Objective To explore the prognostic value of glycolysis-related genes in colorectal cancer (CRC) patients and formulate a novel glycolysis-related prognostic risk model. Methods Single-cell and bulk transcriptomic data of CRC patients, along with clinical information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Glycolysis scores for each sample were calculated using single-sample Gene Set Enrichment Analysis (ssGSEA). Kaplan-Meier survival curves were generated to analyze the relationship between glycolysis scores and overall survival. Novel glycolysis-related subgroups were defined among the cell type with the highest glycolysis scores. Gene enrichment analysis, metabolic activity assessment, and univariate Cox regression were performed to explore the biological functions and prognostic impact of these subgroups. A prognostic risk model was built and validated based on genes significantly affecting the prognosis. Gene Set Enrichment Analysis (GSEA) was conducted to explore differences in biological processes between high- and low-risk groups. Differences in immune microenvironment and drug sensitivity between these groups were assessed using R packages. Potential targeted agents for prognostic risk genes were predicted using the Enrichr database. Results Tumor tissues showed significantly higher glycolysis scores than normal tissues, which was associated with a poor prognosis in CRC patients. The highest glycolysis score was observed in epithelial cells, within which we defined eight novel glycolysis-related cell subpopulations. Specifically, the P4HA1⁺ epithelial cell subpopulation was associated with a poor prognosis. Based on signature genes of this subpopulation, a six-gene prognostic risk model was formulated. GSEA revealed significant biological differences between high- and low-risk groups. Immune microenvironment analysis demonstrated that the high-risk group had increased infiltration of macrophages and tumor-associated fibroblasts, along with evident immune exclusion and suppression, while the low-risk group exhibited higher levels of B cell and T cell infiltration. Drug sensitivity analysis indicated that high-risk patients were more sensitive to Abiraterone, while low-risk patients responded to Cisplatin. Additionally, Valproic acid was predicted as a potential targeted agent. Conclusion High glycolytic activity is associated with a poor prognosis in CRC patients. The novel glycolysis-related prognostic risk model formulated in this study offers significant potential for enhancing the diagnosis and treatment of CRC.
Humans ; Colorectal Neoplasms/pathology* ; Glycolysis/genetics* ; Prognosis ; Transcriptome ; Tumor Microenvironment/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Kaplan-Meier Estimate

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

With the optimization of surgical technologies and postoperative management regimens, the number of lung transplantation has been significantly increased, which has become an important treatment for patients with end-stage lung disease. However, due to the impact of comprehensive factors, such as bronchial ischemia and immunosuppression, the incidence of airway stenosis after lung transplantation is relatively high, which severely affects postoperative survival and quality of life of lung transplant recipients. In recent years, with the improvement of perioperative management, organ preservation and surgical technologies, the incidence of airway stenosis after lung transplantation has been declined, but it remains at a high level. Early diagnosis and timely intervention play a significant role in enhancing clinical prognosis of patients with airway stenosis. In this article, the general conditions, diagnosis, treatment and prevention of airway stenosis after lung transplantation were reviewed, aiming to provide reference for comprehensive management of airway stenosis after lung transplantation and improving clinical prognosis of lung transplant recipients.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Objective:To investigate the risk factors for postoperative stiffness following rotator cuff repair and to develop a predictive risk assessment model.Methods:A retrospective analysis was conducted on 251 patients (111 males and 140 females) who underwent rotator cuff repair at the Department of Orthopedics, Civil Aviation General Hospital, from June 2016 to December 2022. Patients were divided into two groups based on the time of admission: the modeling group, comprising patients treated from June 2016 to June 2021, was used to construct the risk assessment model, while the validation group, including those treated from July 2021 to December 2022, was used to evaluate the model's effectiveness. In the modeling group, the incidence of postoperative stiffness one year after surgery was assessed. The study collected data on age, sex, body mass index, disease duration, smoking history, diabetes history, preoperative fat infiltration of the rotator cuff muscles, tear size, suturing technique, preoperative stiffness, re-tear rate, visual analogue scale (VAS) scores at two and six weeks postoperatively, Constant-Murley scores at six weeks postoperatively, and both preoperative and postoperative critical shoulder angle (CSA), acromial index (AI), and lateral acromion angle (LAA). Univariate analysis was used to identify potential risk factors for postoperative stiffness, followed by multivariate logistic regression to construct the risk assessment model. The validation group was used to reassess the identified risk factors.Results:Postoperative stiffness occurred in 21 out of 176 patients in the modeling group. Logistic regression analysis revealed that diabetes history, higher fat infiltration of the rotator cuff muscles, larger tear size, preoperative stiffness, higher VAS score at six weeks postoperatively, and lower Constant-Murley score at six weeks postoperatively were significant risk factors for postoperative stiffness. Based on the logistic regression model, a nomogram was created using R software. In the validation group, postoperative stiffness was observed in 11 out of 75 patients. The area under the ROC curve (AUC=0.926) indicated good discriminative ability in predicting postoperative stiffness. The goodness-of-fit test (H-L test: χ 2=2.215, P=0.947) demonstrated moderate calibration of the model. Conclusion:A history of diabetes, high fat infiltration of the rotator cuff muscles, large or massive rotator cuff tears, preoperative stiffness, higher VAS scores at six weeks postoperatively, and lower Constant-Murley scores at six weeks postoperatively are significant risk factors for postoperative stiffness after rotator cuff repair. The risk assessment model shows good discriminative power and calibration, making it a useful tool for predicting the risk of postoperative stiffness following rotator cuff repair.

Objective To summarize the best evidence of nutrition management in patients with severe pneumonia,aiming to offer evidence-based guidance for clinical healthcare professionals.Methods All evidence on nutrition management in patients with severe pneumonia was retrieved from various databases and websites including BMJ Best Practice,UpToDate,National Guideline Clearinghous(NGC),Guidelines International Network(GIN),Registered Nurses'Association of Ontario(RNAO),National Institute for Health and Care Excellence(NICE),Cochrane Library,OVID,PubMed,Embase,Web of Science,CINAHL,Chinese Medical Journal Full-text Database,CNKI,VIP,Wanfang,CBM,American Society for Parenteral and Enteral Nutrition(ASPEN),European Society for Clinical Nutrition and Metabolism(ESPEN),Society of Critical Care Medicine(SCCM)and European Society of Intensive Care Medicine(ESICM).The retrieved evidence included clinical decisions,guidelines,systematic reviews,expert consensuses and evidence summaries.The search period ranged from January 1st,2012 to December 31st,2022.There were 2 researchers who independently assessed the quality of the included studies and then extracted and summarized the evidence by topic.Results A total of 13 articles were involved,including 3 clinical decisions,4 guidelines,1 systematic review,and 5 expert consensuses.A total of 24 pieces of evidence were summarized across 6 aspects which encompassed team building,nutrition screening and assessment,nutritional requirements,nutrition intervention,nutrition monitoring,and health education.Conclusion The production process of this evidence summary followed standardized procedures,ensuring comprehensive content.Medical professionals should integrate clinical conditions,patient factors,and family preferences to select the most optimal evidence in order to enhance patient prognosis and improve medical quality.

Objective To analyze the influencing factors of aspiration risk in patients with acute poisoning during gastric lavage,and to build and validation a prediction model of aspiration risk in patients with acute poisoning during gastric lavage.Methods Through literature search and analysis,the risk factors of aspiration during gastric lavage was summarized in patients with acute poisoning.A retrospective study was conducted on patients with acute poisoning in the emergency department of a tertiary A general hospital in Ningbo from January 2020 to June 2023.Through R 4.2.1 and Python 3.11 programming language,the random forest,logistic regression,extreme gradient boosting tree and gradient boosting decision tree algorithms in machine learning were used to establish a prediction model of aspiration risk during gastric lavage in patients with acute poisoning and carry out internal verification.The prediction effects of the 4 prediction models were evaluated by confusion matrix,calibration curve,receiver operating characteristic curve,area under curve,Kolmogorov-Smirnov value,accuracy,precision,recall rate and F1 score,and the best model was selected.Results The modeling results of the 4 machine learning algorithms show that the area under the curve of the Random Forest,Logistic Regression,Extreme Gradient Boosting Tree,and Gradient Boosting Decision Tree algorithms are 0.954(0.934～0.974),0.878(0.843～0.913),0.910(0.880～0.939),and 0.917(0.889～0.945),respectively.The internal validation results show that the area under the curve of the random forest,logistic regression,extreme gradient boosting tree,and gradient boosting decision tree algorithms are 0.910(0.864～0.955),0.877(0.824～0.931),0.849(0.790～0.908),and 0.873(0.819～0.928),respectively.Age,state of consciousness,D-dimer and the time of absorption of poison are the 3 characteristics that are particularly prominent in the order of importance of the influencing factors of aspiration during gastric lavage in patients with acute poisoning.Conclusion Among the 4 prediction models,random forest model has better prediction effect,with good discrimination ability for the risk of aspiration during gastric lavage in patients with acute poisoning,and it is convenient for clinical use,which can provide references for medical staff to take preventive treatment and care.

Objective To analyze the causal relationship between gastroesophageal reflux disease (GERD) and chronic obstructive pulmonary disease (COPD) based on the bidirectional two-sample Mendelian randomization (MR). Methods Genetic variation information of GERD and COPD was obtained from Genome-Wide Association Studies (GWAS) and used as instrumental variables. Inverse variance-weighted (IVW), weighted median and MR-Egger methods were used for MR analysis, and sensitivity analysis was performed to validate the robustness of the results. Results A significant positive correlation was observed between genetically predicted GERD and the incidence risk of COPD, but there was no statistical association between COPD and the incidence risk of GERD. Positive IVW result showed that the odds ratio (OR) was 1.305 7, the 95% confidence interval (95%CI) was 1.114 4 to 1.529 8, and the P value was 0.000 9; the reverse IVW result showed that the OR was 0.982 3, the 95%CI was 0.917 4 to 1.051 9, and the P value was 0.610 4. Sensitivity analysis did not find any potential bias. Conclusion MR analysis shows that GERD is a risk factor for COPD, and treating GERD may help prevent or delay the progression of COPD.

Objective:To explore the correlation between the anatomical features of shoulder joint and the re-tear rate after surgical repair for small and medium-sized rotator cuff tears.Methods:From June 2017 to June 2019, 55 patients who were diagnosed with small or medium-sized rotator cuff tears and treated with arthroscopic single-row repair were enrolled. Demographics including age, sex, disease course, history of smoking and diabetes mellitus, re-tear rates, Constant-Murley score, University of California, Los Angeles score (UCLA) at 6-month, 1-year, 2-year and 3-year after operation were collected. Postoperative critical shoulder angle (CSA) and acromial index (AI) were measured and calculated based on CT scan. The patients were divided into two groups: patients who got re-tear history during follow-up were included into endpoint re-tear (ER) group, and those who got no re-tear history during follow-up were included into endpoint non-tear (EN) group. One-way Anova was used to compare the CSA\AI among different follow-up point. Fisher's exact test was used to compare sex, morbidity of smoking and diabetes between the ER and EN groups. Two independent samples t-test were used to compare age, disease course, CSA and AI at 1-day after operation, functional scores at each follow-up point between the two groups. Binomial logistic regression analysis was performed to test CSA and AI at 1-day after operation as the risk factors of rotator cuff re-tear at 6-month, 1-year, 2-year and 3-year after operation. The predictive efficacy of CSA and AI at 1-day after operation on re-tear rate at 3-year after operation were evaluated by receiver operating characteristic (ROC) curves, Pearson correlation analysis was used to evaluate the correlation between postoperative CSA/AI and postoperative functional recovery. Results:The CSA and AI of ER group were insignificantly different among all follow-up point ( P>0.05), the CSA and AI of EN group were significantly different among all follow-up point ( F=14.163, P<0.001; F=4.635, P<0.001). The re-tear rates at 6-month, 1-year, 2-year and 3-year after operation were 3.6%, 7.3%, 12.7%, 18.2%. The Constant-Murley score and UCLA scores of ER group at 3-year after operation were 93.60±2.84 and 32.30±1.49, respectively while in EN group, they were 92.11±4.10 and 33.18±1.27, respectively, there were no difference of the Constant-Murley score and UCLA score between ER and EN group at 3-year after operation ( P>0.05). CSA at 1-day after operation was the risk factor to re-tear at 1-year, 2-year and 3-year after operation [ OR=4.622, 95% CI (1.01, 21.06), P=0.048; OR=7.071, 95% CI (1.52, 32.87), P=0.013; OR=3.40, 95% CI (1.42, 8.12), P=0.006]. CSA and AI at 1-day after operation had certain predictive efficacy for rotator cuff re-tear at 3-year after rehabilitation, and CSA was more specific than AI, the optimal cutoff values of CSA and AI at 1-day after operation for predicting rotator cuff re-tear at 3-year after operation were 35.3°and 0.69, the AUC were 0.87 [ OR=3.40, 95% CI (1.42, 8.12), P<0.001]、0.77 [ OR=1.33, 95% CI (0.87, 2.02), P=0.008] respectively. CSA and AI had no relationship with postoperative functional recovery. Conclusion:Greater CSA and AI were predictive factors of small and medium-sized rotator cuff re-tear 1-3 years after surgery with CSA being more specific than AI. However, CSA and AI had no relationship with postoperative functional recovery.

Objective:To investigate the correlation between anatomical features of shoulder joint and postoperative stiffness after rotator cuff repair.Methods:212 patients diagnosed with rotator cuff injury undergoing rotator cuff repair in Civil Aviation General Hospital from March 2016 to December 2021 were enrolled. There were 97 male and 115 female with an average age of 58.87±9.69 years old (range, 41-72). The patients were divided into stiffness group (SG) and non-stiffness group (NG) according to the range of shoulder joint motion at 3-month after operation. Preoperative and postoperative joint anatomical features including critical shoulder angle (CSA), acromial index (AI), lateral acromion angle (LAA) were measured and calculated through CT scan and 3-dimension reconstruction. Age, sex, course of disease, body mass index, tendon fatty infiltration degree, type of rotator cuff injury according to DeOrio & Cofield classification, suture method, and preoperative and 3-month postoperative range of shoulder motion (flexion, abduction, and external rotation), preoperative stiffness condition were collected. All factors between two groups were compared, and binomial logistic regression analysis was performed to find out the risk factors of postoperative joint stiffness. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficacy of postoperative CSA, AI, and LAA for postoperative joint stiffness.Results:43 patients were enrolled in SG and 169 patients were enrolled in NG. Age, sex, course of disease, body mass index, tendon fatty infiltration degree, type of rotator cuff injury according to DeOrio & Cofield classification, suture method, and preoperative range of shoulder motion (flexion, abduction, and external rotation) between two groups were insignificantly different ( P>0.05). The ratio of patients with preoperative stiffness in SG is higher than that in NG (χ 2=40.38, P<0.001). Postoperative CSA and AI of SG were greater than those of NG ( t=5.44, P<0.001; t=4.89, P<0.001), and postoperative LAA of SG was smaller than that of NG group ( t=-5.86, P<0.001). Preoperative stiffness, large postoperative AI and small postoperative LAA were all risk factors of joint stiffness after rotator cuff suture [ OR=9.32, 95% CI(3.44, 25.27), P<0.001; OR=2.39, 95% CI(1.58, 3.62), P<0.001; OR=0.64, 95% CI(0.46, 0.91), P=0.012]. Postoperative CSA, AI and LAA had a certain predictive effect on postoperative joint stiffness (AUC>0.70). LAA was the most sensitive factor and CSA was the most specific factor. The optimal cutoff values of CSA, AI and LAA were 34.4°, 0.70 and 74.5° respectively, and the AUC for predicting postoperative joint stiffness were 0.76 [ OR=0.98, 95% CI(0.69, 0.84), P<0.001]、0.78[ OR=2.39, 95% CI(0.70, 0.84), P<0.001]、0.76[ OR=0.64, 95% CI(0.68, 0.83), P<0.001]. Conclusion:Postoperative CSA, AI and LAA had predictive efficacy on joint stiffness after rotator cuff repair. The greater postoperative CSA and AI or smaller postoperative LAA indicates increased risk of postoperative joint stiffness. LAA was the most sensitive factor and CSA was the most specific factor.