Objective:To investigate whether F.nucleatum affects the chemotherapy resistance of colorectal cancer by regulating ABC subfamily G subtype 2 (ABCG2), in view of the fact that the correlation between the two has not been reported. Methods:Oxaliplatin was used to interfere with colorectal cancer cells and co-cultured with F.nucleatum to establish a chemotherapy-induced model of microbial infection. Calcein AM/PI cell staining, trypan blue staining, and cell counting kit 8 (CCK-8) method were used to detect cell activity. Real-time fluorescence quantitative polymerase chain reaction and western blot were used to detect ABCG2 mRNA and protein expression levels in colorectal cancer cells. The target gene was knocked down by constructing shRNA plasmids. The HCT-116 cell F.nucleatum infection model was constructed and transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses were performed to determine the differential gene expression enrichment pathways. Genistein (GST) was used as an E-cadherin blocker, and triclabendazole sulfoxide (TCBZSO) was used as an ABCG2 blocker. Immunofluorescence was used to detect E-cadherin and β-catenin protein expressions and intracellular localization levels. The subcutaneous xenograft model of nude mice was constructed in vivo, and the expression level of ABCG2 protein in tissues was detected by immunohistochemical staining. Results:CCK-8 results showed that F. nucleatum+oxaliplatin group [HT-29, (92.26±1.66)%; HCT-116, (82.13±1.84)%] cell relative survival rate was higher than that of oxaliplatin group [HT-29, (79.64±3.72)%; HCT-116, (67.56±2.96)%; P＜0.001]. The relative survival rate of oxaliplatin and F. nucleatum co-culture group with ABCG2-knockdown HCT-116 cells [(61.44±1.48)%] was lower than that of F. nucleatum and oxaliplatin co-cultured with HCT-116 cells [(69.29±4.45)%, P=0.015]. GO enrichment analysis showed that HCT-116 cells co-cultured with F.nucleatum were significantly enriched in "β-catenin binding", "cadherin binding" and "regulation of Wnt signaling pathway". RT-qPCR results showed that the relative expression of ABCG2 mRNA in F.nucleatum + genistein group was significantly lower than that in F.nucleatum group ( P＜0.001). The results in vivo showed that the tumor weight in the F.n+L-OHP+TCBZSO group [(0.12±0.02)g] was lower than that in the F.n+L-OHP group [(0.33±0.05)g, P＜0.001]. Immunohistochemistry suggested that the promotion of ABCG2 protein expression by F. nucleatum was blocked after TCBZSO intervention. Conclusion:F. nucleatum up-regulates ABCG2 expression through E-cadherin/β-catenin signaling pathway to promote colorectal cancer resistance to oxaliplatin.

OBJECTIVE: To investigate the association between fluid balance trajectories within the first 3 days of intensive care unit (ICU) admission and 28-day mortality as well as the incidence of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients were extracted from the Medical Information Mart of Intensive Care-IV (MIMIC-IV). Group-based trajectory modeling (GBTM) was used to analyze the daily fluid balance of patients within 3 days of ICU admission, and grouping them accordingly. Univariate and multivariate Logistic regression analyses were performed to assess the association between fluid balance trajectory and 28-day mortality and ICU CRRT in SAP patients. RESULTS: A total of 251 SAP patients were included, with 33 deaths within 28 days, and a 28-day mortality of 13.15%; 49 patients (19.52%) continued to receive bedside CRRT after 3 days of ICU admission. The fluid balance on the 3rd day, cumulative fluid balance within 3 days of ICU admission, and incidence of CRRT in the death group were significantly higher than those in the survival group. According to GBTM groups, there were 127 cases in the moderate fluid resuscitation with rapid reduction (MF group), 44 cases in the large fluid resuscitation with rapid reduction (LF group), 20 cases in the moderate fluid resuscitation with slow reduction (MS group), and 60 cases in the small fluid resuscitation with slow reduction (SS group). The cumulative fluid balance within 3 days of ICU admission of the MF group, LF group, MS group, and SS group were 8.60% (5.15%, 11.70%), 16.70% (13.00%, 21.02%), 23.40% (19.38%, 25.45%), and 0.65% (-2.35%, 2.20%), respectively, and the incidence of CRRT during ICU hospitalization were 11.02%, 29.55%, 85.00%, and 8.33%, respectively, with statistically significant differences among the groups (both P < 0.05); the 28-day mortality were 11.02%, 18.18%, 20.00%, and 11.67%, respectively, with no statistically significant difference among the groups (P > 0.05). Kaplan-Meier survival curve analysis showed there was no statistically significant difference in 28-day cumulative survival rate among groups with different fluid balance trajectories (Log-rank test: χ ² = 2.31, P = 0.509). Multivariate Logistic regression analysis showed that cumulative fluid balance within 3 days of ICU admission was an independent risk factor for 28-day mortality [odds ratio (OR) = 1.071, 95% confidence interval (95%CI) was 1.005-1.144, P = 0.040] and CRRT requirement (OR = 1.233, 95%CI was 1.125-1.372, P < 0.001); early aggressive fluid resuscitation on day 1 reduced CRRT risk (OR = 0.866, 95%CI was 0.756-0.978, P = 0.030). CONCLUSIONS Dynamic fluid management is essential in SAP patients. While early aggressive fluid resuscitation may reduce CRRT demand, excessive cumulative fluid balance is associated with increased 28-day mortality and CRRT incidence.
Humans ; Male ; Female ; Middle Aged ; Water-Electrolyte Balance ; Continuous Renal Replacement Therapy ; Intensive Care Units ; Aged ; Adult ; Pancreatitis/mortality* ; Logistic Models ; Retrospective Studies ; Renal Replacement Therapy

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

[Purpose]To evaluate the liver and kidney safety of traditional Chinese medicine(TCM)compounds in the treatment of gastric cancer.[Methods]The clinical data of gastric cancer patients who attended in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2012 to February 2022 were collected.The results of liver and renal func-tion tests were rated according to National Cancer Institute-Common Terminology Criteria for Ad-verse Events(NCI-CTCAE)V5.0.The patients were divided into 4 groups:TCM group,TCM+chemotherapy/targeted/antivascular therapy group,TCM+TCM preparation group and TCM+chemotherapy/targeted/antivascular therapy+TCM preparation group,and the effects of TCM on liver and renal functions were analyzed.[Results]A total of 7 943 patients were included in the analysis,of which 2 941 cases receiving TCM ≥12 months,1 468 months ≥36 months,and 687 months≥60 months.The highest incidence rate of liver function abnormality was 13.71％,the highest in-cidence rate of grade 3/4 abnormality was 2.58％;the highest incidence of creatinine abnormality was 2.32％,the highest incidence rate of grade 3/4 abnormality was 0.37％in patients with differ-ent duration of taking TCM.Most of liver and renal function abnormalities occurred in the early stage of drug taking.The incidence of liver and renal function abnormalities in the TCM group was lower than that of the other three groups.The incidence of grade 3/4 abnormality for direct biliru-bin(DBIL)in the TCM group was 0.14％,for aspartate transaminase(AST)was 0.11％,for alka-line phosphatase(ALP)was 0.16％,for alanine aminotransferase(ALT)was 0.06％and for total bilirubin(TBIL)was 0.07％,and there was no grade 3/4 creatinine abnormality observed.The ab-normal liver and renal function indexes were not increased with the increase of the length of herbal medicine taking.[Conclusion]The study shows that long term taking TCM drugs and stan-dardized prescriptions for gastric cancer patients are safe.

[Purpose]To evaluate the liver and kidney safety of traditional Chinese medicine(TCM)compounds in the treatment of gastric cancer.[Methods]The clinical data of gastric cancer patients who attended in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2012 to February 2022 were collected.The results of liver and renal func-tion tests were rated according to National Cancer Institute-Common Terminology Criteria for Ad-verse Events(NCI-CTCAE)V5.0.The patients were divided into 4 groups:TCM group,TCM+chemotherapy/targeted/antivascular therapy group,TCM+TCM preparation group and TCM+chemotherapy/targeted/antivascular therapy+TCM preparation group,and the effects of TCM on liver and renal functions were analyzed.[Results]A total of 7 943 patients were included in the analysis,of which 2 941 cases receiving TCM ≥12 months,1 468 months ≥36 months,and 687 months≥60 months.The highest incidence rate of liver function abnormality was 13.71％,the highest in-cidence rate of grade 3/4 abnormality was 2.58％;the highest incidence of creatinine abnormality was 2.32％,the highest incidence rate of grade 3/4 abnormality was 0.37％in patients with differ-ent duration of taking TCM.Most of liver and renal function abnormalities occurred in the early stage of drug taking.The incidence of liver and renal function abnormalities in the TCM group was lower than that of the other three groups.The incidence of grade 3/4 abnormality for direct biliru-bin(DBIL)in the TCM group was 0.14％,for aspartate transaminase(AST)was 0.11％,for alka-line phosphatase(ALP)was 0.16％,for alanine aminotransferase(ALT)was 0.06％and for total bilirubin(TBIL)was 0.07％,and there was no grade 3/4 creatinine abnormality observed.The ab-normal liver and renal function indexes were not increased with the increase of the length of herbal medicine taking.[Conclusion]The study shows that long term taking TCM drugs and stan-dardized prescriptions for gastric cancer patients are safe.

Objective:To analyze the relationship between blood urea nitrogen (BUN)/albumin (ALB) ratio (B/A) and prognosis of patients undergoing percutaneous coronary intervention (PCI) guided by ultrasound before operation.Methods:A total of 116 patients who underwent PCI under the guidance of intra-coronary ultrasound in Xianyang Central Hospital from February 2020 to December 2022 were retrospectively selected as the observation group, and 120 healthy people in the same period were selected as the control group. All patients were followed up for 1 year after surgery, and 116 patients were divided into poor prognosis group ( n=33) and good prognosis group ( n=83), taking major adverse cardiovascular events (MACE) as the end point during follow-up. The levels of BUN and ALB in peripheral blood of all subjects were detected after admission, and B/A was calculated. The basic data, biochemical indexes and B/A of each group were analyzed and compared. The predictive value of preoperative BUN, ALB and B/A on postoperative MACE in patients with PCI guided by intra-coronary ultrasound was analyzed by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was used to evaluate the related influencing factors of postoperative MACE in patients with PCI guided by intra-coronary ultrasound. Results:The left ventricular end-diastolic inner diameter (LVEDD), N-terminal B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme (CK-MB), BUN and B/A in the observation group were higher than those in the control group, and left ventricular ejection fraction (LVEF) and ALB were lower than those in the control group (all P<0.05). NT-proBNP, CK-MB, BUN and B/A in the poor prognosis group were higher than those in the good prognosis group, and LVEF and ALB were lower than those in the good prognosis group (all P<0.05). ROC curve results showed that the AUC of peripheral blood BUN, ALB and B/A predicting postoperative MACE in patients with PCI guided by intra-coronary ultrasound were 0.833(95% CI: 0.783-0.883), 0.859(95% CI: 0.809-0.909) and 0.922(95% CI: 0.872-0.972). Multivariate logistic regression analysis showed that LVEF [ OR(95% CI)=1.952(1.317-2.895)], NT-proBNP [ OR(95% CI)=2.625(1.643-4.193)], BUN [ OR(95% CI)=3.353(1.922-5.851)], ALB [ OR(95% CI)=3.792(2.049-7.018)] and B/A [ OR(95% CI)=3.277(2.000-5.370)] were all the influencing factors of postoperative MACE in patients undergoing PCI guided by intra-coronary ultrasound ( P<0.05). Conclusions:The level of B/A in patients with PCI guided by intra-coronary ultrasound increased before surgery, and the high level of B/A is a risk factor for postoperative MACE, which can be used as a biological index to evaluate the postoperative MACE in patients with PCI guided by intra-coronary ultrasound.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Objective:To analyze the relationship between blood urea nitrogen (BUN)/albumin (ALB) ratio (B/A) and prognosis of patients undergoing percutaneous coronary intervention (PCI) guided by ultrasound before operation.Methods:A total of 116 patients who underwent PCI under the guidance of intra-coronary ultrasound in Xianyang Central Hospital from February 2020 to December 2022 were retrospectively selected as the observation group, and 120 healthy people in the same period were selected as the control group. All patients were followed up for 1 year after surgery, and 116 patients were divided into poor prognosis group ( n=33) and good prognosis group ( n=83), taking major adverse cardiovascular events (MACE) as the end point during follow-up. The levels of BUN and ALB in peripheral blood of all subjects were detected after admission, and B/A was calculated. The basic data, biochemical indexes and B/A of each group were analyzed and compared. The predictive value of preoperative BUN, ALB and B/A on postoperative MACE in patients with PCI guided by intra-coronary ultrasound was analyzed by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was used to evaluate the related influencing factors of postoperative MACE in patients with PCI guided by intra-coronary ultrasound. Results:The left ventricular end-diastolic inner diameter (LVEDD), N-terminal B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme (CK-MB), BUN and B/A in the observation group were higher than those in the control group, and left ventricular ejection fraction (LVEF) and ALB were lower than those in the control group (all P<0.05). NT-proBNP, CK-MB, BUN and B/A in the poor prognosis group were higher than those in the good prognosis group, and LVEF and ALB were lower than those in the good prognosis group (all P<0.05). ROC curve results showed that the AUC of peripheral blood BUN, ALB and B/A predicting postoperative MACE in patients with PCI guided by intra-coronary ultrasound were 0.833(95% CI: 0.783-0.883), 0.859(95% CI: 0.809-0.909) and 0.922(95% CI: 0.872-0.972). Multivariate logistic regression analysis showed that LVEF [ OR(95% CI)=1.952(1.317-2.895)], NT-proBNP [ OR(95% CI)=2.625(1.643-4.193)], BUN [ OR(95% CI)=3.353(1.922-5.851)], ALB [ OR(95% CI)=3.792(2.049-7.018)] and B/A [ OR(95% CI)=3.277(2.000-5.370)] were all the influencing factors of postoperative MACE in patients undergoing PCI guided by intra-coronary ultrasound ( P<0.05). Conclusions:The level of B/A in patients with PCI guided by intra-coronary ultrasound increased before surgery, and the high level of B/A is a risk factor for postoperative MACE, which can be used as a biological index to evaluate the postoperative MACE in patients with PCI guided by intra-coronary ultrasound.

Objective:To investigate whether F.nucleatum affects the chemotherapy resistance of colorectal cancer by regulating ABC subfamily G subtype 2 (ABCG2), in view of the fact that the correlation between the two has not been reported. Methods:Oxaliplatin was used to interfere with colorectal cancer cells and co-cultured with F.nucleatum to establish a chemotherapy-induced model of microbial infection. Calcein AM/PI cell staining, trypan blue staining, and cell counting kit 8 (CCK-8) method were used to detect cell activity. Real-time fluorescence quantitative polymerase chain reaction and western blot were used to detect ABCG2 mRNA and protein expression levels in colorectal cancer cells. The target gene was knocked down by constructing shRNA plasmids. The HCT-116 cell F.nucleatum infection model was constructed and transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses were performed to determine the differential gene expression enrichment pathways. Genistein (GST) was used as an E-cadherin blocker, and triclabendazole sulfoxide (TCBZSO) was used as an ABCG2 blocker. Immunofluorescence was used to detect E-cadherin and β-catenin protein expressions and intracellular localization levels. The subcutaneous xenograft model of nude mice was constructed in vivo, and the expression level of ABCG2 protein in tissues was detected by immunohistochemical staining. Results:CCK-8 results showed that F. nucleatum+oxaliplatin group [HT-29, (92.26±1.66)%; HCT-116, (82.13±1.84)%] cell relative survival rate was higher than that of oxaliplatin group [HT-29, (79.64±3.72)%; HCT-116, (67.56±2.96)%; P＜0.001]. The relative survival rate of oxaliplatin and F. nucleatum co-culture group with ABCG2-knockdown HCT-116 cells [(61.44±1.48)%] was lower than that of F. nucleatum and oxaliplatin co-cultured with HCT-116 cells [(69.29±4.45)%, P=0.015]. GO enrichment analysis showed that HCT-116 cells co-cultured with F.nucleatum were significantly enriched in "β-catenin binding", "cadherin binding" and "regulation of Wnt signaling pathway". RT-qPCR results showed that the relative expression of ABCG2 mRNA in F.nucleatum + genistein group was significantly lower than that in F.nucleatum group ( P＜0.001). The results in vivo showed that the tumor weight in the F.n+L-OHP+TCBZSO group [(0.12±0.02)g] was lower than that in the F.n+L-OHP group [(0.33±0.05)g, P＜0.001]. Immunohistochemistry suggested that the promotion of ABCG2 protein expression by F. nucleatum was blocked after TCBZSO intervention. Conclusion:F. nucleatum up-regulates ABCG2 expression through E-cadherin/β-catenin signaling pathway to promote colorectal cancer resistance to oxaliplatin.

Kawasaki disease is an acute, systemic vasculitis that easily injures coronary arteries and is the leading cause of acquired heart disease in children.Although the cause of Kawasaki disease remains unknown, it is widely believed that the pathogenesis of Kawasaki disease is an inflammatory cascade caused by a combination of infection and genetic predisposition.Regulatory T cells, which express Foxp3 + , CD4 + and CD25 + , are a T-cell subpopulation specialized in immune suppression.There are some correlations between regulatory T cells and Kawasaki disease in pathophysiology, treatment and prognosis.The dysfunction of regulatory T cells may be involved with the pathogenesis of Kawasaki disease, but there are few researches on it.This article reviews the progress of regulatory T cells in Kawasaki disease in recent years and summarizes the mechanism of regulatory T cells in the occurrence and repair of Kawasaki disease, prospecting the research future of targeted regulatory T cells therapy in the prevention of coronary artery lesions in Kawasaki disease.