Incremental Load Respiratory Muscle Training Improves Respiratory Muscle Strength and Pulmonary Function in Children with Bronchiectasis.

Methods: Participants underwent respiratory muscle training for 24 weeks. The main results were changes in respiratory muscle strength and pulmonary function indices (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow rate (PEF), forced expiratory flow 25-75% (FEF25-75%), and maximal midexpiratory flow 75/25 (MMEF75/25)) before, 12 weeks after, and 24 weeks after the intervention. The secondary outcomes were changes in the exercise load and work rate, exercise work, Leicester Cough Questionnaire (LCQ) scale, and Fatigue Severity Scale (FSS). Results: Compared with before the intervention, after 24 weeks of respiratory muscle training, the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were significantly enhanced (P < 0.05), while FVC, FEV1, and PEF were significantly increased (P < 0.01). FEF25-75 and MMEF75/25 values showed significant improvement compared to those before training (P < 0.05). The exercise loading, work, and exercise work rate of expiratory muscle training were significantly improved compared to those before intervention (P < 0.05). The LCQ score increased significantly (P < 0.001), and the FSS score decreased significantly (P < 0.001). Conclusion: Incremental load respiratory muscle training effectively improved children's lung function over the long term, improved the strength of their inspiratory and expiratory muscles, and improved their quality of life.

NUFIP1-engineered exosomes derived from hUMSCs regulate apoptosis and neurological injury induced by propofol in newborn rats.

BACKGROUND: Propofol can increase neurotoxicity in infants but the precise mechanism is still unknown. Our previous study revealed that nuclear FMR1 interacting protein 1 (NUFIP1), a specific ribophagy receptor, can alleviate T cell apoptosis in sepsis. Yet, the effect of NUFIP1-engineered exosomes elicited from human umbilical cord blood mesenchymal stem cells (hUMSCs) on nerve injury induced by propofol remains unclear. This study intended to investigate the effect of NUFIP1-engineered exosomes on propofol-induced nerve damage in neonatal rats. METHODS: Firstly, NUFIP1-engineered exosomes were extracted from hUMSCs serum and their identification was conducted using transmission electron microscopy (TEM), Flow NanoAnalyzer, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB). Subsequently, the optimal exposure duration and concentration of propofol induced apoptosis were determined in SH-SY5Y cell line using WB. Following this, we co-cultured the NUFIP1-engineered exosomes in the knockdown group (NUFIP1-KD) and overexpression group (NUFIP1-OE) with SH-SY5Y cells and assessed their effects on the apoptosis of SH-SY5Y cells using terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay, Hoechst 33258 staining, WB, and flow cytometry, respectively. Finally, NUFIP1-engineered exosomes were intraperitoneally injected into neonatal rats, and their effects on the learning and memory ability of neonatal rats were observed through the righting reflex and Morris water maze (MWM) test. Hippocampi were extracted from different groups for hematoxylin-eosin (HE) staining, immunohistochemistry, immunofluorescence, and WB to observe their effects on apoptosis in neonatal rats. RESULTS: TEM, Flow NanoAnalyzer, qRT-PCR, and WB analyses confirmed that the exosomes extracted from hUMSCs serum exhibited the expected morphology, diameter, surface markers, and expression of target genes. This confirmed the successful construction of NUFIP1-KD and NUFIP1-OE-engineered exosomes. Optimal exposure duration and concentration of propofol were determined to be 24 hours and 100 µg/ml, respectively. Co-culture of NUFIP1 engineered exosomes and SH-SY5Y cells resulted in significant up-regulation of pro-apoptotic proteins Bax and c-Caspase-3 in the KD group, while anti-apoptotic protein Bcl-2 was significantly decreased. The OE group showed the opposite trend. TUNEL apoptosis assay, Hoechst 33258 staining, and flow cytometry yielded consistent results. Animal experiments demonstrated that intraperitoneal injection of NUFIP1-KD engineered exosomes prolonged the righting reflex recovery time of newborn rats, and MWM tests revealed a significant diminution in the time and number of newborn rats entering the platform. HE staining, immunohistochemistry, immunofluorescence, and WB results also indicated a significant enhancement in apoptosis in this group. Conversely, the experimental results of neonatal rats in the OE group revealed a certain degree of anti-apoptotic effect. CONCLUSIONS: NUFIP1-engineered exosomes from hUMSCs have the potential to regulate nerve cell apoptosis and mitigate neurological injury induced by propofol in neonatal rats. Targeting NUFIP1 may hold great significance in ameliorating propofol-induced nerve injury.

H3K27ac-activated LncRNA NUTM2A-AS1 Facilitates the Progression of Colorectal Cancer Cells via MicroRNA-126-5p/FAM3C Axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are of great importance in the process of colorectal cancer (CRC) tumorigenesis and progression. However, the functions and underlying molecular mechanisms of the majority of lncRNAs in CRC still lack clarity. METHODS: A Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect lncRNA NUTM2A-AS1 expression in CRC cell lines. Cell counting kit 8 (CCK-8) assay and flow cytometry were used to examine the biological functions of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of CRC cells. RT-qPCR and western blot were implemented for the detection of cell proliferation-, apoptosis-related proteins, and FAM3C. Bioinformatics analysis and dual- luciferase reporter assays were utilized to identify the mutual regulatory mechanism of ceRNAs. RESULTS: lncRNA NUTM2A-AS1 notably elevated in CRC cell lines and the silencing of NUTM2A- AS1 declined proliferation and facilitated apoptosis. Mechanistically, NUTM2A-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) enriched at its promoter region, and NUTM2A-AS1 acted as a sponge for miR-126-5p, leading to the upregulation of FAM3C expression in CRC cell lines. CONCLUSION: Our research proposed NUTM2A-AS1 as an oncogenic lncRNA that facilitates CRC malignancy by upregulating FAM3C expression, which might provide new insight and a promising therapeutic target for the diagnosis and treatment of CRC.

Interaction analysis of high-risk pathological features on adjuvant chemotherapy survival benefit in stage II colon cancer patients: a multi-center, retrospective study.

BACKGROUND: We aimed to analyze the benefit of adjuvant chemotherapy in high-risk stage II colon cancer patients and the impact of high-risk factors on the prognostic effect of adjuvant chemotherapy. METHODS: This study is a multi-center, retrospective study, A total of 931 patients with stage II colon cancer who underwent curative surgery in 8 tertiary hospitals in China between 2016 and 2017 were enrolled in the study. Cox proportional hazard model was used to assess the risk factors of disease-free survival (DFS) and overall survival (OS) and to test the multiplicative interaction of pathological factors and adjuvant chemotherapy (ACT). The additive interaction was presented using the relative excess risk due to interaction (RERI). The Subpopulation Treatment Effect Pattern Plot (STEPP) was utilized to assess the interaction of continuous variables on the ACT effect. RESULTS: A total of 931 stage II colon cancer patients were enrolled in this study, the median age was 63 years old (interquartile range: 54-72 years) and 565 (60.7%) patients were male. Younger patients (median age, 58 years vs 65 years; P < 0.001) and patients with the following high-risk features, such as T4 tumors (30.8% vs 7.8%; P < 0.001), grade 3 lesions (36.0% vs 22.7%; P < 0.001), lymphovascular invasion (22.1% vs 6.8%; P < 0.001) and perineural invasion (19.4% vs 13.6%; P = 0.031) were more likely to receive ACT. Patients with perineural invasion showed a worse OS and marginally worse DFS (hazardous ratio [HR] 2.166, 95% confidence interval [CI] 1.282-3.660, P = 0.004; HR 1.583, 95% CI 0.985-2.545, P = 0.058, respectively). Computing the interaction on a multiplicative and additive scale revealed that there was a significant interaction between PNI and ACT in terms of DFS (HR for multiplicative interaction 0.196, p = 0.038; RERI, -1.996; 95%CI, -3.600 to -0.392) and OS (HR for multiplicative interaction 0.112, p = 0.042; RERI, -2.842; 95%CI, -4.959 to -0.725). CONCLUSIONS: Perineural invasion had prognostic value, and it could also influence the effect of ACT after curative surgery. However, other high-risk features showed no implication of efficacy for ACT in our study. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03794193 (04/01/2019).

Multidisciplinary discussion and management of synchronous colorectal liver metastases: A single center study in China.

BACKGROUND: The multidisciplinary team (MDT) has been carried out in many large hospitals now. However, given the costs of time and money and with little strong evidence of MDT effectiveness being reported, critiques of MDTs persist. AIM: To evaluate the effects of MDTs on patients with synchronous colorectal liver metastases and share our opinion on management of synchronous colorectal liver metastases. METHODS: In this study we collected clinical data of patients with synchronous colorectal liver metastases from February 2014 to February 2017 in the Chinese People's Liberation Army General Hospital and subsequently divided them into an MDT+ group and an MDT- group. In total, 93 patients in MDT+ group and 169 patients in MDT- group were included totally. RESULTS: Statistical increases in the rate of chest computed tomography examination (P = 0.001), abdomen magnetic resonance imaging examination (P = 0.000), and preoperative image staging (P = 0.0000) were observed in patients in MDT+ group. Additionally, the proportion of patients receiving chemotherapy (P = 0.019) and curative resection (P = 0.042) was also higher in MDT+ group. Multivariable analysis showed that the population of patients assessed by MDT meetings had higher 1-year [hazard ratio (HR) = 0.608, 95% confidence interval (CI): 0.398-0.931, P = 0.022] and 5-year (HR = 0.694, 95%CI: 0.515-0.937, P = 0.017) overall survival. CONCLUSION: These results proved that MDT management did bring patients with synchronous colorectal liver metastases more opportunities for comprehensive examination and treatment, resulting in better outcomes.

Factors associated with feeding behaviors among mothers of obese infants: a cross-sectional study.

Background: Infant obesity is a risk factor for diseases in childhood and even in adulthood. Maternal feeding behaviors are strongly associated with infant obesity, hence factors relevant to mother's perception, socioeconomic status, and social support that influence the feeding behaviors need to be explored. Therefore, this study aimed to examine associated factors of feeding behaviors among mothers with obese infants. Methods: This cross-sectional study was conducted at the pediatric wards of a tertiary hospital in Wenzhou, Zhejiang Province, China. Participants (n=134) were mothers of infant with obesity aged 6-12 months. Data were collected by structured questionnaires. Maternal feeding characteristics and the relationship between mothers' age, monthly personal income, parental self-efficacy, social support, benefits of maternal feeding behaviors, barriers to maternal feeding behaviors and feeding behaviors were examined. The Data was analyzed by descriptive statistics and multiple regression analysis. Results: Most of the infants (84.3%) was in the 98th-100th percentile. Nearly half of the mothers were 30-39 years old and unemployed (46.3%). One-third (61.40%) were multiparous mothers and 73.1% cared for their infants for more than 6 hours per day. Monthly personal income, parenting self-efficacy and social support together explained 28% of variance on feeding behaviors (P<0.05). Parenting self-efficacy (ß=0.309, P<0.05) and social support (ß=0.224, P<0.05) had significantly positive influence on feeding behaviors. Maternal personal income (ß=-0.196, P<0.05) had a significantly negative influence on feeding behaviors among mothers having infants with obesity. Conclusions: Nursing interventions should be focused on enhancing parenting self-efficacy and promoting social support for the feeding behaviors of mothers.

A comparison between knotted and knotless medial row of suture bridge technique in arthroscopic rotator cuff repair surgery: a meta-analysis.

BACKGROUND: The shoulder arthroscopic suture bridge technique is currently very popular, but scientific evidence relating to the clinical outcomes of the medial row with or without knots has not been systematic reviewed. PURPOSE: The purpose of this study was to compare the clinical outcomes of knotted versus knotless double-row suture bridges for rotator cuff repairs. STUDY DESIGN: Meta-analysis. METHOD: Five databases that contain literature in English were searched (Medline, PubMed, Embase, Web of Science, and the Cochrane Library), with a focus on works published between 2011 and 2022. Clinical data relating to arthroscopic rotator cuff repair with the suture bridge approach was examined and the outcomes of medial row knotting contrasted with that of the knotless technique. The search phrase used was: (double row) AND (rotator cuff) AND (repair), and the search method is subject term plus free word search. Literature quality evaluation was performed using the Cochrane "risk of bias" tool 1.0 and the Newcastle-Ottawa scale quality assessment instrument. RESULTS: One randomized controlled trial, four prospective cohort studies, and five retrospective cohort studies were included in this meta-analysis. Data pertaining to 1146 patients was drawn from these ten original papers and analyzed. Meta-analyses that were performed on 11 postoperative outcomes revealed that none of the differences were statistically significant (P > 0.05) and that the publications were unbiased (P > 0.05). Postoperative retear rate and postoperative retear categorization were the outcomes assessed. Scores on postoperative pain, forward flexion, abduction, and external rotation mobility were collated and evaluated. The University of California, Los Angeles scoring systems in the first year following surgery, the American Shoulder and Elbow Surgeons score and Constant scales in the first and second years after surgery were the secondary outcomes spotlighted in this study. CONCLUSION: The clinical outcomes of shoulder arthroscopic rotator cuff repair with the suture bridge technique with or without a knotted medial row was proven to be equivalent. These outcomes are about postoperative retear, postoperative retear classification, postoperative shoulder function score, postoperative shoulder mobility, and postoperative pain, respectively. It should be noted that the conclusions are based on short-term clinical follow-up data.

Deletion of DYRK1A Accelerates Osteoarthritis Progression Through Suppression of EGFR-ERK Signaling.

Dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) signaling is involved in the dynamic balance of catabolism and anabolism in articular chondrocytes. This study aimed to investigate the roles and mechanism of DYRK1A in the pathogenesis of osteoarthritis (OA). The expressions of DYRK1A and its downstream signal epidermal growth factor receptor (EGFR) were detected in the cartilage of adult wild-type mice with destabilized medial meniscus (DMM) and articular cartilage of patients with OA. We measured the progression of osteoarthritis in chondrocyte-specific knockout DYRK1A(DYRK1A-cKO) mice after DMM surgery. Knee cartilage was histologically scored and assessed the effects of DYRK1A deletion on chondrocyte catabolism and anabolism. The effect of inhibiting EGFR signaling in chondrocytes from DYRK1A-cKO mice was analyzed. Trauma-induced OA mice and OA patients showed downregulation of DYRK1A and EGFR signaling pathways. Conditional DYRK1A deletion aggravates DMM-induced cartilage degeneration, reduces the thickness of the superficial cartilage, and increases the number of hypertrophic chondrocytes. The expression of collagen type II, p-ERK, and aggrecan was also downregulated, and the expression of collagen type X was upregulated in the articular cartilage of these mice. Our findings suggest that DYRK1A delays the progression of knee osteoarthritis in mice, at least in part, by maintaining EGFR-ERK signaling in articular chondrocytes.

Cannabidiol regulates apoptosis and autophagy in inflammation and cancer: A review.

Cannabidiol (CBD) is a terpenoid naturally found in plants. The purified compound is used in the treatment of mental disorders because of its antidepressive, anxiolytic, and antiepileptic effects. CBD can affect the regulation of several pathophysiologic processes, including autophagy, cytokine secretion, apoptosis, and innate and adaptive immune responses. However, several authors have reported contradictory findings concerning the magnitude and direction of CBD-mediated effects. For example, CBD treatment can increase, decrease, or have no significant effect on autophagy and apoptosis. These variable results can be attributed to the differences in the biological models, cell types, and CBD concentration used in these studies. This review focuses on the mechanism of regulation of autophagy and apoptosis in inflammatory response and cancer by CBD. Further, we broadly elaborated on the prospects of using CBD as an anti-inflammatory agent and in cancer therapy in the future.

m6A regulator-mediated methylation modification patterns and immune microenvironment infiltration characterization in osteoarthritis.

Osteoarthritis (OA) is a common disease in orthopedics. RNA N6-methyladenosine (m6A) exerts an essential effect in a variety of biological processes in the eukaryotes. In this study, we determined the effect of m6A regulators in the OA along with performing the subtype classification. Differential analysis of OA and normal samples in the database of Gene Expression Omnibus identified 9 significantly differentially expressed m6A regulators. These regulators were monitored by a random forest algorithm so as to evaluate the risk of developing OA disease. On the basis of these 9 moderators, a nomogram was established. The results of decision curve analysis suggested that the patients could benefit from a nomogram model. The OA sample was classified as 2 m6A models through a consensus clustering algorithm in accordance with these 9 regulators. These 2 m6A patterns were then assessed with principal component analysis. We also determined the m6A scores for the 2 m6A patterns and their correlation with immune infiltration. The results indicated that type A had a higher m6A score than type B. Thus, we suggest that the m6A pattern may provide a new approach for diagnose and provide novel ideas for molecular targeted therapy of OA.

Publication trends and hotspots of drug resistance in colorectal cancer during 2002-2021: A bibliometric and visualized analysis.

Background: Chemotherapy, radiotherapy, targeted therapy and immunotherapy have demonstrated expected clinical efficacy, while drug resistance remains the predominant limiting factor to therapeutic failure in patients with colorectal cancer (CRC). Although there have been numerous basic and clinical studies on CRC resistance in recent years, few publications utilized the bibliometric method to evaluate this field. The objective of current study was to provide a comprehensive analysis of the current state and changing trends of drug resistance in CRC over the past 20 years. Methods: The Web of Science Core Collection (WOSCC) was utilized to extracted all studies regarding drug resistance in CRC during 2002-2021. CiteSpace and online platform of bibliometrics were used to evaluate the contributions of various countries/regions, institutions, authors and journals in this field. Moreover, the recent research hotspots and promising future trends were identified through keywords analysis by CiteSpace and VOSviewer. Results: 1451 related publications from 2002 to 2021 in total were identified and collected. The number of global publications in this field has increased annually. China and the USA occupied the top two places with respect to the number of publications, contributing more than 60% of global publications. Sun Yat-sen University and Oncotarget were the institution and journal which published the most papers, respectively. Bardelli A from Italy was the most prolific writer and had the highest H-index. Keywords burst analysis identified that "Growth factor receptor", "induced apoptosis" and "panitumumab" were the ones with higher burst strength in the early stage of this field. Analysis of keyword emergence time showed that "oxaliplatin resistance", "MicroRNA" and "epithelial mesenchymal transition (EMT)" were the keywords with later average appearing year (AAY). Conclusions: The number of publications and research interest on drug resistance in CRC have been increasing annually. The USA and China were the main driver and professor Bardelli A was the most outstanding researcher in this field. Previous studies have mainly concentrated on growth factor receptor and induced apoptosis. Oxaliplatin resistance, microRNA and EMT as recently appeared frontiers of research that should be closely tracked in the future.

Comprehensive analysis of the prognostic and immunotherapeutic implications of STAT family members in human colorectal cancer.

Background: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and the second leading cause of cancer mortality. Signal transducer and activator of transcription (STAT) proteins are a group of transcription factors implicated in cell signal transduction and gene transcription in several cancer types. However, the level of expression, genetic alterations, and biological function of different STATs, as well as their prognostic and immunotherapeutic value in CRC remain unclear. Methods: The mRNA and protein expression levels, genetic alterations, prognostic value, gene-gene and protein-protein interaction networks, and biological function of STATs in CRC were studied using the GEPIA, HPA, cBioPortal, PrognoScan, Kaplan-Meier plotter, GeneMANIA, STRING, and Metascape databases. The expression of STATs in CRC was confirmed using immunohistochemistry (IHC). Finally, the relationship between STAT expression and immune infiltration as well as immunotherapy-associated indicators was also investigated. Results: The expression levels of STAT2/5A/5B are downregulated in CRC, and the STAT1/3/4/5B expressions were significantly associated with the tumor stage of patients with CRC. The abnormal expression of STAT2/4/5B in patients with CRC is related to the prognosis of patients with CRC. The STATs and their neighboring proteins are primarily associated with lymphocyte activation, cytokine-mediated signaling pathways, positive regulation of immune response, regulation of cytokine production, and growth hormone receptor signaling pathways in cancer. The expression of STATs was significantly associated with immune infiltration and immunotherapy response-associated indicators. Conclusion: This study may help further understand the molecular mechanism of CRC and provide new prognostic biomarkers and immunotherapy targets in patients with CRC.

Photoactive terahertz metasurfaces for ultrafast switchable sensing of colorectal cells.

Metasurfaces with a strongly enhanced local field are envisioned as a powerful platform for ultrasensitive optical sensors to significantly amplify imperceptible differences between compatible bioanalytes. Through the use of phototunable silicon-based terahertz (THz) metasurfaces, we experimentally demonstrate ultrafast switchable sensing functions. It is found that the THz responses of the coupled-resonances in the metasurfaces shift from Lorentz-lattice mode to electromagnetism-induced transparency (EIT) mode under optical pumping within an ultrashort time of 32 ps, enabling an ultrafast sensitive sensor. For the Lorentz-lattice mode, the THz time-domain signal directly shows a highly sensitive response to detect tiny analytes without extra Fourier transformation as the mismatch between the two modes increases. Once the metasurfaces are switched to the EIT mode, the silicon-metal hybrid structure supports frequency-domain sensing ability due to strong field confinement with a sensitivity of 118.4 GHz/RIU. Both of the sensing configurations contribute to more subtle information and guarantee the accuracy of the sensor performance. Combined with the aforementioned advantages, the proposed metasurfaces have successfully identified colorectal cells between normal, adenoma, and cancer states in experiments. This work furnishes a new paradigm of constructing reliable and flexible metasurface sensors and can be extended to other optics applications.

Integrated analysis of intestinal microbiota and host gene expression in colorectal cancer patients.

Introduction. Colorectal cancer (CRC) is one of the most common cancers and poses heavy burden on global health. The relationship between mucosal microbiome composition and colorectal gene expression are rarely studied. In this study, we integrated transcriptome data with microbiome data to investigate the relationship between them in colorectal cancer patients.Gap statement. Previous studies have identified the contribution of gut microbiota and DEGs to the pathogenesis of CRC, but the relationship between mucosal microbiome composition and colorectal gene expression are rarely studied.Aim. In this study, we integrated transcriptome data with microbiome data to investigate the relationship between mucosal microbiome composition and colorectal gene expression.Methodology. First, three independent CRC gene expression profiles (GSE184093, GSE156355 and GSE146587) from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes (DEGs). Second, another dataset (GSE163366) was used to analyse gut mucosal microbiome differential abundance. GO (Gene Ontology) function and KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathway enrichment analyses of the DEGs were performed. Protein-protein interactions (PPIs) of the DEGs were constructed. The Spearman correlation analysis was computed between host DEGs and gut microbiome abundance data.Results. A total of 1036 upregulated DEGs and 1194 downregulated DEGs between noncancerous tissues and cancerous tissues were identified based on the analysis. One significant module with a score 37.65 was selected out via MCODE including 41 upregulated DEGs, which are were mostly enriched in two pathways, including microtubule binding and tubulin binding. In particular, significant negative correlations are prevalent between Fusobacterium and the 41 DEGs with the correlation ranging between -0.54 and -0.35, and there commonly exist significant positive correlations between Blautia and the 41 DEGs with the correlation ranging between 0.42 and 0.54, indicating that Fusobacterium and Blautia are two of the most important microbes interacting with the gene regulation.Conclusion. Our results demonstrate significant correlation between some gut microbes and DEGs, providing a comprehensive bioinformatics analysis of them for future investigation into the molecular mechanisms and biomarkers.

Correlation between apparent diffusion coefficient and tumor-stroma ratio in hybrid 18F-FDG PET/MRI: preliminary results of a rectal cancer cohort study.

Background: To explore possible correlations between the tumor-stroma ratio (TSR) and different imaging features of fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) in untreated rectal cancer patients. Methods: A patients with rectal cancer were included in this study. All participants were examined preoperatively with whole-body 18F-FDG PET/MRI. Two pathologists evaluated the TSR of tumors together. Apparent diffusion coefficient (ADC) values and PET-related parameters of the primary lesions were measured and compared between the stroma-high and stroma-low groups. Pearson's correlation or Spearman's rank correlation were used to evaluate the correlation between the ADC values, PET-related parameters, and pathological indices. Results: Our results showed that in the untreated rectal cancer patients, the ADC mean values correlated with the TSR (r=0.327; P=0.007), and stroma-high (low TSR) rectal cancer corresponded to relatively lower ADC mean values (813.54±88.68 vs. 879.92±133.18; P=0.018). The ADC mean and ADC minimum (ADCmin) values were found to be negatively correlated with the pathological T stages (r=-0.384, P=0.001; r=-0.416, P=0.001, respectively) as well as the largest tumor diameters (r=-0.340, P=0.005; r=-0.314, P=0.010, respectively) of rectal cancer. In addition, the pathological T stages correlated with all PET-related metabolic parameters, including mean standard uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) (r=0.338, P=0.006; r=0.350, P=0.004; r=0.326, P=0.007; and r=0.472, P<0.001, respectively). Our results also identified associations between the ADCmin values and SUVmean, SUVmax, and TLG (r=-0.335, P=0.006; r=-0.343, P=0.005; and r=-0.343, P=0.005, respectively). However, there were no statistical correlations between the PET/MRI parameters and the immunohistochemical (IHC) results. Conclusions: This study indicated that the intratumoral heterogeneity measured by PET/MRI may reflect characteristics of the tumor microenvironment. Hence, PET/MRI parameters might be helpful in predicting tumor aggressiveness and prognosis.

miR-887-3p Inhibits the Progression of Colorectal Cancer via Downregulating DNMT1 Expression and Regulating P53 Expression.

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide and the second leading cause of cancer-related deaths. Many researchers have reported that abnormal microRNAs (miRs) were expressed in CRC and participated in the occurrence and progression of CRC. However, there are few reports of miR-887-3p regulating CRC development. In the current study, we investigated the abnormal expression of miR-887-3p and also demonstrated its regulatory role and detailed molecular mechanism in CRC. Initially, miRNA expression data were obtained from TCGA-COAD that consisted of 453 CRC samples and 8 normal tissue samples. These were downloaded and analyzed to compare the expression level of miR-887-3p in CRC tissues to that in normal tissues. Moreover, 32 pairs of surgically resected CRC tumors and para-cancer tissues from our hospital were collected. Quantitative real-time PCR (qRT-PCR) was performed to detect miR-887-3p expression levels in CRC tissues, para-cancer tissues, several CRC cell lines, and an intestinal epithelial cell line. Following miR-887-3p mimic transfection in colon cancer SW480 cell line, the regulatory roles of miR-887-3p on cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) were detected through CCK-8, flow cytometry, transwell assay, and Western blot. After potential targeting protein was predicted by bioinformatic websites, the luciferase reporter assay and Western blot were used to confirm the target of miR-887-3p. The targeting protein expressions were detected by Western blot and qRT-PCR. The relationship between miR-887-3p level and the effect of miR-887-3p on P53 expression was evaluated by Western blot and qRT-PCR. The effects of miR-887-3p on CRC cell growth in vivo by xenograft tumor experiments were investigated, and Ki-67 in tumor tissue was determined by immunohistochemistry. Results. The COAD data demonstrated that the expression levels of miR-887-3p in CRC clinical sample tissues and cell line cultures were remarkably lower than para-cancer normal tissues and NCM460 cells (normal colonic epithelial cell line). Functional experiments demonstrated that overexpression of miR-887-3p in SW480 cells significantly reduced proliferation, migration, invasion, and EMT, and promoted cancer cell apoptosis. Additionally, Western blot, qRT-PCR, and luciferase reporter assays confirmed that DNMT1 was a downstream target of miR-887-3p. Moreover, the blocking of DNMT1 by miR-887-3p mimics also promoted P53 expression. Finally, overexpression of DNMT1 in SW480 cells could partially reverse the regulatory effect of miR-887-3p mimics on CRC cell development. From in vivo experiments, overexpression of miR-887-3p could inhibit tumor growth in CRC xenograft mice and reduce the Ki-67 level. Conclusion. The microRNA miR-887-3p is a potential biomarker of CRC. It inhibited CRC cell proliferation, invasion, and EMT, and promoted cell apoptosis through targeting and downregulating DNMT1 and promoting P53 expression. Therefore, miR-887-3p may be a good biomarker and therapeutic target for CRC treatment.

The effects of midazolam or propofol plus fentanyl on ICU mortality: a retrospective study based on the MIMIC-IV database.

Background: Patients in the intensive care unit (ICU) are often under stress and fail to cooperate well with invasive treatments. Analgesia and sedation are of great significance for reducing the suffering of patients and ensuring the application and effectiveness of treatment. For better clinical choice, we aimed to explore the effect of the combination of propofol + fentanyl or midazolam + fentanyl on the short-term prognosis of hospitalized patients in the ICU. Methods: According to the inclusion and exclusion criteria, we retrospectively included patients in the MIMIC-IV database receiving midazolam + fentanyl or propofol + fentanyl analgesic and sedative treatment using Structured Query Language (SQL) to extract clinical data from the MIMIC-IV database. The primary endpoint was the death rate within 28 days after the patient was admitted to the ICU. Doubly robust estimation was used to infer the relationship between sedation and analgesia and 28 days outcome. The gradient boosted model (GBM) was used to estimate the propensity score (PS) of the patient's sedation and analgesia program, PS was used as the weight, and the inverse probabilities weighting (IPW) model was used to generate a weighted cohort. Results: In total, 4,188 cases were included, with 2,174 (51.9%) in the propofol group and 2,014 (48.1%) in the midazolam group. In the PS score matching cohort, the 28-day mortality of patients in the midazolam group was 30.8%, and the 28-day mortality of patients in the propofol group was 25.5%. The adjusted odds ratio (OR) value was 1.421 [95% confidence interval (CI): 1.118-1.806, P<0.001]. Patients in the propofol group did not use vasoactive drugs for a longer period of time than the midazolam group, and patients in the propofol group received significantly more fluids than those in the midazolam group in the first three days after admission to the ICU. Conclusions: Compared with midazolam combined with fentanyl, propofol combined with fentanyl for sedation and analgesia can reduce the risk of short-term death in ICU patients.

Analysis of risk factors and prognosis of 253 lymph node metastasis in colorectal cancer patients.

BACKGROUND: This study aimed to explore potential risk factors for 253 lymph node metastasis, and to identify the prognostic impact of 253 lymph node metastasis in colorectal cancer patients. METHODS: A retrospective study was conducted of 391 colorectal cancer patients who underwent surgical treatments that included 253 lymph node dissection. Clinicopathological features, molecular indexes and 1-year overall survival rates were analyzed. RESULTS: Univariate analyses revealed the following risk factors for 253 lymph node metastasis: high preoperative levels of CEA, large tumour max diameters, and numbers of harvested lymph nodes, presence of vessel carcinoma emboli, low level of MSH6 and MLH1 immunohistochemical staining intensity. Multivariate analysis showed that elevated MLH1 immunohistochemical staining intensity was an independent protective factor for 253 lymph node metastasis (OR: 0.969, 95% CI 0.945, 0.994, P = 0.015). A significant difference was found in 1-year overall survival rate between 253 lymph node-positive and lymph node-negative colorectal cancer patients (88.9% vs.75.0%, P < 0.001). CONCLUSIONS: 253 lymph node-positive colorectal cancer patients had a worse prognosis than the 253 lymph node-negative patients. 253 lymph node dissection may improve the prognosis of colorectal cancer patients with high risk factors for 253 lymph node metastasis.

The effect of different inferior mesenteric artery ligation levels and different lymph node dissection areas on the short- and long-term outcomes of rectal cancer.

BACKGROUND: Surgery is the most effective treatment for rectal cancer patients, but its key steps, including selection of the level of inferior mesenteric artery ligation and removal of 253 lymph nodes, are still inconclusive. This study aimed to analyze the effects of different surgical methods, including levels of ligation (low vs. high) and lymph node dissection areas (D2 vs. D3) on the short-term and long-term outcomes. METHODS: Between March 2014 and August 2018, 253 rectal cancer patients were retrospectively analyzed; 113 patients underwent low ligation D2 lymph node dissection (LLD2), 75 patients underwent low ligation D3 lymph node dissection (LLD3), and 65 patients underwent high ligation (HL). We compared the short-term and long-term outcomes among the different groups. RESULTS: There were no significant differences among the groups in terms of the intraoperative variables, including operative time, blood transfusion, and conversion from laparoscopic to open surgery. The median blood loss was significantly lower in LLD3 (50 mL) than in LLD2 (100 mL) and HL (100 mL), but it was not significantly different between LLD2 and HL. There were no significant differences among the LLD2, LLD3, and HL groups in the incidence of postoperative complications (9.7% vs. 12.0% vs. 10.8%, respectively) and hospital stay (14 vs. 15 vs. 14, respectively). The anastomotic leakage Clavien-Dindo grade was significantly lower with LLD2 and LLD3 than with HL, but it was the same between LLD2 and LLD3. The total number of lymph nodes harvested in the LLD3 group (n=14) was higher than that in the LLD2 group (n=12), but it was not significantly different than that in the HL group (n=13). There were no significant differences among the groups in terms of 3-year overall survival rate and disease-free survival rate. CONCLUSIONS: Low ligation was similar to HL in terms of major intraoperative and postoperative parameters, but it can reduce the severity of anastomotic leakage to a certain extent. D3 lymph node dissection can increase the total number of lymph nodes harvested, but it did not improve long-term prognosis.

Effectiveness of using hydrocolloid dressing combined with 3M Cavilon No-Sting Barrier Film to prevent facial pressure injury on medical staff in a COVID-19 designated hospital in China: a self-controlled study.

BACKGROUND: COVID-19 is rapidly transmitted and has aroused enormous concern globally. This study aimed to investigate the effect of hydrocolloid dressing combined with 3M Cavilon No-Sting Barrier Film on the prevention of facial pressure injury in medical staff tasked with preventing and controlling COVID-19. METHODS: This was a self-controlled study. Medical staff who treated patients with COVID-19 infection in isolation wards from 6 January to 2 February, 2020, were selected to participate. Phase I was defined as the first 2 weeks of medical personnel entering the isolation ward, with phase II being the following 2 weeks. In phase I, medical workers only used hydrocolloid dressing on their faces, and in phase II, they used both hydrocolloid dressing and 3M Cavilon No-Sting Barrier Film. RESULTS: A total of 116 medical workers were selected as research subjects. The average facial local temperature in phase I was higher than that in phase II from the baseline (day 1) to the end of the study (day 14); however, there was no statistically significant difference (P>0.05). The incidence of facial pressure injury in phase II was lower than that in phase I (P<0.05); the facial skin comfort level among medical staff in phase II was higher than that in phase I (P<0.05). CONCLUSIONS: Hydrocolloid dressing combined with 3M Cavilon No-Sting Barrier Film for facial skin care can effectively reduce the incidence of facial pressure injury and can improve skin comfort level while ensuring isolation and a protective effect.