapy (neoCRT) and total mesorectal excision (TME) were included. PD-L1, mTOR and p-mTOR of pair-matched pre-neoCRT biopsies and post-neoCRT surgical tissue were evaluated by immunohistochemistry. RESULTS: The mean combined positive score (CPS), tumor proportion score (TPS) and immune cell score (IC) of pre-neoCRT were 2.24 (0-70), 1.87 (0-70) and 0.67 (0-10), respectively. The mean CPS, TPS and IC of post-neoCRT were 2.19 (0-80), 1.38 (0-80) and 1.60 (0-20), respectively. Significant difference was observed in terms of IC between pre-neoCRT and post-neoCRT (p = 0.010). The 5-year disease-free survival (DFS) rate of the whole group was 62.4%. Multivariate analysis by Cox model indicated that pre-neoCRT TPS [hazard ratio (HR) 1.052, 95% confidence interval (CI) 1.020-1.086, p = 0.001] and post-neoCRT CPS (HR 0.733, 95% CI 0.555-0.967, p = 0.028) were associated with DFS. In the 89 patients without pathological complete response, p-mTOR and IC were upregulated after neoCRT. CONCLUSIONS: For patients with LARC treated by neoCRT and TME, p-mTOR and IC were upregulated after neoCRT. Pre-neoCRT TPS and post-neoCRT CPS were independent prognostic predictors of DFS.

Glasgow prognostic score and combined positive score for locally advanced rectal cancer.

Purpose: This study was performed to investigate the association of Glasgow prognostic score (GPS), combined positive score (CPS), and clinicopathological characteristics of locally advanced rectal cancer. Methods: Between February 2012 and February 2018, 103 patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy and total mesorectal excision (TME) were retrospectively evaluated. Results: According to the classification of the GPS, 85 (82.5%), 13 (12.6%), and 5 patients (4.9%) were classified as a score of 0, 1, and 2, respectively. Patients were classified into the GPS-low group (GPS of 0, n = 85) and GPS-high group (GPS of 1 or 2, n = 18) with an area under the curve of 0.582 for overall survival (OS). The mean programmed death-ligand 1 (PD-L1) CPS of the whole group was 2.24 (range, 0-70). The PD-L1 CPS of the GPS-high group was higher than the GPS-low group (P < 0.001). Multivariate analysis by Cox proportional hazards model indicated that GPS was associated with OS and disease-free survival (DFS). Furthermore, PD-L1 CPS was associated with DFS (hazard ratio, 1.050; 95% confidence interval, 1.017-1.083; P = 0.003). Conclusion: Elevated GPS was related to the PD-L1 CPS. GPS and PD-L1 CPS were associated with the prognosis of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by TME.

Effects of hydromorphone-based intravenous patient-controlled analgesia with and without a low basal infusion on postoperative hypoxaemia: study protocol for a randomised controlled clinical trial.

INTRODUCTION: When patients receive patient-controlled intravenous analgesia (PCIA), no basal infusion is always recommended, as the addition of a basal infusion increases the occurrence of postoperative opioid-induced respiratory depression. However, few studies have investigated whether low basal infusions increase the incidence of postoperative hypoxaemia relative to no basal infusion. We intend to conduct a clinical trial to test the hypothesis that PCIA with a low basal infusion does not increase the occurrence of postoperative hypoxaemia relative to PCIA with no basal infusion. METHODS AND ANALYSIS: This single-centre parallel randomised controlled clinical trial will be conducted with 160 patients undergoing gastrointestinal tumour surgery. The assigned nurse will set analgesic pumps (low or no basal infusion PCIA) according to block-based randomisation sequence. Other investigators and all participants will be blinded to intervention allocation. All patients will be monitored continuously with the ep pod, a wireless wearable device, recording of oxygen saturation (SpO2) and daily ambulation duration for 48 hours postoperatively. Three follow-up evaluations will be conducted to assess the analgesic effect (Numeric Rating Scale (NRS) pain score) and opioid-related side effects (Overall Benefit of Analgesic Score (OBAS)). The primary outcome will be the area under the curve for hypoxaemia (defined as SpO2<95%) per hour. The secondary outcomes will be the areas under the curve for hypoxaemia defined as SpO2<90% and <85% per hour, hydromorphone consumption, OBASs at 24 and 48 hours postoperatively, NRS scores at 4, 24 and 48 hours postoperatively, and the ambulation time per hour over 48 hours. ETHICS AND DISSEMINATION: The study has been approved by the Xijing Hospital Ethics Committee (KY20212163-F-1). Written informed consent will be obtained from all patients or their authorised surrogates. All data will be managed with confidentiality. Findings will be disseminated at international conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2100054317.

miR­576­5p promotes epithelial­to­mesenchymal transition in colorectal cancer by targeting the Wnt5a­mediated Wnt/ß­catenin signaling pathway.

Colorectal cancer (CRC) is one of the most common types of malignancy and the third most commonly diagnosed form of cancer worldwide, ranking as the fourth leading cause of cancer­associated mortality. MicroRNA (miR)­576­5p has been reported to be highly expressed in patients with CRC; however, its biological role remains unclear. The present study aimed therefore to investigate the biological role and underlying mechanism of miR­576­5p in CRC cell line SW480. The viability of SW480 cells following transfection with miR­576­5p mimic or inhibitor was analyzed using MTT assay. Wound healing and Transwell assays were performed to determine the cell migratory and invasive abilities, respectively. A dual luciferase reporter assay was used to verify the predicted binding site between miR­576­5p and Wnt5a. Reverse transcription­quantitative PCR and western blotting were used to analyze the expression levels of miR­576­5p, E­cadherin, N­cadherin, vimentin, Snail1, Wnt5a, ß­catenin, c­myc, cyclin D1 and p/t­c­Jun. Using bioinformatics analysis, high expression of miR­576­5p was found not only in tumor tissues, compared with the normal tissue, but also in CRC cells, compared with NCM460 cells. Furthermore, the inhibition of miR­576­5p expression significantly decreased the cell viability and the migratory and invasive abilities of SW480 cells, and suppressed the epithelial­to­mesenchymal transition (EMT). In addition, miR­576­5p could interact with Wnt5a and regulate the expression level of Wnt5a in order to influence the activity of Wnt/ß­catenin signaling. The results from rescue experiments further demonstrated that the effect of miR­576­5p overexpression on cell metastasis and EMT was reversed by Wnt5a overexpression or treatment with XAV­939, which is an inhibitor of the Wnt/ß­catenin signaling pathway. In conclusion, the findings from the present study suggested that inhibition of miR­576­5p may suppress SW480 cell metastasis and EMT by targeting Wnt5a and regulating the Wnt5a­mediated Wnt/ß­catenin signaling pathway, providing a potential therapeutic target for the treatment of CRC.

Janus kinase 2/signal transducers and activators of transcription signal inhibition regulates protective effects of probucol on mesangial cells treated with high glucose.

Probucol is a cholesterol-lowering drug with an anti-proliferative effect. Excessive growth of glomerular mesangial cells and overexpression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) are the pathological features of diabetic nephropathy. In this study, human mesangial cells (HMCs) treated with high glucose showed the above-mentioned features through the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT) pathway. Probucol can suppress cell proliferation, down-regulate mRNA and protein levels of TGF-beta1 and CTGF in HMCs treated with high glucose. Phosphorylation of JAK2, STAT1 and STAT3 caused by high glucose was obviously prevented in HMCs pretreated with probucol, indicating that the protective effect of probucol on HMCs might be through the inhibition of JAK2/STAT pathway. Therefore, probucol could be a potential therapeutic agent for diabetic nephropathy, and this paper provides new insights into the molecular mechanisms underlying probucol's effects.

Straw decreased N2O emissions from flooded paddy soils via altering denitrifying bacterial community compositions and soil organic carbon fractions.

Straw return is widely applied to increase soil fertility and soil organic carbon storage. However, its effect on N2O emissions from paddy soil and the associated microbial mechanisms are still unclear. In this study, wheat straw was amended to two paddy soils (2% w/w) from Taizhou (TZ) and Yixing (YX), China, which were flooded and incubated for 30 d. Real-time PCR and Illumina sequencing were used to characterize changes in denitrifying functional gene abundance and denitrifying bacterial communities. Compared to unamended controls, straw addition significantly decreased accumulated N2O emissions in both TZ (5071 to 96 mg kg-1) and YX (1501 to 112 mg kg-1). This was mainly due to reduced N2O production with decreased abundance of major genera of nirK and nirS-bacterial communities and reduced nirK and nirS gene abundances. Further analyses showed that nirK-, nirS- and nosZ-bacterial community composition shifted mainly along the easily oxidizable carbon (EOC) arrows following straw amendment among four different soil organic carbon fractions, suggesting that increased EOC was the main driver of alerted denitrifying bacterial community composition. This study revealed straw return suppressed N2O emission via altering denitrifying bacterial community compositions and highlighted the importance of EOC in controlling denitrifying bacterial communities.

Decreased IL-6 induces sensitivity of hepatocellular carcinoma cells to sorafenib.

Sorafenib has been recommended as a new palliative therapy for advanced hepatocellular carcinoma (HCC). However, the sensitivity of HCC cells to sorafenib is declined along with the extension of medication time, and the clinical outcome varies with patients receiving sorafenib therapy. Therefore, in the present study, we attempted to investigate the effect and mechanisms of IL-6 on sensitivity of HCC cells to sorafenib regarding the cell proliferation and apoptosis. Tissues from patients with HCC and its paracarcinoma tissues were collected for IL-6 expression determination. SiRNA (si) IL-6 was transfected into SMMC-7721 cells to evaluate the effects of IL-6 on cell sensitivity to sorafenib by RT-PCR, western blot, CCK-8 and flow cytometry assay. Results indicated that IL-6 was significantly upregulated in tumor tissues than that of paracarcinoma tissues. Furthermore, sorafenib significantly inhibited cell proliferation, IL-6 level and activation of p-PI3K/AKT while promoted the cell apoptosis rate and Caspase3 level compared as the control group, which were further promoted by administration of si IL-6. Therefore, downregulating IL-6 could be a potential treatment to increase the cell sensitivity of HCC cells to sorafenib.