This paper compares the philosophical structures of doctrine of five evolutive phases and six climate factors and The Book of Changes （《周易》） from three dimensions of "time， position， and virtue"， aiming to reveal the penetration of The Book of Changes thought in the formation of the doctrine of five evolutive phases and six climate factors and its own theoretical transformation. Both the "doctrine" and the "book" centered on "time"， recognizing temporal order through observation of celestial phenomena and calendar formulation. The Book of Changes emphasizes "seizing the timely moment" to master the principles of change in all things， while doctrine of five evolutive phases and six climate factors focuses on "understanding time" to clarify how qi relates to temporal phases. Regarding position， both treat it as time-derived and philosophically significant within a six-tier structure. The The Book of Changes uses yao （爻） positions for judging auspiciousness， inauspiciousness， regret and distress， with such judgement permeating the overall structure of the hexagram； the doctrine of five evolutive phases and six climate factors uses qi positions， where "dangwei （当位）" denotes normative qi transformation governing the overall pattern. Both hold that "virtue" arises from time‑position harmony， representing conformity to time and suitability to position. In The Book of Changes， "virtue" serves to encapsulate the attributes of things and the principles of heaven and earth， whereas the doctrine of five evolutive phases and six climate factors furhter extends "virtue" to denote the normative state of qi transformation. Thus， the intellectural structure of time， position and virtue in the doctrine of five evolutive phases and six climate factors was influenced by Yijing scholarship， within which it completed its theoretical evolution distinctly.

[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Objective To compare the dosimetric differences, plan complexity, verification pass rate, and execution efficiency of volumetric modulated arc therapy (VMAT) plans designed for post-mastectomy radiotherapy of breast cancer using Halcyon 2.0 and VitalBeam accelerators in flattening filter-free mode. Methods A retrospective analysis was conducted on imaging data from 87 female breast cancer patients aged 29 to 75 (49.9 ± 9.9) years who underwent modified radical mastectomy followed by radiotherapy. VMAT plans were designed using both VitalBeam and Halcyon accelerators in flattening filter-free mode. The dosimetric parameters, plan complexity, verification pass rate, and execution efficiency were compared between the plans designed for both accelerators, with a significance level of P<0.05. Results In terms of target volume parameters, Halcyon 2.0 plans demonstrated superior homogeneity index and conformity index. For organs at risk, the Halcyon 2.0 plans showed lower doses for the lungs (D_20% and D_mean) and heart (D_mean) compared to the VitalBeam plans (all P<0.05). Regarding plan complexity, Halcyon 2.0 plans exhibited better median average aperture area variation (0.35 ± 0.02), smaller aperture score, and larger median plan aperture area than VitalBeam plans (all P<0.05). However, VitalBeam plans had a superior median modulation complexity score (0.28 ± 0.01) compared to Halcyon 2.0 plans (P<0.05). Patient plans were assessed using the ArcCHECK phantom, revealing higher pass rates and significantly shorter execution time for Halcyon plans compared to VitalBeam plans (P<0.05). Conclusion Both Halcyon 2.0 and VitalBeam accelerators can provide high-quality VMAT plans for postoperative radiotherapy of breast cancer, with excellent verification pass rates ensuring treatment accuracy and efficacy. However, Halcyon 2.0 offers lower plan complexity, simplifies the treatment planning process, and reduces execution time, thereby achieving higher treatment efficiency and demonstrating greater advantages in clinical applications.

AIM To investigate the inhibitory effect of gallic acid on HCC1806 triple-negative breast cancer xenograft growth in nude mice.METHODS The nude mouse models of HCC1806 triple-negative breast cancer xenograft growth were established and randomly divided into the model group,the gallic acid group(200 mg/kg)and the adriamycin group(5 mg/kg),with 6 mice in each group.After 21 days of respective drug administration,the nude mice were killed and had their xenografts procured and measured.The nude mice had their serum levels of IL-6 and TNF-α detected by ELISA;their morphological changes of xenografts observed with HE staining;their protein expressions of p53,PCNA and Ki67 in xenograft detected by immunohistochemistry;their mRNA expressions of PCNA,Ki67,Bcl-2,Bax,Caspase-3,PI3K,Akt,JNK and p38 detected by RT-qPCR;and their protein expressions of Bcl-2,Bax,Caspase-3,cleaved-Caspase-3,PI3K,p-PI3K,Akt,p-Akt,JNK,p-JNK,p38 MAPK and p-p38 MAPK in xenografts detected by Western blot.RESULTS Compared with the model group,the groups intervened with either gallic acid or adriamycin shared decreased tumor weight(P＜0.05);increased serum levels of IL-6 and TNF-α(P＜0.05,P＜0.01);condensed or irregular nuclei of xenograft,and increased number of cell necrosis;increased protein expressions of p53 and Bax and the ratios of cleaved-Caspase-3/Caspase-3,p-JNK/JNK and p-p38/p38 in xenograft(P＜0.01);decreased protein expressions of PCNA,Ki67 and Bcl-2 and the ratios of p-PI3K/PI3K and p-Akt/Akt(P＜0.01);decreased mRNA expressions of PCNA,Ki67,Bcl-2,PI3K and Akt(P＜0.05,P＜0.01);and increased mRNA expressions of Caspase-3,Bax,JNK and p38(P＜0.05,P＜0.01).CONCLUSION Gallic acid can inhibit HCC1806 triple-negative breast cancer xenograft growth in nude mice,and the underlying mechanism may involve suppression of pro-cell proliferation proteins,activation of pro-apoptotic proteins,and modulation of the PI3K/Akt and JNK/p38 signaling pathways.

Objective:To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with vimentin (VIM) and carbohydrate antigen 19-9 (CA19-9) for hilar cholangiocarcinoma (HCCA).Methods:A retrospective analysis was conducted on the case data of patients with HCCA and inflammatory pseudotumor of the liver admitted to Liaocheng People′s Hospital from June 2019 to June 2022. Among them, 68 patients with HCCA who underwent radical surgical resection were the observation group, and 60 patients with inflammatory pseudotumor of the liver were the control group. All patients underwent CEUS examination before the operation. The results of ultrasound manifestations were analyzed, and the levels of tissue VIM and serum CA19-9 in the two groups were compared. The relationship between tissue VIM, serum CA19-9 levels and the clinicopathological characteristics of patients with HCCA was analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the value of CEUS parameters, tissue VIM and serum CA19-9 levels in the diagnosis of HCCA.Results:Among the 68 patients with HCCA, " fast in and fast out" was presented in CEUS. The numbers of cases with high enhancement, equal enhancement and low enhancement in the arterial phase were 47(69.12%), 16(23.53%) and 5(7.35%), respectively. The numbers of cases with low enhancement and equal enhancement in the portal vein stage were 53 cases (77.94%) and 15 cases (22.06%), respectively. All 68 cases (100%) in the delay period were of low enhancement. The proportions of patients with peripheral annular enhancement, overall heterogeneous enhancement and overall uniform enhancement in 60 cases of liver inflammatory pseudotumor were 20.00%(12/60), 40.00%(24/60) and 40.00%(24/60), respectively. There was no statistically significant difference in the time of initial enhancement between the two groups ( P>0.05). The peak time, isoenhancement time and the time of initial regression in the observation group were all longer than those in the control group (all P<0.05). The positive rate of VIM and the level of serum CA19-9 in the observation group were both higher than those in the control group (all P<0.05). The expression of VIM in the tissues of HCCA patients was related to tumor size, degree of differentiation, vascular invasion, lymph node metastasis and tumor node metastasis (TNM) stage (all P<0.05), but not related to nerve invasion ( P>0.05). The level of serum CA19-9 was related to tumor size, degree of differentiation, vascular invasion, nerve invasion, lymph node metastasis and TNM stage (all P<0.05). The results of the ROC curve showed that the combined detection of each parameter of CEUS (time to peak, time to start fading, time to equal enhancement) with VIM expression and serum CA19-9 level had a higher diagnostic efficacy for HCCA than the individual detection of each index. Conclusions:CEUS parameters, tissue VIM expression and serum CA19-9 all have certain diagnostic values for HCCA, and the combined detection has higher diagnostic efficacy.

Objective:To investigate the effects of lezumab adjuvant therapy on the degree of retinal vasculopathy and immune response in the treatment of macular central diabetic retinopathy (DR).Methods:From July 2022 to December 2023, 120 patients with DR in macular central who received treatment in the Xi′an People′s Hospital (Xi′an Fourth Hospital) were retrospectively selected and divided into two groups according to the treatment methods: the observation group (60 cases, lezumab combined with sitagliptin), and the control group (60 cases, sitagliptin). Patients′glucose metabolism, visual acuity, degree of retinopathy, inflammation [tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-10 (IL-10)] and angiogenesis related factors [serum vascular endothelial growth factor (VEGF), midkine (MK), 5′-nucleotidase (CD73)] were evaluated, and the curative efficacy of the two groups was compared. The security of the two schemes was compared.Results:Compared with the control group, the serum concentrations of MK, CD73, TNF-α and VEGF were lower in the observation group after treatment: (1.44 ± 0.06) ng/L vs. (1.67 ± 0.11) ng/L, (1.10 ± 0.27) ng/L vs. (1.31 ± 0.26) ng/L, (11.62 ± 0.89) ng/L vs. (15.96 ± 4.42) ng/L, (84.07 ± 27.07) ng/L vs. (100.72 ± 16.05) ng/L, while the concentration of IL-10 was higher: (65.65 ± 8.68) ng/L vs. (60.02 ± 5.07) ng/L, with statistically significant differences ( P<0.05). There were no statistically significant differences in fasting blood glucose (FBG) and 2 h postprandial blood glucose between two groups before and after treatment ( P>0.05). After treatment, the macular thickness and visual field gray value in the observation group were lower than those in the control group: (302.81 ± 77.08) μm vs. (336.44 ± 10.35) μm, (1.55 ± 0.43)% vs. (2.09 ± 0.51)% ( P<0.05). After 3 months of treatment, the visual acuity in the observation group was higher than that in the control group: 0.493 ± 0.103 vs. 0.439 ± 0.084 ( P<0.05). No serious adverse reactions occurred in both groups. Conclusions:Lezumab assisted sitagliptin has a significant effect in the treatment of DR, which can reduce the degree of lesions, improve vision, and reduce the levels of inflammation and angiogenesis related factors.

Objective:To investigate teachers' evaluation and willingness and the influencing factors regarding the adoption of the flipped classroom teaching mode in undergraduate pediatrics education.Methods:From December 2022 to December 2024, a questionnaire survey was conducted among the teachers who were responsible for teaching Child Health and Disease（Pediatrics) to the eight-year clinical medicine students at Peking University Health Science Center. Their views, evaluation, and willingness of implementing the flipped classroom teaching mode were investigated. Logistic regression analysis was performed using SPSS 26.0 software to explore the factors influencing teachers' willingness to adopt the flipped classroom teaching mode.Results:A total of 102 questionnaires were collected. Among the teachers, 20.59%（ n=21) believed that the teaching effect of the flipped classroom was better than that of the traditional class, 58.82%（ n=60) considered its effectiveness comparable, and 20.59%（ n=21) found it less effective. The most influential factors affecting the effectiveness of flipped classroom were students' self-learning with online videos [(4.39±0.73) points], student participation in the flipped classrooms [(4.26±0.72) points], the adequacy of teachers' pre-class preparation [(4.18±0.65) points], and the suitability of the teaching content for the flipped classroom [(4.11±0.76) points]. Teachers believed that the flipped classroom significantly enhanced students' autonomous learning ability [(4.11±0.63) points], clinical thinking [(4.04±0.58) points], and expression skills [(3.80±0.61) points]. Additionally, 78.43%（ n=80) of the teachers expressed willingness to continue participating in flipped classroom teaching. Factors influencing teachers' willingness to adopt the flipped classroom included gender, satisfaction with students' classroom participation, and personal experience with the effectiveness of the flipped classroom（ P<0.05). Conclusions:The flipped classroom teaching mode is well-accepted by teachers. Students' classroom participation affects teachers' willingness to continue using the flipped classroom teaching mode. In the future, the content of flipped classroom should be arranged individually according to specific teaching objectives to increase students' classroom participation and promote the cultivation of students' ability.

Objective To explore the application of goal-directed fluid therapy based on pulse pressure variation rate(PPV)combined with low central venous pressure(LCVP)technique in liver surgery.Methods A total of 86 patients who underwent liver lobe/segment resection in our hospital from January 2022 to December 2023 were included,and randomly divided into two groups by random sequence method.Patients in the conventional group were treated with LCVP technique,while patients in the test group were given PPV goal-directed intervention on the basis of the conventional group.The surgical indicators,hemodynamic indicators,cognitive function,adverse reactions and recovery of gastrointestinal function of patients in the two groups were compared.Results There was no statistically significant difference in the operation time,Pringle maneuver time,first postoperative exhausting time or first postoperative defecation time of patients between the two groups(P>0.05).However,the intraoperative blood loss,intraoperative fluid infusion volume and hospital stay of patients in the test group were all less/shorter than those in the conventional group(P<0.05).Compared with the time point of T0,patients in the two groups showed increased heart rate(HR)but decreased mean arterial pressure(MAP)and central venous pressure(CVP)at time points of T1 and T2(P<0.05).There was no statistically significant difference in the HR or MAP of patients between the two groups at time points of T0,T1,T2 and T3(P>0.05).At time points of T1 and T2,the CVP of patients in the test group was lower than that in the conventional group(P<0.05).One day after operation,the mini-mental state examination(MMSE)score of patients in the test group was higher than that in the conventional group(P<0.05).The MMSE scores 7 days after operation of patients in the two groups were higher than those 1 day after operation(P<0.05).Patients in the test group had a lower total incidence of adverse reactions and a shorter recovery time of gastrointestinal function than those in the conventional group(P<0.05).Conclusion The goal-directed fluid therapy based on PPV combined with LCVP technique has a good application effect in liver surgery,which can reduce intraoperative blood loss and fluid infusion volume of patients,shorten hospital stay,increase hemodynamic stability,improve postoperative cognitive dysfunction,and promote the recovery of gastrointestinal function,with a relatively high treatment safety.

Objective To screen the differentially expressed circular RNA(circRNA)in peripheral blood of patients with type 2 diabetic nephropathy(T2DN)and study the correlation between the expression of circAKT3 level and renal fibrosis.Methods A retrospectively study was conducted on 176 T2DM patients admitted to Mianyang 404 Hospital from December 2022 to December 2023 based on whether the patients developed DN,they were divided into a simple T2DM group(n=60)and DN group(n=116).At the same time,30 healthy subjects who underwent physical examination in Mianyang 404 Hospital during the same period were selected as the control group.Clinical data of all subjects were collected.DN patients were divided into microalbuminuria group(M-DN group,n=66)and macroalbuminuria group(MS-DN group,n=50)according to Mogensen classification criteria.Twenty samples were randomly selected from the control group,M-DN group,T2DM group and MS-DN group,and 2 ml peripheral venous blood was extracted for RNA extraction and circRNA microarray scanning analysis to screen the differentially expressed circRNA.The correlation between the most significant differential circRNA expression level and renal fibrosis markers and renal function indicators was statistically analyzed.Receiver operator characteristic(ROC)curve was used to analyze the diagnostic efficacy of circAKT3 for DN.Results Compared with the control group,the level of circAKT3 in MS-DN patients was down-regulated by 9.72 times,which was the most significantly down-regulated circRNA.qRT-PCR showed that compared with the control group,the relative expression of circAKT3 in the T2DM group,M-DN group and MS-DN group was 0.85±0.23,0.54±0.13 and 0.12±0.09,respectively,with the progression of DN,the relative expression level of circAKT3 in peripheral blood of patients gradually decreased,and the differences were statistically significant(t=5.100,8.568,10.960,all P＜0.001).Spearman correlation test showed that the level of circAKT3 in peripheral blood of DN patients was correlated with the duration of diabetes,serum Creatinine,BUN,cystatin C,TGF-β,CIV,PCIII and Alb were negatively,correlated(r=-0.756～-0.621,all P＜0.05).Glomerular filtration rate was positively correlated(r=0.695,P=0.010).ROC curve analysis showed that the sensitivity and specificity of circAKT3 in the diagnosis of DM were 75.3%and 71.1%,respectively,and the AUC was 0.792.The sensitivity,specificity and AUC for M-DN were 90.3%,85.7%and 0.875,respectively,and the sensitivity,specificity and the AUC for MS-DN were 88.2%,87.6%and 0.916,respectively.Conclusion The level of serum circAKT3 is significantly down-regulated in DN patients,which can be used as a potential auxiliary diagnostic marker of DN.