ObjectiveTo investigate the mechanisms of Zuojinwan in the treatment of colorectal cancer from the perspective of inhibiting M2 polarization of tumor-associated macrophages. MethodsA colorectal cancer mouse model was established by azoxymethane （AOM）/dextran sulfate sodium （DSS）. Body weight was recorded， disease activity index （DAI） and tumor number were calculated， and hematoxylin-eosin （HE） staining was used to observe colonic pathological changes. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， transforming growth factor-β （TGF-β）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in colonic homogenates. Immunohistochemistry was used to detect proliferating cell nuclear antigen （PCNA） expression in the colon， and immunofluorescence was used to detect mannose receptor （CD206） expression in macrophages. In vitro， M2 macrophages were induced using IL-4/IL-13， and macrophages were treated with different concentrations of Zuojinwan-containing serum. CD206 and differentiation cluster 86 （CD86） were analyzed by flow cytometry. A CT26 and RAW264.7 macrophage co-culture system was established， and the migration and proliferation abilities of CT26 cells were detected using Transwell assays and trypan blue exclusion. Finally， proteomics was used to screen key proteins and signaling pathways involved in Zuojinwan-mediated inhibition of M2 polarization of tumor-associated macrophages in colorectal cancer， and Western blot was used for validation. ResultsIn animal experiments， compared with the blank group， mice in the model group showed significantly decreased body weight （P<0.05）， significantly increased DAI scores （P<0.01）， and significantly increased tumor number （P<0.01）， with severe colonic carcinogenesis and lymphatic metastasis. The protein expression levels of PCNA and CD206 were significantly increased （P<0.01）， and the levels of IL-6， IL-1β， TNF-α， and TGF-β in colonic homogenates were significantly increased （P<0.01）. Compared with the model group， mice in the Zuojinwan intervention group showed significantly higher body weight （P<0.05）， significantly decreased DAI scores （P<0.01）， and significantly reduced tumor numbers （P<0.01）. The protein levels of PCNA and CD206 were significantly decreased （P<0.05）， and the levels of IL-6， IL-1β， TNF-α， and TGF-β in colonic homogenates were significantly decreased （P<0.05）. In the CT26 and RAW264.7 co-culture system in vitro， compared with the blank group， co-culture with M2-type RAW264.7 macrophages significantly increased CT26 cell migration rate and proliferation number （P<0.01）. Compared with the M2 group （M2-type macrophages）， the proportion of CD86 was significantly increased in the Zuojinwan-containing serum group （P<0.01）， while the CT26 cell migration rate and proliferation number were significantly decreased in the 8% Zuojinwan-containing serum group （P<0.01）. Proteomics analysis indicated that tumor necrosis factor-α-induced protein 8-like protein 1 （TIPE1） may be a key target through which Zuojinwan regulates macrophage phenotypic transformation to inhibit colorectal cancer. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway showed the highest enrichment. Compared with the blank group， the levels of TIPE1， p-PI3K， and p-Akt in M2 macrophages were significantly increased （P<0.05，P<0.01）. After treatment with Zuojinwan-containing serum， the levels of TIPE1， p-PI3K， and p-Akt were significantly decreased （P<0.05，P<0.01）. ConclusionZuojinwan may inhibit colorectal cancer proliferation and migration by suppressing M2 polarization of tumor-associated macrophages， which may be associated with inhibition of the PI3K/Akt signaling pathway in tumor-associated macrophages.

ObjectiveTo investigate the mechanisms of Zuojinwan in the treatment of colorectal cancer from the perspective of inhibiting M2 polarization of tumor-associated macrophages. MethodsA colorectal cancer mouse model was established by azoxymethane （AOM）/dextran sulfate sodium （DSS）. Body weight was recorded， disease activity index （DAI） and tumor number were calculated， and hematoxylin-eosin （HE） staining was used to observe colonic pathological changes. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， transforming growth factor-β （TGF-β）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in colonic homogenates. Immunohistochemistry was used to detect proliferating cell nuclear antigen （PCNA） expression in the colon， and immunofluorescence was used to detect mannose receptor （CD206） expression in macrophages. In vitro， M2 macrophages were induced using IL-4/IL-13， and macrophages were treated with different concentrations of Zuojinwan-containing serum. CD206 and differentiation cluster 86 （CD86） were analyzed by flow cytometry. A CT26 and RAW264.7 macrophage co-culture system was established， and the migration and proliferation abilities of CT26 cells were detected using Transwell assays and trypan blue exclusion. Finally， proteomics was used to screen key proteins and signaling pathways involved in Zuojinwan-mediated inhibition of M2 polarization of tumor-associated macrophages in colorectal cancer， and Western blot was used for validation. ResultsIn animal experiments， compared with the blank group， mice in the model group showed significantly decreased body weight （P<0.05）， significantly increased DAI scores （P<0.01）， and significantly increased tumor number （P<0.01）， with severe colonic carcinogenesis and lymphatic metastasis. The protein expression levels of PCNA and CD206 were significantly increased （P<0.01）， and the levels of IL-6， IL-1β， TNF-α， and TGF-β in colonic homogenates were significantly increased （P<0.01）. Compared with the model group， mice in the Zuojinwan intervention group showed significantly higher body weight （P<0.05）， significantly decreased DAI scores （P<0.01）， and significantly reduced tumor numbers （P<0.01）. The protein levels of PCNA and CD206 were significantly decreased （P<0.05）， and the levels of IL-6， IL-1β， TNF-α， and TGF-β in colonic homogenates were significantly decreased （P<0.05）. In the CT26 and RAW264.7 co-culture system in vitro， compared with the blank group， co-culture with M2-type RAW264.7 macrophages significantly increased CT26 cell migration rate and proliferation number （P<0.01）. Compared with the M2 group （M2-type macrophages）， the proportion of CD86 was significantly increased in the Zuojinwan-containing serum group （P<0.01）， while the CT26 cell migration rate and proliferation number were significantly decreased in the 8% Zuojinwan-containing serum group （P<0.01）. Proteomics analysis indicated that tumor necrosis factor-α-induced protein 8-like protein 1 （TIPE1） may be a key target through which Zuojinwan regulates macrophage phenotypic transformation to inhibit colorectal cancer. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway showed the highest enrichment. Compared with the blank group， the levels of TIPE1， p-PI3K， and p-Akt in M2 macrophages were significantly increased （P<0.05，P<0.01）. After treatment with Zuojinwan-containing serum， the levels of TIPE1， p-PI3K， and p-Akt were significantly decreased （P<0.05，P<0.01）. ConclusionZuojinwan may inhibit colorectal cancer proliferation and migration by suppressing M2 polarization of tumor-associated macrophages， which may be associated with inhibition of the PI3K/Akt signaling pathway in tumor-associated macrophages.

Objective:To evaluate the clinical effect of high-intensity interval training and moderate continuous aerobic training on patients classified as low risk for exercise rehabilitation after a percutaneous coronary intervention (PCI).Methods:A total of 43 patients considered low-risk after a PCI were randomly divided into a high-intensity interval training group (HIIT group, 22 cases) and a moderate continuous aerobic training group (MCT group, 21 cases). The HIIT group received high-intensity, but aerobic interval training involving 8 rounds of 3 minutes of high-intensity exercise with 2-minute intervals at 80% of peak power over 40 minutes, 3 times a week. The MCT group trained continuously at 60% of peak power for the same duration. After 12 weeks both groups were given an ultrasound examination and a cardiopulmonary exercise test to assess their cardiac functioning and exercise endurance. The subjects′ life quality was evaluated and compared using some items from the SF-36 scale.Results:Before the training, no significant differences were observed in the average left ventricular ejection fraction, stroke volume, peak power, peak oxygen uptake, anaerobic threshold, physiological functioning, physical pain, general health or social functioning between the two groups. After the training significant improvement in all these indicators was observed in both groups, but compared with MCT group, the average left ventricular ejection fraction, stroke volume, peak power and peak oxygen uptake of the HIIT group were significantly better.Conclusions:High-intensity, aerobic interval training is superior to moderate but continuous aerobic training for improving the cardiac functioning and exercise endurance of patients suitable for exercise rehabilitation after a PCI. But there is no significant difference in their effect on the short-term quality of life.

Using pancreatic polypeptide (PP) RIA kit prepared in our laboratory, serum levels of PP were observed in obese, type II diabetics with or without insulin treatment and 18 normal controls. The results showed that obese subjects presented hypersecretion of PP, hyperinsulinemia and hyperglycemia. Diabetics presented hypersecretion of PP with low levels of insulin and G-peptide. Possible explanations for hypersecretion of PP were commented.