1.Construction and application of the "Huaxi Hongyi" large medical model
Rui SHI ; Bing ZHENG ; Xun YAO ; Hao YANG ; Xuchen YANG ; Siyuan ZHANG ; Zhenwu WANG ; Dongfeng LIU ; Jing DONG ; Jiaxi XIE ; Hu MA ; Zhiyang HE ; Cheng JIANG ; Feng QIAO ; Fengming LUO ; Jin HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):587-593
Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.
2.Association between blood pressure response index and short-term prognosis of sepsis-associated acute kidney injury in adults.
Jinfeng YANG ; Jia YUAN ; Chuan XIAO ; Xijing ZHANG ; Jiaoyangzi LIU ; Qimin CHEN ; Fengming WANG ; Peijing ZHANG ; Fei LIU ; Feng SHEN
Chinese Critical Care Medicine 2025;37(9):835-842
OBJECTIVE:
To assess the relationship between blood pressure reactivity index (BPRI) and in-hospital mortality risk in patients with sepsis-associated acute kidney injury (SA-AKI).
METHODS:
A retrospective cohort study was conducted to collect data from patients admitted to the intensive care unit (ICU) and clinically diagnosed with SA-AKI between 2008 and 2019 in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database in the United States. The collected data included demographic characteristics, comorbidities, vital signs, laboratory parameters, sequential organ failure assessment (SOFA) and simplified acute physiology scoreII(SAPSII) within 48 hours of SA-AKI diagnosis, stages of AKI, treatment regimens, mean BPRI during the first and second 24 hours (BPRI_0_24, BPRI_24_48), and outcome measures including primary outcome (in-hospital mortality) and secondary outcomes (ICU length of stay and total hospital length of stay). Variables with statistical significance in univariate analysis were included in LASSO regression analysis for variable selection, and the selected variables were subsequently incorporated into multivariate Logistic regression analysis to identify independent predictors associated with in-hospital mortality in SA-AKI patients. Restricted cubic spline (RCS) analysis was employed to examine whether there was a linear relationship between BPRI within 48 hours and in-hospital mortality in SA-AKI patients. Basic prediction models were constructed based on the independent predictors identified through multivariate Logistic regression analysis, and receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of each basic prediction model before and after incorporating BPRI.
RESULTS:
A total of 3 517 SA-AKI patients admitted to the ICU were included, of whom 826 died during hospitalization and 2 691 survived. The BPRI values within 48 hours of SA-AKI diagnosis were significantly lower in the death group compared with the survival group [BPRI_0_24: 4.53 (1.81, 8.11) vs. 17.39 (5.16, 52.43); BPRI_24_48: 4.76 (2.42, 12.44) vs. 32.23 (8.85, 85.52), all P < 0.05]. LASSO regression analysis identified 20 variables with non-zero coefficients that were included in the multivariate Logistic regression analysis. The results showed that respiratory rate, temperature, pulse oxygen saturation (SpO2), white blood cell count (WBC), hematocrit (HCT), activated partial thromboplastin time (APTT), lactate, oxygenation index, SOFA score, fluid balance (FB), BPRI_0_24, and BPRI_24_48 were all independent predictors for in-hospital mortality in SA-AKI patients (all P < 0.05). RCS analysis revealed that both BPRI showed "L"-shaped non-linear relationships with the risk of in-hospital mortality in SA-AKI patients. When BPRI_0_24 ≤ 14.47 or BPRI_24_48 ≤ 24.21, the risk of in-hospital mortality in SA-AKI increased as BPRI values decreased. Three basic prediction models were constructed based on the identified independent predictors: Model 1 (physiological indicator model) included respiratory rate, temperature, SpO2, and oxygenation index; Model 2 (laboratory indicator model) included WBC, HCT, APTT, and lactate; Model 3 (scoring indicator model) included SOFA score and FB. ROC curve analysis showed that the predictive performance of the basic models ranked from high to low as follows: Model 3, Model 2, and Model 1, with area under the curve (AUC) values of 0.755, 0.661, and 0.655, respectively. The incorporation of BPRI indicators resulted in significant improvement in the discriminative ability of each model (all P < 0.05), with AUC values increasing to 0.832 for Model 3+BPRI, 0.805 for Model 2+BPRI, and 0.808 for Model 1+BPRI.
CONCLUSIONS
BPRI is an independent predictor factor for in-hospital mortality in SA-AKI patients. Incorporating BPRI into the prediction model for in-hospital mortality risk in SA-AKI can significantly improve its predictive capability.
Humans
;
Acute Kidney Injury/mortality*
;
Sepsis/complications*
;
Retrospective Studies
;
Hospital Mortality
;
Prognosis
;
Blood Pressure
;
Intensive Care Units
;
Male
;
Female
;
Length of Stay
;
Middle Aged
;
Aged
;
Adult
;
Logistic Models
3.Mingshi Formula (明视方) for Low Myopia in Children with Heart Yang Insufficiency Syndrome: A Multicentre, Double-Blind, Randomised Placebo-Controlled Study
Jianquan WANG ; Xinyue HOU ; Zefeng KANG ; Yingxin YANG ; Xinquan LIU ; Zhihua SHEN ; Xiaoyi YU ; Jing YAO ; Fengming LIANG ; Fengmei ZHANG ; Jingsheng YU ; Ningli WANG ; Man SONG ; Hongrui SUN ; Xin YAN
Journal of Traditional Chinese Medicine 2024;65(6):587-593
ObjectiveTo observe the effectiveness and safety of the Chinese herbal medicine Mingshi Granules (明视方颗粒) for low myopia in children with heart yang insufficiency. MethodsA multicentre, prospective, double-blind randomised controlled study was conducted, in which 290 children with low myopia from 8 centres were randomly divided into 145 cases in the treatment group and 145 cases in the control group, and the treatment group was given education, dispensing glasses, and Chinese herbal medicine Mingshi Granules, while the control group was given education, dispensing glasses, and granules placebo. Both Mingshi Granules and placebo granules were taken orally, 1 bag each time, twice daily, 4 weeks of oral intake and 2 weeks of rest as 1 course of treatment, a total of 4 courses of treatment (24 weeks). Equivalent spherical lenses, best naked-eye distance visual acuity, ocular axis, corneal curvature K1, adjustment amplitude, traditional Chinese medicine (TCM) symptom scores, calculate the amount of progression of equivalent spherical lenses, were observed at the 12th and the 24th week of treatment, at the 36th week and 48th week of follow-up, resectively, the control rate of myopia progression was evaluated at the 24th week, and safety indexes were observed before treatment. ResultsThe amount of progression of equivalent spherical lenses was lower in the treatment group than in the control group at the 48-week follow-up (P<0.05). The control rate of myopia progression at 24 weeks after treatment in the treatment group was higher (57.60%, 72/125) than that in the control group (44.63%, 54/121) (P<0.05). The best naked-eye distance visual acuity at 36-week follow-up in the treatment group was higher than that in the control group (P<0.05). Equivalent spherical lenses were significantly lower in both groups at all observation time points compared with pre-treatment (P<0.05), and were higher in the treatment group than in the control group at the 48-week follow-up (P<0.05). The ocular axes of both groups were significantly higher at each observation time point after treatment and at follow-up compared with before treatment (P<0.05). The amount of eye axis growth in the treatment group was lower than that in the control group at 24 weeks after treatment and at the 48-week follow-up (P<0.05). Corneal curvature K1 was significantly lower in the treatment group at the 24th week of treatment compared to pre-treatment (P<0.05). The magnitude of adjustment in the treatment group was significantly higher at the 36-week follow-up and at the 48-week follow-up than before treatment (P<0.05). The scores of white/dark complexion, white coating thin pulse, fatigue and total TCM symptom scores of children in both groups at the 12th, 24th, 36th and 48th weeks of follow-up were significantly lower than those before treatment (P<0.05); the scores of blurred vision at the 24th and 36th weeks of follow-up were significantly lower than those before treatment (P<0.05); and the scores of blurred vision in the treatment group at the 48th week of follow-up were signi-ficantly lower than those before treatment (P<0.05). In the treatment group, the score of fatigue was higher than that of the control group at the 36-week follow-up, and the score of blurred vision was lower than that of the control group at the 48-week follow-up (P<0.05). No adverse reactions or obvious abnormalities of the safety indexes were observed of the two groups during the treatment. ConclusionChinese herbal medicine Mingshi Granules showed the effect of controlling the progression of low myopia, improving the best naked eye distance visual acuity, slowing down the growth of the eye axis, improving some of the TCM symptoms, with good safety.
4.Effect of home exercise on pain, function and quality of life after operation for rotator cuff injury
Ting YANG ; Jingjie ZHOU ; Tao WANG ; Weiwei ZHU ; Fengming CHU ; Wei CHEN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(12):1461-1472
ObjectiveTo explore the effect of home exercise on pain, function and quality of life after operation for rotator cuff injury. MethodsFrom June, 2023 to June, 2024, 45 patients after operation for rotator cuff injury were selected from Xuzhou Rehabilitation Hospital Affiliated to Xuzhou Medical University and Xuzhou Central Hospital, and randomly divided into conventional group (n = 15), home-based group (n = 15) and combined group (n = 15). The conventional group received an eight-week routine rehabilitation program in hospital, the home-based group received an eight-week home exercise prescription training, and the combined group first received four weeks of routine rehabilitation in hospital, and followed by four weeks of home exercise prescription training. They were assessed with Visual Analogue Scale for pain (VAS), University of California at Los Angeles shoulder rating scale (UCLA), Constant-Murley Score (CMS), range of motion (ROM) of shoulder, and the Short-form of Health Survey-36 (SF-36) before treatment, and four and eight weeks after treatment. ResultsVAS scores decreased in all the three groups four and eight weeks after treatment (Z > 2.964, P < 0.001), which was the most in the home-based group four weeks after treatment (|Z| > 2.531, P < 0.05). The main effect of time was significant in scores of UCLA, CMS, and physical health and mental health of SF-36 (F > 498.102, P < 0.001), which improved after treatment (P < 0.001). The main effect of group was significant in score of mental health of SF-36 (F = 7.408, P = 0.002), which was the most in the home-based group four and eight weeks after treatment (P < 0.01). The interaction was significant in score of physical health of SF-36 (F = 10.138, P < 0.001), which was the least in the home-based group four weeks after treatment (P < 0.05). The main effect of time was significant in every direction of ROM, which improved after treatment (P < 0.001). The interaction was significant in ROM of abduction and external rotation (F > 4.059, P < 0.01), and almost significant in ROM of flexion (F = 2.412, P = 0.055). However, ROM of flexion was less in the home-based group than in the combined group four weeks after treatment (P = 0.047), which was less in the home-based group than in the conventional group eight weeks after treatment (P = 0.042); ROM of abduction was the least in the home-based group four weeks after treatment (P < 0.01), which was less in the home-based group than in the combined group eight weeks after treatment (P = 0.046); ROM of external rotation was less in the home-based group than in the combined group four weeks after treatment (P = 0.022). ConclusionHome exercise is effective on pain, function and quality of life in patients after operation for rotator cuff injury. There are benefits with both home exercise and institution-based rehabilitation, and almost the same in a whole eight weeks after treatment.
5.The Predictive Value of MMP-9 the and NLR Values for Bleeding Transformation after the Revascularization in Acute Ischemic Stroke
Baogang HUANG ; Kang DU ; Fengming XU ; Haohao WU ; Shaoyong GUAN ; Qianjun FAN ; Junsu YANG ; Fang QIAN
Journal of Kunming Medical University 2024;45(1):116-121
Objective To study the correlation between the changes of matrix metalloproteinase-9(MMP-9)and neutrophil/lymphocyte ratio(NLR)before and after the revascularization of acute ischemic stroke(AIS),so as to find biomarkers to predict the bleeding transformation risk of AIS patients.Methods From February 2022 to December 2022,161 patients admitted to the Stroke Center of Qujing Hospital Affiliated to Kunming Medical University with AIS werre divided in to the hemorrhagic transformation group and the non-hemorrhagic transfor-mation groupand treated with revascularization(intravenous thrombolysis,endovascular treatment,combined the intravenous thrombolysis with endovascular treatment).Among them,there were 46 cases in the hemorrhagic transformation group and 115 cases in the non hemorrhagic transformation group.And the general data,NLR value and MMP-9 before and after the revascularization were compared between the two groups.Results There was no statistical difference in general data between the two groups(all P>0.05)except for C-reactive protein in hemorrhagic transformation group and in non-hemorrhagic transformation group(P<0.001).The white blood cells,neutrophils,neutrophil percentage,neutrophil absolute value,lymphocyte absolute value,NLR and MMP-9 value in hemorrhagic transformation group were significantly higher than those in non-hemorrhagic transformation group before the treatment and there was a statistical significance(P<0.05).After revascularization,the indexes of blood routine and MMP-9 were significantly higher than those before the revascularization,and the increase in hemorrhagic transformation group was more obvious than that in non-hemorrhagic transformation group and there was a statistical significance(P<0.001),The ROC curve showed that the area under the curve(AUC)of NLR and MMP-9 predicting bleeding transformation after AIS revascularization were 0.74 and 0.90.Conclusion NLR,MMP-9 are associated with the risk of bleeding transformation in AIS patients after the revascularization and can they can be used as the predictive factors for bleeding transformation risk.
6.Predictive value of systemic immune-inflammatory index for complicating venous thrombo embolism in patients with lung cancer
Jing FENG ; Fengming LUO ; Ying YANG ; Juan HAN ; Xiaobo HU
Chongqing Medicine 2024;53(15):2308-2312,2318
Objective To investigate the predictive value of systemic immune-inflammation index (SII) for venous thrombo embolism (VTE) in patients with lung cancer.Methods The patients with lung cancer admitted and treated in Chengdu Municipal Second People's Hospital from March 2022 to October 2023 were selected as the study subjects and divided into the VTE group (n=33) and the non-VTE group (n=37) ac-cording to whether or not complicating VTE.The clinical characteristics and laboratory indexes were collect-ed.The multivariate logistic regress was used to analyze the influencing factors.The receiver operating charac-teristic (ROC) curve was drawn.The difference of the areas under curve (AUC) was compared.The Kaplan-Meier survival curve was used to evaluate the risk stratification capability of the related variables for VTE oc-currence in the patients with lung cancer.Results There were statistically significant differences in WBC,neutrophil,lymphocyte,albumin (ALB),D-dimer (D-D),plasma viscosity,neutrophil-to-lymphocyte ratio (NLR),platelet-to-lymphocyte ratio (PLR) and SII between the two groups (P<0.05).The multivariate lo-gistic regression analysis showed that high SII,tumor stage (Ⅲ-Ⅳ stage) and plasma viscosity were inde-pendent risk factors for VTE occurrence in the patients with lung cancer (P<0.05).The ROC curve analysis showed that AUC of the Khorana score,SII,modified Khorana score,NLR and PLR were 0.747,0.776,0.866,0.754 and 0.672,respectively.The predictive efficiency of SII for VTE occurrence in the patients with lung cancer was better than that of Khorana score,NLR and PLR.Conclusion High SII is an independent risk factor for VTE occurrence in the patients with lung cancer,its risk stratification for VTE occurrence in the pa-tients with lung cancer is conducive to early recognize the high risk population.
7.Tongxie Yaofang Regulates Expression of NKG2DL to Enhance Anti-tumor Effect of NK Cells in Colon Cancer under Chronic Stress
Yan'e HU ; Yuqing HUANG ; Yi YANG ; Yifang JIANG ; Xi FU ; Fengming YOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):103-111
ObjectiveTo observe the effect of Tongxie Yaofang on the function of tumor-related natural killer (NK) cells under chronic stress and explore the possible molecular mechanism. MethodFifty SPF-grade BABL/C male mice were randomized into normal, model, and low-, medium-, and high-dose (6.825, 13.65, and 27.3 g·kg-1, respectively) Tongxie Yaofang groups, with 10 mice in each group. Other groups except the blank group were subjected to 7 days of chronic restraint stress, and then forced swimming and tail suspension tests were carried out to evaluate the modeling performance. After the successful modeling, rats in Tongxie Yaofang groups were administrated with low-, medium-, and high-doses of Tongxie Yaofang by gavage, while those in the other groups were administrated with normal saline by gavage. After 14 days, each group of mice was inoculated with subcutaneous colon cancer to establish the model of colon cancer under chronic stress. The pathological changes of the tumor tissue in each group of mice were observed using hematoxylin-eosin (HE) staining. The content of CD49b-positive cells in the peripheral blood and tumor tissue of mice was measured by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the content of molecules associated with NK cell activation in the peripheral blood. Western blot was employed to determine the protein levels of major histocompatibility complex class Ⅰ polypeptide-related sequences A and B (MICA+MICB) and UL-16-binding protein 1 (ULBP1) in the tumor tissue. ResultCompared with the normal group, the model group showed a decrease in 5-hydroxytryptamine (5-HT) content and an increase in corticosterone (CORT) content in the serum (P<0.05). Compared with the model group, Tongxie Yaofang increased the 5-HT content and decreased the CORT content (P<0.05, P<0.01). Compared with the normal group, the modeling increased the tumor volume and weight (P<0.05), while Tongxie Yaofang inhibited such increases with no statistical significance. The tumor cells in the model group presented neat arrangement, irregular shape, uneven size, obvious atypia, common nuclear division, and small necrotic area, and blood vessels were abundant surrounding the tumor cells. Compared with the model group, Tongxie Yaofang groups showed sparse arrangement of tumor cells, different degrees of patchy necrosis areas in the tumor, and karyorrhexis, dissolution, and nuclear debris in the necrotic part. Compared with the normal group, the model group showed reduced CD49b-positive cells in the peripheral blood and tumor tissue (P<0.01). Compared with the model group, Tongxie Yaofang increased CD49b-positive cells (medium dose P<0.01, high dose P<0.05, P<0.01). Compared with the normal group, the modeling lowered the serum levels of granzymes-B (Gzms-B), perforin (PF), interferon (IFN)-γ, and tumor necrosis factor (TNF)-α (P<0.05, P<0.01). Compared with the model group, low-dose Tongxie Yaofang elevated the serum levels of PF, Gzms-B, and TNF-α (P<0.05, P<0.01), and medium-dose Tongxie Yaofang elevated the serum levels of Gzms-B, PF, IFN-γ, and TNF-α (P<0.05, P<0.01). In addition, high-dose Tongxie Yaofang elevated the serum levels of PF, IFN-γ, and TNF-α (P<0.01). Compared with the normal group, the model group presented down-regulated protein level of ULBP1 (P<0.05). Compared with the model group, low-, medium-, and high-dose Tongxie Yaofang up-regulated the protein level of ULBP1 (P<0.05, P<0.01), and medium- and high-dose Tongxie Yaofang up-regulated the protein level of MICA+MICB (P<0.05, P<0.01). ConclusionTongxie Yaofang may promote NK cell activation by up-regulating the expression of MICA+MICB and ULBP1, thereby delaying the progression of colon cancer under chronic stress.
8.Intervention Effect and Mechanism of Tongxie Yaofang-Containing Serum on Cell Cycle and Apoptosis of Colon Cancer HCT116 Cells
Yifang JIANG ; Yan'E HU ; Yi YANG ; Xi FU ; Jie ZHU ; Fengming YOU
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(10):3221-3229
Objective To observe the effect of Tongxie Yaofang-containing serum on the cell cycle and apoptosis of colon cancer HCT116 cells,and to explore its possible biological mechanism.Methods Colon cancer HCT116 cells were divided into blank group and Tongxie Yaofang-containing serum group with different concentrations.Cell proliferation and activity detection-8(CCK8)was used to detect the effect of each group on the viability of HCT116 cells at 24,48 and 72 h;Flow cytometry was used to detect the apoptosis and cycle arrest of HCT116 cells induced by different concentrations of Tongxie Yaofang-containing serum;Western blot was used to detect the protein expression level of Cell Cycle Regulatory Protein P21(P21),Cyclin B1,cyclin-dependent protein kinases-1(CDK1),B-lymphoma-2(Bcl-2),Bcl-2-related X protein(Bax),phosphatidylinositol-3-kinase(PI3K),phosphorylated phosphatidylinositol-3-kinase(p-PI3K),protein kinase B(Akt)and phosphorylated protein kinase B(p-Akt)after different concentrations of Tongxie Yaofang-containing serum intervention.Results CCK8 showed that compared with the 10%blank group,10%Tongxie Yaofang-containing serum had a significant inhibitory effect on the viability of HCT116 cells only at 48 h(P<0.01);Compared with the 20%blank group,20%Tongxie Yaofang-containing serum could inhibit the viability of HCT116 cells at 48 and 72 h(P<0.01,P<0.05),and the increase of blank serum will not inhibit the viability of HCT116 cell,so 10%blank serum and 48 h were selected as the drug control and intervention time in the subsequent experiment.Flow Cytometry showed that,compared with the blank group,10%and 20%Tongxie Yaofang-containing serum could arrest HCT116 cell cycle in G2/M phase after 48 h of intervention(P<0.01),and induce HCT116 cell apoptosis.At the same time,Western blot showed that Tongxie Yaofang-containing serum could increase the expression of P21 and Bax to varying degrees,and reduces Cyclin B1,CDK1,Bcl-2,p-PI3K,p-Akt expression(P<0.05,P<0.01).Conclusion Tongxie Yaofang can inhibit the proliferation and induce apoptosis of colon cancer HCT116 cells,and its mechanism may be related to the inhibition of PI3K/Akt signaling pathway.
9.Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA.
Wenxin ZHANG ; Xiaohui PAN ; Yanjun XU ; Hongjie GUO ; Mingming ZHENG ; Xi CHEN ; Honghai WU ; Fengming LUAN ; Qiaojun HE ; Ling DING ; Bo YANG
Acta Pharmaceutica Sinica B 2023;13(6):2585-2600
Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.
10.Tongxie Yaofang Regulates T Lymphocyte Subsets to Improve Immune Microenvironment of Colorectal Cancer Under Chronic Stress
Yi YANG ; Yane HU ; Yifang JIANG ; Ningning CHEN ; Ran YAN ; Jie ZHU ; Fengming YOU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(12):46-54
ObjectiveTo explore the effect of Tongxie Yaofang on the immune microenvironment of colorectal cancer in mice under chronic stress and the underlying mechanism. MethodA total of 40 male SPF BABL/C mice were randomized into normal group, stress group, Tongxie Yaofang group (13.65 g·kg-1), and Tongxie Yaofang-stress group (13.65 g·kg-1), with 10 in each group. Chronic restraint stress was induced in mice and administration (ig) of Tongxie Yaofang began after 7 days of stress. On the 14th day, forced swim and tail suspension tests were used to examine the behavioral changes of mice after stress and the subcutaneous colorectal tumor was implanted in each group of mice. The effect of this prescription on the body mass and tumor volume of mice was observed. After the last administration, mouse serum and tumor samples were collected. The content of T lymphocytes (CD3+, CD4+, CD8+, and CD4+/CD8+) in tumor was detected by immunohistochemistry and flow cytometry and levels of corticosterone (CORT) in peripheral blood, and interleukin (IL)-2, interferon-γ (IFN-γ), IL-6, and IL-10 in the serum were determined by enzyme-linked immunosorbent assay (ELISA). The protein expression of inhibitor of nuclear factor-κB(IκB) kinase α/β (IKKα/β), nuclear factor-κB (NF-κB)α (IκBα), NF-κB p65, and phosphorylated (p)-NF-κB p65 was measured by Western blot. ResultCompared with the normal group, the stress group had large tumor volume (P<0.05), low content of CD3+, CD4+, and CD4+/CD8+ (P<0.05, P<0.01), high content of CD8+, low content of T helper 1 (Th1)-secreted IFN-γ (P<0.05), high content of T helper 2 (Th2)-secreted IL-10 (P<0.05) and CORT (P<0.05), high protein expression of p-NF-κB p65, NF-κB p65, and IKKα/β (P<0.05), and low protein expression of IκBα (P<0.05). Compared with the normal group, the Tongxie Yaofang group showed slow tumor growth, high content of CD3+, CD4+, and CD4+/CD8+ (P<0.01), low content of CD8+ (P<0.05), high content of Th1-secreted IL-2 and IFN-γ (P<0.05), low content of Th2-secreted IL-6 and IL-10 (P<0.05), low content of CORT, low protein expression of p-NF-κB p65, NF-κB p65, and IKKα/β (P<0.05), and high protein expression of IκBα (P<0.01). Tongxie Yaofang-stress group demonstrated slower tumor growth, higher content of CD3+, CD4+, and CD4+/CD8+ (P<0.01), smaller content of CD8+ (P<0.05), higher content of IL-2 and IFN-γ (P<0.05), lower content of IL-6, IL-10 (P<0.05), and CORT (P<0.05), lower protein expression of p-NF-κB p65, NF-κB p65, and IKKα/β (P<0.05,P<0.01), and higher protein expression of IκBα (P<0.01) than the stress group. ConclusionTongxie Yaofang can delay the growth of colorectal cancer under chronic stress and alleviate the deterioration of the immune microenvironment, possibly by inhibiting NF-κB signaling pathway, regulating the function of T lymphocyte subsets, and thus suppressing the secretion of pro-inflammatory factors.

Result Analysis
Print
Save
E-mail