Objective To identify genes of lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice base on bioinformatics and machine learning. Methods The acute lung injury dataset (GSE2411, GSE111241 and GSE18341) were download from the Gene Expression Database (GEO). Differential gene expression analysis was conducted. Gene ontology (GO) analysis, KEGG pathway analysis, GSEA enrichment analysis and protein-protein interaction analysis (PPI) network analysis were performed. LASSO-COX regression analysis and Support Vector Machine Expression Elimination (SVM-RFE) was utilized to identify key biomarkers. Receiver operator characteristic curve was used to evaluate the diagnostic ability. Validation was performed in GSE18341. Finally, CIBERSORT was used to analyze the composition of immune cells, and immunocorrelation analysis of biomarkers was performed. Results A total of 29 intersection DEGs were obtained after the intersection of GSE2411 and GSE111241 differentially expressed genes. Enrichment analysis showed that differential genes were mainly involved in interleukin-17, cytokine - cytokine receptor interaction, tumor necrosis factor and NOD-like receptor signaling pathways. Machine learning combined with PPI identified Gpx2 and Ifi44 were key biomarkers. Gpx2 is a marker of ferroptosis and Ifi44 is an type I interferon-induced protein, both of which are involved in immune regulation. Immunocorrelation analysis showed that Gpx2 and Ifi44 were highly correlated with Neutrophils, TH17 and M1 macrophage cells. Conclusion Gpx2 and Ifi44 have potential immunomodulatory abilities, and may be potential biomarkers for predicting and treating ALI in mince.
ObjectiveTo evaluate the early effectiveness of local infiltration anesthesia (LIA) with compound betamethasone in total knee arthroplasty (TKA). MethodsThe clinical data of 102 patients with knee osteoarthritis who were treated by TKA and met the selection criteria between May 2022 and March 2023 were retrospectively analyzed. They were divided into control group and study group according to whether LIA preparation was added with compound betamethasone, with 51 cases in each group. There was no significant difference of baseline data, such as age, gender, body mass index, operative side, preoperative range of motion (ROM), Knee Society Score (KSS), white blood cell (WBC), and hematocrit between the two groups (P>0.05). The intraoperative total blood loss and hidden blood loss were recorded, and WBC was recorded on the 1st, 2nd, and 3rd days after operation. Pain was assessed by visual analogue scale (VAS) score on the 1st, 2nd, and 3rd days after operation and morphine intake milligrames equivalent within 48 hours after operation. Passive ROM, maximum extension and flexion angles of knee joint were measured on the 3rd day after operation; the early postoperative complications were recorded. ResultsThere was no significant difference in total blood loss and hidden blood loss between the two groups (P>0.05). The postoperative pain levels in both groups were relatively mild, and there was no significant difference in VAS scores in the first 3 days after operation and in morphine intake milligrams equivalent within 48 hours after operation between the two groups (P>0.05). The WBC in the first 3 days after operation was significantly improved in both groups (P<0.05). The WBC in the study group was significantly higher than that in the control group on the 1st and 2nd days after operation (P<0.05), but there was no significant difference between the two groups on the 3rd day after operation (P>0.05). On the 3rd day after operation, the maximum extension angle of knee joint in the study group was smaller than that in the control group, while the maximum flexion angle and passive ROM of knee joint in the study group were larger than those in the control group, and the differences were significant (P<0.05). There were 6 cases of fever and 17 cases of deep venous thrombosis in the control group, and 1 case and 14 cases in the study group, respectively. There was no poor wound healing and periprosthetic joint infection in the two groups, and there was no significant difference in the incidence of complications between the two groups (P>0.05). ConclusionThe application of compound betamethasone in LIA during TKA is a safe and optimal strategy to promote the early postoperative rehabilitation of patients.
ObjectiveTo study the infiltration situation of breast cancer surface skin, and explore the characteristics of infiltration of breast cancer surface skin at the molecular level. MethodsNested reverse transcription-polymerase chain reaction technique was used to detect the expressions of human mammaglobin(hMAM)mRNA in 15 cases of hyperplasia of mammary gland tissues, 15 cases of breast fibroadenoma tissues, and 60 cases of breast cancer tissues and their corresponding tumor surface skins. The relationship of the hMAM mRNA expression in the surface skins of breast cancer tissue to its clinicopathologic characteristics was analyzed. ResultsThe hMAM mRNA positive expressions in the breast fibroadenoma tissues, hyperplasia of mammary gland tissues, and breast cancer tissues were 40.00%(6/15), 53.33%(8/15), and 83.33%(50/60), respectively, which in the breast cancer tissues was significantly higher than that in the breast fibroadenoma tissues or hyperplasia of mammary gland tissues(P < 0.05). There was no hMAM mRNA positive expression in the surface skin of fibroadenoma or hyperplasia of mammary gland tissues, but there was 3(5.00%)cases of the hMAM mRNA positive expressions in the breast cancer surface skin. The hMAM mRNA positive expression in the breast cancer surface skin was not related with the patient age, tumor diameter, and tumor staging(P > 0.05), but was related with axillary lymph nodes metastasis and distance from tumor to nipple less than 4 cm(P < 0.05). ConclusionsThe hMAM mRNA highly expresses in breast cancer tissue and it has a certain value in the diagnosis of infiltration of breast cancer surface skin. The patients with axillary lymph node metastasis and distance from tumor to nipple less than 4 cm are more susceptible to infiltration of breast cancer surface skin.
ObjectiveA prospective randomized controlled study was conducted to investigate the early postoperative analgesic effectiveness of using liposomal bupivacaine (LB) for local infiltration anesthesia (LIA) in unicompartmental knee arthroplasty (UKA). Methods Between January 2024 and July 2024, a total of 80 patients with knee osteoarthritis (KOA) who met the selection criteria were enrolled in the study. Patients were randomly assigned to either the LB group or the “cocktail” group in a 1∶1 ratio using a random number table, with 40 patients in each group. Baseline characteristics, including gender, age, body mass index, operated side, Kellgren-Lawrence grade, and preoperative American Society of Anesthesiologists (ASA) classification, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee joint range of motion, showed no significant difference between the two groups (P>0.05). Both groups received LIA and comprehensive pain management. The surgical duration, incision length, pain-related indicators [resting and activity visual analogue scale (VAS) scores, total dosage of oral morphine, WOMAC scores], knee joint range of motion, first ambulation time after operation, length of hospital stay, and postoperative adverse events. ResultsThere was no significant difference between the two groups in surgical duration, incision length, first ambulation time after operation, length of hospital stay, total dosage of oral morphine, and pre-discharge satisfaction with surgery and WOMAC scores (P>0.05). At 4, 12, and 24 hours after operation, the resting and activity VAS scores in the “cocktail” group were lower than those in the LB group; at 60 and 72 hours postoperatively, the resting VAS scores in the LB group were lower than those in the “cocktail” group, with the activity VAS scores also being lower at 60 hours; all showing significant differences (P<0.05). There was no significant difference in the above indicators between the two groups at other time points (P>0.05). On the second postoperative day, the sleep scores of the LB group were significantly higher than those of the “cocktail” group (P<0.05), while there was no significant difference in sleep scores on the day of surgery and the first postoperative day (P>0.05). Additionally, the incidence of complications showed no significant difference between the two groups (P>0.05). ConclusionThe use of LB for LIA in UKA can provide prolonged postoperative pain relief; however, it does not demonstrate a significant advantage over the “cocktail” method in terms of short-term analgesic effects or reducing opioid consumption and early functional recovery after UKA. Nevertheless, LB may help reduce postoperative sleep disturbances, making it a recommended option for UKA patients with cardiovascular diseases and insomnia or other mental health issues.
ObjectiveTo evaluate the impact of local infiltration analgesia on postoperative pain after hip arthroplasty. MethodsRelevant randomized controlled trials comparing the analgesia effect and adverse effects between local infiltration analgesia group and non-local infiltration analgesia group (control group) were identified from Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, VIP database and Wanfang database from their establishment until May 2016. A systematic review was performed to compare the pain scores and adverse events between those two groups. Effective data were pooled for Meta-analysis with software RevMan 5.2.0. ResultsTwelve eligible trials were identified in this study. The pain scores of the two groups of patients during rest time after surgery were significantly different[WMD=-19.06, 95%CI (-21.51, -16.62), P<0.000 01]; the pain scores were also significantly different during activity time[WMD=-11.45, 95%CI (-15.56, -7.34), P<0.000 01]. There was significant difference in postoperative nausea and vomiting between the two groups[RR=0.59, 95%CI (0.42, 0.84), P=0.003]. The pain degree and incidence of nausea and vomiting in the local infiltration analgesia group were lower than the control group, but there was no significant difference between the two groups in terms of urinary retention, itch and hypotension (P>0.05). ConclusionLocal infiltration analgesia is effective in reducing postoperative pain without any additional adverse reactions.
ObjectiveTo establish and validate the diagnostic model of ferroptosis genes for acute myocardial infarction (AMI) based on bioinformatics. MethodsFive AMI gene expression data were obtained from Gene Expression Omnibus (GEO), namely GSE66360, GSE48060, GSE60993, GSE83500, GSE34198. Among them, GSE66360 was used as the training set to perform differential analysis, and intersection of differential genes and ferroptosis genes was taken to obtain differentially expressed ferroptosis genes in AMI. GO and KEGG enrichment analysis was performed using Metascape website. Subsequently, random forest (RF) algorithm was used to screen out key genes with high classification performance according to the Keeny coefficient score, and artificial neural network (ANN) diagnostic model of AMI ferroptosis feature gene was constructed by model group GSE83500. The area under the receiver operating characteristic curve (AUC) of 10-fold cross-validation was used to evaluate the performance and generalization ability of the model, and 3 external independent datasets were used to verify the diagnostic performance of this model. The single sample gene setenrichment analysis was used to explore the difference in immune cell infiltration between infarcted myocardium and normal myocardium after AMI. In addition, correlation analysis between immune cells and key genes was also conducted. Finally, potential drugs that would prevent and treat AMI by regulating ferroptosis were screened out from the Coremin Medical platform. ResultsA total of 16 differentially expressed ferroptosis genes were obtained in the training set, GO enrichment analysis showed that they mainly participated in biological functions such as cellular response to biological stimuli and chemical stress, regulation of interleukin 17, etc. KEGG enrichment analysis showed that these genes were significantly enriched in NOD-like receptor signaling pathway, programmed cell necrosis, Leishmaniasis and other pathways. Four genes with good classification performance were screened out using RF algorithm, namely EPAS1, SLC7A5, FTH1, and ZFP36. The results of 10-fold cross-validation showed that the minimum AUC value was 0.746, the maximum value was 0.906, and the average value was 0.805. The AUC of the ANN model was 0.859, and the AUC values of the three independent validation sets were 0.763 (GSE48060), 0.673 (GSE60993), 0.698 (GSE34198). Immune cell infiltration found that macrophages, mast cells and monocytes were significantly active after AMI. Correlation analysis found that there were positive correlations between 4 key genes and activated dendritic cells, eosinophils and γδT cells. A total of 20 potential western medicines were predicted which could prevent and treat AMI by regulating ferroptosis, and the predicted potential Chinese medicine was mainly heat-clearing and detoxifying and blood-activating and removing blood stasis drugs. ConclusionThe identified AMI ferroptosis genes by bioinformatics method have certain diagnostic significance, which provides a reference for disease diagnosis and treatment.
Objective To analyze the relationship between the expression of carbonic anhydrase 3 (CA3) in breast cancer tissues, its prognostic potential and the number of immune cells by a variety of online databases. Methods GEPIA2.0 and TIMER databases were used to analyze the difference of CA3 mRNA expression in breast cancer tissues. Bc-GenExMinerv4.7 database was used to analyze the difference of CA3 mRNA expression in breast cancer subcategories. Kaplan-Meier plotter, Bc-GenExMinerv4.7 and PrognoScan databases were used to analyze the effect of CA3 mRNA expression levels on prognosis of patient. LinkedOmics database was used to analyze of the biological behavior involved in CA3 co-expressed genes. TIMER database was used to analyze the relationship between CA3 mRNA expression and immune cells infiltration in breast cancer tissues. Results The expression of CA3 mRNA in breast cancer tissues was lower than that in normal breast tissues (P<0.05), and the expression levels of CA3 mRNA were higher in ER negative (P<0.05), PR negative (P<0.05), HER2 negative (P<0.05) and no lymphatic metastasis (P<0.05). In addition, the expression level of CA3 in breast cancer patients with high Ki67 expression was lower (P<0.05) and closely related to SBR and NPI grade (P<0.05). Breast cancer patients with low expression of CA3 mRNA had lower overall survivall, recurrence free survival, and disease free survival ( P<0.05). Ten of the top 50 positively correlated co-expressed genes screened out had low risk ratio (P<0.05), and 11 of the top 50 negatively correlated co-expressed genes screened out had high risk ratio (P<0.05). The expression of CA3 mRNA was positively correlated with CD4+ T cells and CD8+ T cells in breast cancer tissues (rs=0.175, P<0.001; rs=0.137, P<0.001), and negatively correlated with T cell failure markers LAG3, TIM-3 and PVRL2 (rs=–0.100, P<0.01; rs=–0.143, P<0.001; rs=–0.082, P<0.05). Conclusions The low expression of CA3 mRNA in breast cancer tissues is correlated with the occurrence, development and prognosis of breast cancer. CA3 can be used as a potential independent prognostic marker for breast cancer and may be related to immune infiltration.
Objective To compare the early analgesic effects and the impact on knee joint function recovery after unicompartmental knee arthroplasty (UKA) between single adductor canal block (SACB) and continuous adductor canal block (CACB) combined with local infiltration anesthesia (LIA) using a prospective study. Methods The patients with knee osteoarthritis admitted between April 2022 and December 2023 were enrolled as a subject. Among them, 60 patients met the selection criteria and were enrolled in the study. They were randomly assigned to the SACB group or CACB group in a ratio of 1:1 using a random number table method. There was no significant difference between the two groups (P>0.05) in terms of age, gender, height, body mass, body mass index, affected side, and preoperative resting visual analogue scale (VAS) score and active VAS score, Oxford knee score (OKS), and American Hospital of Special Surgery (HSS) score. All patients received multimodal analgesia management using LIA combined with SACB or CACB. The operation time, pain related indicators (resting and activity VAS scores, number and timing of breakthrough pain, opioid consumption), joint function related indicators (quadriceps muscle strength, knee range of motion, OKS score, and HSS score), as well as postoperative block complications and adverse events were recorded and compared between the two groups. Results There was no significant difference in the operation time between the two groups (P<0.05). All patients in the two groups were followed up with a follow-up time of (9.70±4.93) months in the SACB group and (12.23±5.05) months in the CACB group, and the difference was not significant (P>0.05). The CACB group had a significant lower resting VAS score at 24 hours after operation compared to the SACB group (P<0.05). There was no significant difference in resting and active VAS scores between the two groups at other time points (P>0.05). The CACB group had a significantly lower incidence of breakthrough pain compared to the SACB group [9 cases (30.00%) vs. 17 cases (56.67%); P<0.05). However, there was no significant difference in the timing of breakthrough pain occurrence and opioid consumption between the two groups (P>0.05). Four cases in the SACB group and 7 cases in the CACB group experienced adverse events, with no significant difference in the incidence of adverse events between the two groups (P>0.05). The CACB group had significantly better knee joint mobility than the SACB group at 1 and 2 days after operation (P<0.05). There was no significant difference between the two groups in knee joint mobility on 0 day after operation and quadriceps muscle strength and OKS and HSS scores at different time points (P>0.05). Conclusion In UKA, the analgesic effects and knee joint function recovery are similar when compared between LIA combined with SACB and LIA combined with CACB. However, SACB is simpler to perform and can avoid adverse events such as catheter displacement and dislocation. Therefore, SACB may be a better choice.
Objectives To overview the systematic reviews/meta-analyses of safety of femoral nerve block (FNB) used as a postoperative analgesic technique in patients undergoing total knee arthroplasty (TKA). Methods We searched databases including The Cochrane Library, PubMed, EMbase, CNKI, WanFang Data, and VIP from inception to July, 2016. Two reviewers independently screened literature, extracted data and used AMSTAR to evaluate the methodological quality of the included studies. The major indexes used to evaluate the safety of FNB were the incidence rates of symptoms including nausea, vomiting, sedation, retention of urine, dizziness, pruritus, hypotension, falls, nenous thromboembolism and deep infection. Results A total of 12 systematic reviews/meta-analyses were included.They assessed the safety of FNB compared with local infiltration analgesia (LIA), periarticular multimodal drug injection (PMDI), epidural analgesia (EA), patient-controlled intravenous analgesia of opioids (PCA) and adductor canal block (ACB), respectively. The methodological quality of included studies were medium, with the scores between 3 to 10. The results of overview indicated that: FNB had lower incidence rates of nausea and vomiting compared with EA and PCA, but had higher than ACB. FNB had lower incidence rates of sedation and retention of urine compared with EA and PCA. FNB had lower incidence rates of dizziness compared with EA and PCA, and lower incidence rate of hypotension compared with EA. Conclusion Current evidence suggests that FNB is safer than EA and PCA. Due to the limited quantity and quality of the included studies, the above conclusions are needed to be verified by more high-quality studies.
Objective To investigate the relationship between the expression of mast cell expressed membrane protein 1 (MCEMP1) in gastric cancer and its relationship with prognosis and tumor immune infiltration. Methods Transcriptome expression profile data and clinical data information of gastric cancer and normal samples were downloaded from TCGA database, and differentially expressed genes in gastric cancer tumor microenvironment were extracted using R 4.0.5 software. Protein-protein interaction network of differentially expressed genes was constructed by using STRING online website, protein-protein interaction network and univariate Cox proportional hazards regression analysis were used for cross-tabulation analysis to obtain key genes. Kruskal-Wallis rank sum test was used to investigate the correlation between key genes and clinicopathological features. The possible signaling pathways involved in key genes were predicted by gene set enrichment analysis. We further analyzed the relationship between expression of key gene and the level of immune infiltration and immune molecules in gastric cancer by TISIDB online database and CIBERSORT algorithm. Results A total of 760 differentially expressed genes in gastric cancer were found and a key gene of MCEMP1 was derived from cross-tabulation analysis based on the results of protein-protein interaction network and univariate Cox proportional hazards regression analysis. Expression of MCEMP1 was significantly upregulated in gastric cancer tissues (P<0.001), and survival analysis showed that the overall survival rate of the group with high expression level of MCEMP1 was lower than that of low expression [HR=1.176, 95%CI (1.066, 1.297）, P=0.046]. Expression of MCEMP1 also correlated with age, T-stage, and clinical stage of gastric cancer (P<0.05) , and expression of MCEMP1 was significantly associated with a variety kinds of immune cells and expression of immune molecules (P<0.05). Conclusion MCEMP1 is a potential prognostic marker for gastric cancer and is associated with immune infiltration in gastric cancer.