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

Objective:To explore the predictive value of serum Dickkopf-related protein 1 (DKK1) and chemokine 21 (CCL21) expression for the pulmonary fibrosis progression in patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD).Methods:A prospective study method was used. One hundred and eight patients with RA-ILD (RA-ILD group) and 108 patients with simple rheumatoid arthritis (RA group) from September 2020 to July 2023 in Jincheng People's Hospital were selected. The patients with RA-ILD were treated with disease-modifying antirheumatic drugs and anti fibrotic drugs. Before treatment, the serum DKK1, CCL21, C-reactive protein (CRP), anti cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) salivary liquefied glycan antigen 6 (KL-6) were detected; the 28 joints disease activity score (DAS28) and Warrick score were assessed. The patients with RA-ILD were followed up for 1 year, and the occurrence of pulmonary fibrosis progression was recorded. The patients with pulmonary fibrosis progression were included in the progressive subgroup and vice versa in the stable subgroup. Multivariate Logistic regression was used to analyze the independent risk factors for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD. The predictive value of serum DKK1 and CCL21 for predicting the pulmonary fibrosis progression within 1 year in patients with RA-ILD was analyzed by receiver operating characteristic (ROC) curve. The decision curve of serum DKK1 and CCL21 to predict the pulmonary fibrosis progression within 1 year in patients with RA-ILD was plotted using the R language package.Results:The DKK1 in RA-ILD group was significantly lower than that in RA group: (76.02 ± 9.80) ng/L vs. (86.44 ± 9.26) ng/L, the CCL21 was significantly higher than that in RA group: (202.02 ± 25.86) ng/L vs. (172.42 ± 18.35) ng/L, and there were statistical differences ( P<0.01). The patients with RA-ILD were followed up for 1 year, 25 cases (23.15%) developed pulmonary fibrosis progression (progressive subgroup), and 83 cases did not develop pulmonary fibrosis progression (stable subgroup). The Warrick score, CCL21, ACPA and KL-6 in progressive subgroup were significantly higher than those in stable subgroup: (11.80 ± 3.56) scores vs. (7.75 ± 1.81) scores, (224.53 ± 27.26) ng/L vs. (195.25 ± 21.32) ng/L, (452.46 ± 38.35) kU/L vs. (414.37 ± 31.63) kU/L and (466.35 ± 42.32) kU/L vs. (416.82 ± 38.34) kU/L, the DKK1 was significantly lower than that in stable subgroup: (68.65 ± 8.24) ng/L vs. (78.24 ± 9.15) ng/L, and there were statistical differences ( P<0.01); there were no statistical differences in DAS28, RF, ERS and CRP between the two subgroups ( P>0.05). Multivariate Logistic regression analysis result showed that Warrick score, DKK1, CCL21, ACPA and KL-6 were independent risk factors for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD ( OR = 2.601, 0.752, 1.110, 1.062 and 1.038; 95% CI 1.227 to 5.517, 0.578 to 0.978, 1.019 to 1.209, 1.009 to 1.118 and 1.001 to 1.076; P<0.05). The ROC curve analysis result showed that the area under the curve of DKK1 and CCL21 for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD was 0.779 and 0.795, with optimal cutoff values of 74.750 and 207.615 ng/L. The area under the curve of DKK1 combined with CCL21 for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD was 0.873. The decision curve analysis result showed that the DKK1 combined with CCL21 for predicting pulmonary fibrosis progression within 1 year could improve the predictive value (the maximum benefit rate was 23.15%). Conclusions:Compared with RA patients, RA-ILD patients have decreased serum DKK1 levels and increased CCL21 levels. In patients with RA-ILD, the low expression of DKK1 and high expression of CCL21 are the risk factors of pulmonary fibrosis progression, and detecting serum levels of DKK1 and CCL21 can predict the risk of pulmonary fibrosis progression.

Objective:To explore the application of BOPPPS(Bridge-in,Objective,Pre-assessment,Participatory Learning,Post-assessment,Summary)combined with Direct Observation of Procedural Skills(DOPS)in anesthesiology teaching under the background of medical-educational collaboration.Methods:A total of 60 students majoring in anesthesiology were selected as the research objects.A total of 30 students in grade 2018 were enrolled in the control group and receired traditional teaching mode.A total of 30 students in grade 2019 were enrolled in the research group and received BOPPPS teaching mode.The assessment of the internship after graduation for both groups adopted the DOPS assessment mode.Two groups of students were subject to pre-enrollment assessment,including process evaluations,such as theoretical class attendance,classroom interaction,pre-test scores,post-test scores,and the final theoretical test score.A comprehensive evaluation of teachers'teaching effect was conducted.When the two groups were discharged from the department,in addition to the assessment of professional theoretical knowledge of anesthesia and the operation of conventional anesthesia skills,they also underwent nine DOPS assessments.Results:There was no statistical difference between the two groups in the attendance(P＞0.05).The classroom interaction,pre-test scores,post-test scores,final test scores and total test scores in the study group were higher than those in the control group(P＜0.05).In terms of comprehensive evaluation of teaching effect,there was no statistical difference between the two groups in the evaluation of teachers'teaching attitude(P＞0.05).However,the research group reported higher satisfaction in teaching skills,methods,student-teacher interaction,and classroom engagement(P＜0.05).Both the theoretical and practical scores in the research group were higher than those in the control group(P＜0.05).The DOPS assessment results showed that the research group was superior to the control group in terms of indication mastery,operation completion,teamwork and problem-solving ability,and comprehensive ability performance(P＜0.05).Conclusion:The application effect of BOPPPS combined with DOPS in anesthesiology teaching is better than the conventional teaching mode.

Objective To investigate the effect of esketamine on postoperative depression in frail elderly patients undergoing thoracoscopic radical resection of lung cancer.Methods A total of 88 frail elderly patients undergoing elective thoracoscopic radical resection of lung cancer were assigned randomly(using a randomization table)and in a double-blind way(blinding applies to both researchers and patients)to an esketamine group(Esk group,n=44)and a normal saline group(NS group,n=44).In the Esk group,0.25 mg/kg esketamine was injected intravenously during anesthesia induction,followed by continuous infusion of esketamine at 0.125 mg/kg per hour until 20 min before the end of surgery.In the NS group,equivalent volumes of normal saline were administered using the same method.The primary outcome was the score for the 17-item Hamilton Rating Scale for Depression(HAMD-17)on days 7 and 30 after surgery.The secondary outcomes included sleep quality and cognitive function.Sleep quality was assessed using the numerical rating scale(NRS)on days 1,3,and 7 after surgery and the Pittsburgh Sleep Quality Index(PSQI)on day 30 after surgery.Cognitive function was assessed using the Mini-Mental State Examination(MMSE)on days 1,3,7,and 30 after surgery.The other indicators included the levels of serum brain-derived neurotrophic factor(BDNF),5-hydroxytryptamine(5-HT),S100β protein,and neuron specific enolase(NSE)at 24 hours(T1),48 hours(T2),and 72 hours(T3)after surgery,as well as perioperative data and postoperative safety outcomes.Results Three patients were excluded from the Esk group and the NS group,respectively,and eventually,41 patients in each group were included in the statistical analysis.There were no statistically significant differences between the two groups in terms of age,sex,body mass index,American Society of Anesthesiologists(ASA)classification,comorbidities,educational attainment,and the scores for HAMD-17,PSQI,and MMSE 1 day before surgery(P＞0.05).Concerning the primary outcome,compared with those of the NS group,the HAMD-17 scores of patients in the Esk group were significantly lower at 7 days(median[P25,P75])(7[6,8]vs.7[6,12],P=0.045)and 30 days(6[6,7]vs.7[6,9],P=0.020)after surgery.Concerning the secondary outcomes,compared with those of the NS group,the sleep NRS scores of patients in the Esk group were significantly lower at 1,3,and 7 days after surgery(P＜0.01),and the MMSE scores were significantly higher(P＜0.05).Concerning the other indicators,compared with those of the NS group,the concentrations of serum BDNF and 5-HT in the Esk group were significantly higher(P＜0.05 or 0.01)at T1-T3,while the content of S100β was significantly lower(P＜0.01)at T1-T3;the levels of serum NSE were significantly lower at T1 and T2(P＜0.01);the consumption of propofol,sufentanil,remifentanil,and sevoflurane during surgery in the Esk group was significantly reduced(P＜0.05 or 0.01);the incidence of postoperative nausea/vomiting and hyperalgesia was significantly lower(P＜0.01);the duration of postoperative mechanical ventilation,length-of-stay in postanesthesia care unit(PACU),and postoperative length-of-stay in the hospital were significantly shorter(P＜0.01).Conclusion Esketamine can improve the postoperative depressive state,sleep quality,and cognitive function in frail elderly patients undergoing thoracoscopic radical resection of lung cancer.

Objective:To explore the application of BOPPPS(Bridge-in,Objective,Pre-assessment,Participatory Learning,Post-assessment,Summary)combined with Direct Observation of Procedural Skills(DOPS)in anesthesiology teaching under the background of medical-educational collaboration.Methods:A total of 60 students majoring in anesthesiology were selected as the research objects.A total of 30 students in grade 2018 were enrolled in the control group and receired traditional teaching mode.A total of 30 students in grade 2019 were enrolled in the research group and received BOPPPS teaching mode.The assessment of the internship after graduation for both groups adopted the DOPS assessment mode.Two groups of students were subject to pre-enrollment assessment,including process evaluations,such as theoretical class attendance,classroom interaction,pre-test scores,post-test scores,and the final theoretical test score.A comprehensive evaluation of teachers'teaching effect was conducted.When the two groups were discharged from the department,in addition to the assessment of professional theoretical knowledge of anesthesia and the operation of conventional anesthesia skills,they also underwent nine DOPS assessments.Results:There was no statistical difference between the two groups in the attendance(P＞0.05).The classroom interaction,pre-test scores,post-test scores,final test scores and total test scores in the study group were higher than those in the control group(P＜0.05).In terms of comprehensive evaluation of teaching effect,there was no statistical difference between the two groups in the evaluation of teachers'teaching attitude(P＞0.05).However,the research group reported higher satisfaction in teaching skills,methods,student-teacher interaction,and classroom engagement(P＜0.05).Both the theoretical and practical scores in the research group were higher than those in the control group(P＜0.05).The DOPS assessment results showed that the research group was superior to the control group in terms of indication mastery,operation completion,teamwork and problem-solving ability,and comprehensive ability performance(P＜0.05).Conclusion:The application effect of BOPPPS combined with DOPS in anesthesiology teaching is better than the conventional teaching mode.

Objective:To explore the predictive value of serum Dickkopf-related protein 1 (DKK1) and chemokine 21 (CCL21) expression for the pulmonary fibrosis progression in patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD).Methods:A prospective study method was used. One hundred and eight patients with RA-ILD (RA-ILD group) and 108 patients with simple rheumatoid arthritis (RA group) from September 2020 to July 2023 in Jincheng People's Hospital were selected. The patients with RA-ILD were treated with disease-modifying antirheumatic drugs and anti fibrotic drugs. Before treatment, the serum DKK1, CCL21, C-reactive protein (CRP), anti cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) salivary liquefied glycan antigen 6 (KL-6) were detected; the 28 joints disease activity score (DAS28) and Warrick score were assessed. The patients with RA-ILD were followed up for 1 year, and the occurrence of pulmonary fibrosis progression was recorded. The patients with pulmonary fibrosis progression were included in the progressive subgroup and vice versa in the stable subgroup. Multivariate Logistic regression was used to analyze the independent risk factors for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD. The predictive value of serum DKK1 and CCL21 for predicting the pulmonary fibrosis progression within 1 year in patients with RA-ILD was analyzed by receiver operating characteristic (ROC) curve. The decision curve of serum DKK1 and CCL21 to predict the pulmonary fibrosis progression within 1 year in patients with RA-ILD was plotted using the R language package.Results:The DKK1 in RA-ILD group was significantly lower than that in RA group: (76.02 ± 9.80) ng/L vs. (86.44 ± 9.26) ng/L, the CCL21 was significantly higher than that in RA group: (202.02 ± 25.86) ng/L vs. (172.42 ± 18.35) ng/L, and there were statistical differences ( P<0.01). The patients with RA-ILD were followed up for 1 year, 25 cases (23.15%) developed pulmonary fibrosis progression (progressive subgroup), and 83 cases did not develop pulmonary fibrosis progression (stable subgroup). The Warrick score, CCL21, ACPA and KL-6 in progressive subgroup were significantly higher than those in stable subgroup: (11.80 ± 3.56) scores vs. (7.75 ± 1.81) scores, (224.53 ± 27.26) ng/L vs. (195.25 ± 21.32) ng/L, (452.46 ± 38.35) kU/L vs. (414.37 ± 31.63) kU/L and (466.35 ± 42.32) kU/L vs. (416.82 ± 38.34) kU/L, the DKK1 was significantly lower than that in stable subgroup: (68.65 ± 8.24) ng/L vs. (78.24 ± 9.15) ng/L, and there were statistical differences ( P<0.01); there were no statistical differences in DAS28, RF, ERS and CRP between the two subgroups ( P>0.05). Multivariate Logistic regression analysis result showed that Warrick score, DKK1, CCL21, ACPA and KL-6 were independent risk factors for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD ( OR = 2.601, 0.752, 1.110, 1.062 and 1.038; 95% CI 1.227 to 5.517, 0.578 to 0.978, 1.019 to 1.209, 1.009 to 1.118 and 1.001 to 1.076; P<0.05). The ROC curve analysis result showed that the area under the curve of DKK1 and CCL21 for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD was 0.779 and 0.795, with optimal cutoff values of 74.750 and 207.615 ng/L. The area under the curve of DKK1 combined with CCL21 for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD was 0.873. The decision curve analysis result showed that the DKK1 combined with CCL21 for predicting pulmonary fibrosis progression within 1 year could improve the predictive value (the maximum benefit rate was 23.15%). Conclusions:Compared with RA patients, RA-ILD patients have decreased serum DKK1 levels and increased CCL21 levels. In patients with RA-ILD, the low expression of DKK1 and high expression of CCL21 are the risk factors of pulmonary fibrosis progression, and detecting serum levels of DKK1 and CCL21 can predict the risk of pulmonary fibrosis progression.

Objective To investigate the case characteristics of immune liver injury induced by camrelizumab,and to provide reference for clinical safety of drug use.Methods According to keywords,the case reports of immune liver injury induced by camrelizumab published from the establishment of the database to August 2023 were retrieved and screened,and the data were extracted and analyzed.Results A total of 12 literatures were selected,involving 12 patients,including 7 males and 5 females.Among them,age 43-76 years old,the average age was(62.92±10.19)years old,and most of them developed immune liver injury within 1 month.The primary diseases were all malignant tumors,and the main dosage of camrelizumab was 200mg intravenously,once every 3 weeks;The main immune liver injury was grade 3.After drug withdrawal and corresponding symptomatic treatment,the symptoms improved in 3 cases(25.00%),recovered in 5 cases(41.67%),and did not recover in 4 cases(33.33%).Conclusion Camrelizumab can cause immune liver injury,which can lead to death in severe cases.Therefore,clinical rational use of camrelizumab should be strengthened,the awareness of immune-related adverse events should be improved and pay attention to the immunological liver injury caused by camrelizumab.

Objective:To analyze the effect of dexmedetomidine combined with esketamine anesthesia on non-cardiac surgery for coronary heart disease and the effect on hemodynamics,stress response and postoperative complications of patients.Method:A total of 106 patients with coronary heart disease who were going to undergo laparoscopic abdominal surgery from Oct 2021 to Nov 2022 in our hospital were selected and randomly divided into the control group and the observation group,with 53 cases in each group.All patients underwent conventional surgical treatment.The control group was given dexmedetomidine anesthesia,while the observation group was given dexmedetomidine combined with esketamine anesthesia.The surgical indicators,incidence of postoperative complications,diastolic blood pressure(DBP),systolic blood pressure(SBP),pain visual analog scale(VAS),Ramsay sedation score,and the levels of oxide dismutase(SOD),malondialdehyde(MDA),cortisol(Cor)and blood glucose(GLU)were compared between the two groups.Results:There was no statistically significant difference in the operation time between the two groups(P＞0.05),but the postoperative sufentanil dosage of the observation group was lower than that of the control group,and the number of effective compressions was higher than that of the control group(P＜0.05).At 12 h postoperatively,there was no significant difference between the VAS score and Ramsay sedation score of the two groups(P＞0.05),and the VAS score and Ramsay sedation score in the observation group were better than those in the control group at 4 h and 8 h postoperatively(P＜0.05).The levels of MDA,GLU and Cor in both groups increased and the level of SOD decreased at 4 h postoperatively(P＜0.05),and the level of SOD in the observation group was higher than that of the control group,and the levels of MDA,GLU and Cor were lower than those of the control group(P＜0.05).Before anesthesia,there was no statisti-cally significant difference in hemodynamic indexes between the two groups(P＞0.05).Compared with before anesthesia,there were changes in HR,SBP,DBP,and RR of the two groups at the end of the operation and 24 h after the operation(P＜0.05),and the HR,SBP,DBP,and RR of the observation group were better than those of the control group(P＜0.05).The incidence of postoperative complications in the observation group was lower than that in the control group(P＜0.05).Conclusion:Dexmedetomidine combined with esketamine anesthesia can effectively stabilize the hemodynamics of patients,reduce postoperative stress response,and reduce postoperative complications.

Objective:To evaluate the in vitro cross-neutralization of serum antibodies in human and mice immunized with inactivated SARS-CoV-2 vaccine against Delta and Beta variants. Methods:Human serum samples after a second and a third dose of inactivated SARS-CoV-2 vaccine and mouse serum samples after a two-dose vaccination were collected. The neutralizing antibodies in the samples against SARS-CoV-2 strains of prototype, Delta and Beta variants were detected using micro-neutralization assay in biosafety level Ⅲ laboratory. The seroconversion rates and geometric mean titers (GMTs) of antibodies were calculated.Results:The seroconversion rates of antibodies in human serum samples against different SARS-CoV-2 strains were all above 95%. After two-dose vaccination, the GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 109, 41 and 15, respectively. The GMTs decreased by 2.7 folds and 7.3 folds for the Delta and Beta variants as compared with the prototype strain. After the booster vaccination, the GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 446, 190 and 86, respectively. The GMTs of neutralizing antibodies against Delta and Beta variants decreased by 2.3 folds and 5.2 folds as compared with that against the prototype strain. The seroconversion rates of antibodies against different SARS-CoV-2 strains in mouse serum samples were all 100%. The GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 2 037, 862 and 408, respectively. The GMTs decreased by 2.4 folds and 5.0 folds for the Delta and Beta variants.Conclusions:Inactivated SARS-CoV-2 vaccine could induce a certain level of neutralizing antibodies against Delta and Beta variants in both human and mouse models. Moreover, a third dose of vaccine induced higher levels of neutralizing antibodies against Delta and Beta variants in human. This study provided valuable data for the clinical application and protective evaluation of the inactivated SARS-CoV-2 vaccine.

Talaromyces Marneffei infection is rarely reported in patients with chronic active Epstein-Barr virus (EBV) infection. We reported an old man with chronic fever, pleomorphic rash, cough, EBV viraemia, and secondary hemophagocytic syndrome. Repeated histological biopsy and culture of skin lesions revealed Talaromyces Marneffei. This patient was diagnosed as chronic active EBV infection, and Talaromyces Marneffei infection. After treated with glucocorticoid steroids and anti-fungal therapy, the patient finally recovered. EBV infection is usually seen in immune compromised patients, who are susceptible to opportunistic pathogens rarely as Talaromyces Marneffei in this case.