Objective : To predict and validate key targets for cisplatin(DDP) resistance in colorectal cancer(CRC) to provide more options for precision medicine in clinical treatment. Methods: Differentially expressed genes(DEGs) between normal colonic mucosa and CRC were screened from the gene expression omnibus(GEO) database. Key genes were identified using the STRING database and Cytoscape software. DEGs were subjected to enrichment analysis using the gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) databases. Key targets were validated through RNA-seq, qRT-PCR, and Western blot. The versican(VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8, and cell viability was assessed using the CCK-8 assay. Flow cytometry was used to assess apoptosis and cell cycle distribution. qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes. Results : In this study, 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database. DEGs were mainly enriched in extracellular matrix degradation, extracellular matrix organization, and the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Based on protein-protein interaction network analysis, 20 hub genes were identified. By comparing the transcriptome sequencing results of the HCT8 parental strain and DDP-resistant strain, the VCAN gene was further selected. In CRC tissues, the expression level of VCAN was higher than that in normal colonic mucosa, and patients with high VCAN expression had shorter overall survival(OS) and recurrence free survival(RFS) times. Overexpression of VCAN in CRC cells promoted cell proliferation(P<0.05), increased resistance to DDP, reduced DDP-induced apoptosis(P<0.05), and G0/G1phase arrest(P<0.05); upregulation of VCAN activated the protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway. Conclusion Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC, potentially promoting CRC progression and DDP resistance by regulating the AKT-mTOR pathway.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To explore the mediating role of coping style and fear of disease progression between health literacy and self-management in postoperative chemotherapy patients with colorectal cancer. It provided a theoretical basis for improving the self-management ability of postoperative chemotherapy patients with colorectal cancer.Methods:Convenience sampling method was used to select postoperative chemotherapy patients with colorectal cancer admitted to the Second Affiliated Hospital of Anhui Medical University from October 2023 to May 2024, and a cross-sectional survey was conducted using Health Literacy Management Scale, Medical Coping Modes Scale, Fear of Progression Questionnaire-Short Form, and Cancer Patient Self-Management Assessment Scale.Results:A total of 229 questionnaires were distributed, of which 220 were returned as valid questionnaires, including 142 males and 78 females, aged (60.05 ± 10.14) years. The total health literacy score was (85.30 ± 9.45) points and self-management score was (150.36 ± 14.10) points among patients undergoing postoperative chemotherapy for colorectal cancer. Self-management was positively correlated with health literacy and facing ( r=0.576, 0.525, both P<0.01), while negatively correlated with avoidance, yielding, and fear of disease progression ( r=-0.660, -0.616, -0.566, all P<0.01). The mediation model showed that facing coping style and fear of disease progression had a chained mediation effect of 0.050 between health literacy and self-management, accounting for 8.36% of the total effect. Conclusions:Self-management in patients with postoperative chemotherapy for colorectal cancer was moderately low. The chain mediating role of coping style and fear of disease progression between health literacy and self-management in postoperative chemotherapy patients with colorectal cancer was established. Nursing staff should strengthen health education for postoperative chemotherapy patients with colorectal cancer, guide patients to face the disease positively, reduce fear, and promote patient self-management.

Objective:To compare the influence of definition methods of different isocenter on postoperative volumetric modulated arc therapy (VMAT) plans for patients with high-grade glioma (HGG),and to explore the feasibility of determining the treatment isocenter at location stage of computed tomography (CT) simulation system (CT-Sim). Methods:A total of 30 HGG patients who received radiotherapy after surgery in Peking University International Hospital from September 1,2021 to December 31,2022 were selected. 4 kinds of methods,which included center of mass (CT-COM) of target region of tumor bed was delineated by CT-Sim location stage,geometric center of target region of treatment plan system (TPS-Geo),whole brain geometric center of treatment plan system (TPS-Head) and center of mass of target region of TPS (TPS-COM),were respectively adopted to definite treatment isocenter for each patient,and they were respectively set as CT-COM group,TPS-Geo group,TPS-Head group and TPS-COM group to design 4 groups of VMAT treatment. The parameters included dose,conformity index (CI),uniformity index (HI) and machine unite (MU) among 4 groups of target region and organ at risk (OAR) were compared. Results:The doses of target region and OAR of four groups were similar,and all of them can meet the requirements of clinical dosimetry and clinical OAR dose limitation,without statistically significant differences (P>0.05). The covered volumes that brain tissues received 10,20,30,40 and 50 Gy doses in CT-COM group,TPS-Geo group and TPS-COM group closed to the maximum dose,the maximum dose of 2％ volume and mean dose (Dmax,D2％,Dmean) of brainstem,bilateral lens,optic chiasm,bilateral optic nerve and pituitary gland. The V10,V20,V30 of brain tissue,and Dmax,D2％,and Dmean of brainstem in TPS-Head group were slightly higher than those in other three groups,and the Dmean of lens,and Dmax,D2％ and Dmean of optic nerve at health side of TPS-Head group were slightly lower than those of other three groups,without statistically significant differences (P>0.05). Conclusion:The four VMAT plans of defining the treatment isocenter can meet the clinical dosimetric requirements,and can determine the isocenter at CT-Sim location stage,which can effectively avoid the occurrence of errors in the reduction of radiotherapy,and increase precision of delivery of radiotherapy dose,and enhance effective utilization rate of equipment.

Objective:To compare the influence of definition methods of different isocenter on postoperative volumetric modulated arc therapy (VMAT) plans for patients with high-grade glioma (HGG),and to explore the feasibility of determining the treatment isocenter at location stage of computed tomography (CT) simulation system (CT-Sim). Methods:A total of 30 HGG patients who received radiotherapy after surgery in Peking University International Hospital from September 1,2021 to December 31,2022 were selected. 4 kinds of methods,which included center of mass (CT-COM) of target region of tumor bed was delineated by CT-Sim location stage,geometric center of target region of treatment plan system (TPS-Geo),whole brain geometric center of treatment plan system (TPS-Head) and center of mass of target region of TPS (TPS-COM),were respectively adopted to definite treatment isocenter for each patient,and they were respectively set as CT-COM group,TPS-Geo group,TPS-Head group and TPS-COM group to design 4 groups of VMAT treatment. The parameters included dose,conformity index (CI),uniformity index (HI) and machine unite (MU) among 4 groups of target region and organ at risk (OAR) were compared. Results:The doses of target region and OAR of four groups were similar,and all of them can meet the requirements of clinical dosimetry and clinical OAR dose limitation,without statistically significant differences (P>0.05). The covered volumes that brain tissues received 10,20,30,40 and 50 Gy doses in CT-COM group,TPS-Geo group and TPS-COM group closed to the maximum dose,the maximum dose of 2％ volume and mean dose (Dmax,D2％,Dmean) of brainstem,bilateral lens,optic chiasm,bilateral optic nerve and pituitary gland. The V10,V20,V30 of brain tissue,and Dmax,D2％,and Dmean of brainstem in TPS-Head group were slightly higher than those in other three groups,and the Dmean of lens,and Dmax,D2％ and Dmean of optic nerve at health side of TPS-Head group were slightly lower than those of other three groups,without statistically significant differences (P>0.05). Conclusion:The four VMAT plans of defining the treatment isocenter can meet the clinical dosimetric requirements,and can determine the isocenter at CT-Sim location stage,which can effectively avoid the occurrence of errors in the reduction of radiotherapy,and increase precision of delivery of radiotherapy dose,and enhance effective utilization rate of equipment.

Objective:To explore the mediating role of coping style and fear of disease progression between health literacy and self-management in postoperative chemotherapy patients with colorectal cancer. It provided a theoretical basis for improving the self-management ability of postoperative chemotherapy patients with colorectal cancer.Methods:Convenience sampling method was used to select postoperative chemotherapy patients with colorectal cancer admitted to the Second Affiliated Hospital of Anhui Medical University from October 2023 to May 2024, and a cross-sectional survey was conducted using Health Literacy Management Scale, Medical Coping Modes Scale, Fear of Progression Questionnaire-Short Form, and Cancer Patient Self-Management Assessment Scale.Results:A total of 229 questionnaires were distributed, of which 220 were returned as valid questionnaires, including 142 males and 78 females, aged (60.05 ± 10.14) years. The total health literacy score was (85.30 ± 9.45) points and self-management score was (150.36 ± 14.10) points among patients undergoing postoperative chemotherapy for colorectal cancer. Self-management was positively correlated with health literacy and facing ( r=0.576, 0.525, both P<0.01), while negatively correlated with avoidance, yielding, and fear of disease progression ( r=-0.660, -0.616, -0.566, all P<0.01). The mediation model showed that facing coping style and fear of disease progression had a chained mediation effect of 0.050 between health literacy and self-management, accounting for 8.36% of the total effect. Conclusions:Self-management in patients with postoperative chemotherapy for colorectal cancer was moderately low. The chain mediating role of coping style and fear of disease progression between health literacy and self-management in postoperative chemotherapy patients with colorectal cancer was established. Nursing staff should strengthen health education for postoperative chemotherapy patients with colorectal cancer, guide patients to face the disease positively, reduce fear, and promote patient self-management.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective To investigate the influencing factors of Mismatch ratio in computed tomography perfusion(CTP)and dif-fusion weighted imaging(DWI)to assess the lesion outcome after treatment in patients with acute ischemic stroke(AIS).Methods Whether there were any differences in clinical and imaging data of AIS patients were analyzed retrospectively between the Mismatch ratio＞1.2 group and the Mismatch ratio≤1.2 group,and between the hemorrhagic transformation group and the non-hemorrhagic transformation group.Results The age of onset and National Institutes of Health Stroke Scale(NIHSS)score of AIS patients in the group with Mismatch ratio＞1.2 were greater than those in the group with Mismatch ratio≤1.2.The Mismatch ratio＞1.2 group had lower incidence of hyperlipidemia,new infarct foci,and higher hypercoagulability,cerebral hemorrhage,as well as large cerebral infarction.The NIHSS score was higher in the hemorrhagic transformation group than the non-hemorrhagic transformation group,and the incidence of large cerebral infarction and digital subtraction angiography(DSA)thrombectomy was higher in the former than in the latter.Multifactorial logistic analysis showed that age,NIHSS score,and hyperlipidemia were independent risk factors for AIS patients with Mismatch ratio＞1.2 and large cerebral infarction was an independent risk factor for hemorrhagic transformation.Conclusion The Mismatch ratio in CTP is correlated with age,NIHSS score,and hyperlipidemia in patients with AIS and large cerebral infarction is correlated with hemorrhagic transformation.

Background and purpose:The incidence of autonomic dysfunction(AD)in patients with advanced cancer is approximately 65%-80%.The neurasthenic symptoms such as dizziness,palpitations and fatigue caused by AD are difficult to alleviate even with sufficient rest,seriously affecting the patients'quality of life.Meanwhile,the cardiovascular autonomic nervous system plays a significant regulatory role in heart rate,myocardial function and myocardial blood flow.AD increases the morbidity and mortality risk of cardiovascular diseases in patients.AD is not only a functional state but might also be an early sign of overall myocardial lesion.Research indicates that after adjusting for age,gender and cardiovascular risk factors,previous radiation exposure is associated with AD manifestations such as increased resting heart rate and abnormal heart rate recovery after exercise.However,there are currently few relevant studies on the effect of radiotherapy on cardiac autonomic function,and the specific injury effects and dose threshold of injury occurrence remain unclear.This study aimed to explore the impact of thoracic radiotherapy on the cardiac autonomic function of patients with malignant tumors by comparing the differences in heart rate variability(HRV)analysis parameters before and after radiotherapy,and to explore the dosimetric risk factors for the occurrence of AD by comparing the dosimetry between the case group and the control group,providing a theoretical basis for optimizing the dose distribution of radiotherapy regimens in order to improve patient prognosis and reduce the occurrence of complications.Methods:We prospectively collected data of patients with malignant tumors who underwent thoracic radiotherapy in the Radiotherapy Department of the Affiliated Hospital of North China University of Science and Technology from February 2023 to December 2023.Inclusion criteria:① Patients who were pathologically confirmed to have malignant tumors(lung cancer breast cancer or esophageal cancer);② patients with radiation therapy indications as recommended by the guidelines;③ patients with an ECOG score of 0-1;④ patients with no significant abnormalities in electrocardiogram and echocardiography results.Exclusion criteria:① previously received chest radiotherapy;② patients with obvious palpitation,chest tightness and chest pain before treatment;③ diabetes,heart disease and other serious underlying diseases;④ anti-arrhythmic drugs are currently being used;⑤ patients who cannot tolerate radiotherapy and who were lost or lost during follow-up.HRV analysis was used to evaluate changes in autonomic nerve function after radiotherapy.Patients with AD were included in the case group,and the remaining patients were included in the control group.Univariate and multivariate logistic regression analysis methods were used to explore the dosimetric risk factors and cardiac dose limitations for the occurrence of AD after thoracic radiotherapy.This study was approved by the ethics committee of Affiliated Hospital of North China University of Science and Technology(ethics number:20230228020).Results:A total of 89 patients with thoracic tumors meeting the study criteria were enrolled in the study.Among them,41(46%)patients experienced cardiac AD after radiotherapy.The cardiac Dmax(6 273.500 cGy vs 4 675.900 cGy,P＜0.001),cardiac Dmean(1513.700 cGy vs 452.050 cGy,P＜0.001),cardiac V5(49.000%vs 21.250%,P＜0.001),V20(30.500%vs 7.300%,P＜0.001),V30(18.700%vs 3.600%,P＜0.001)and V40(10.900%vs 1.500%,P＜0.001)were significantly higher in the case group than in the control group.The results of multivariate logistic regression analysis showed that cardiac V30 was an independent risk factor for the occurrence of cardiac AD[OR(95%CI)=1.583(1.093-2.291),P=0.015].Cardiac V30 could predict the occurrence of radiation-induced cardiac injury with an area under the curve of 0.788,and 17.1%was the optimal cut-offvalue of cardiac V30 for predicting the occurrence of cardiac AD.Conclusion:After thoracic radiotherapy,the cardiac irradiation dose-volume was significantly higher in patients with cardiac AD than in the control group.When cardiac V30 was higher than 17.1%,the risk of cardiac AD in patients significantly increased.

Objective To investigate the molecular mechanism of polysaccharides from Atractylodes macrocephala koidz.(PAM)to treat severe pneumonia.Methods Sixty male SD rats were randomly divided into control group,model group(inoculation of Klebsiella pneumonia by tracheal puncture),positive control group(levofloxacin,18 mg/kg),PAM low-dose group(50 mg/kg)and PAM high-dose group(200 mg/kg)with 12 in each.After oc-currence of severe pneumonia,the rats were orally administered the medicine once daily for 7 day.The lung tissue underwent histopathological examination using HE staining microscopy to find the pathological alterations and evaluate the extent of injury.Wet/dry ratio of lung tissue was measured by weighing method.The leukocytes and neutrophils counts in peripheral blood were determined by hematology analyzer.The level of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in serum and bronchoalveolar lavage fluid(BALF)was detected by enzyme-linked immunosorbent assay.The expression of proteins related to the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway in lung tissues was detected using Western blot analysis.Results Compared with the control group,lung injury score and wet/dry ratio,the number of leukocytes and neutrophils in peripheral blood,the level of TNF-α,IL-1β and IL-6 in serum and in BALF,protein expression of TLR4 and MyD88 and the phosphorylation level of NF-κB p56 in lung tissues from model group were all signifi-cantly increased(P＜0.05).The lung injury of rats in each levofloxacin treatment group exhibited significant im-provement compared to the model group.Among them,the number of leukocytes and neutrophils in peripheral blood of rats in PAM high-dose group decreased significantly(P＜0.05);The level of TNF-α,IL-1β and IL-6 in serum and BALF,the protein expression of TLR4 and MyD88 and the phosphorylation level of NF-κB p56 in lung tissue were significantly decreased(P＜0.05).Conclusions The administration of PAM exerts a specific protective effect against Klebsiella pneumoniae-induced pneumonia in rats,potentially suppress inflammatory response through modu-lation of the TLR4/MyD88/NF-κB signaling pathway.