Objective To investigate the effect of acute physiology and chronic health evaluationⅡ ( APACHEⅡ) scoring system on evaluating the severity and prognosis in severe acute pancreatitis(SAP). Methods The APACHEⅡ scores were analyzed in 52 patients with SAP. Results The mean APACHEⅡ score of SAP was 16.60?9.07(8～40), and there were significant differences between the scores not only in Grade SAPⅠand Grade SAPⅡ(?

Objective To study the effect of Qige San ethyl acetate extract on the proliferation of human esophageal carcinoma Eca109 cells and to explore its possible mechanism. Methods Inhibitory effects of Qige San ethyl acetate extract on the proliferation of esophageal carcinoma Eca109 cells were detected by MTT assay, cell apoptosis was detected by flow cytometer, and the expression of protein STAT3, Bcl-2 and Caspase 9 was detected by Western blotting method. Results In the range of 10~100 μg/mL, Qige San ethyl acetate extract inhibited the proliferation of Eca109 cells effectively (P<0.05) . Compared with the control group, Qige San ethyl acetate extract in the concentrations of 1.47, 33.26, 75.52 μg/mL significantly increased the apoptotic rate of Eca109 cells within 48h ( P<0.01). And Western blotting results showed that the ex pression levels of STAT3 and Bcl-2 were reduced, and Caspase 9 was increased with the increase of drug concentration. Conclusion Qige San ethyl acetate extract could significantly inhibit the proliferation of Eca109 cells and induce cell apoptosis, and its mechanism is probably associated with the inhibition of signal transducers and activators of transcription 3 (STAT3) signaling pathway.

Objective:To screen the time points of high survival rate and efferocytosis dysfunction of rat alveolar macrophages stimulated by cigarette smoke extract (CSE), establish an in vitro model of alveolar macrophage efferocytosis function, and study chronic respiratory diseases with chronic inflammatory reaction as the main pathological changes. Methods:① Time point screening experiment: rat alveolar macrophages (NR8383 cells) were cultured in vitro, and the cells in logarithmic growth phase were divided into blank control group (100 μL complete medium) and 5% CSE group (90 μL complete medium + 10 μL 100% CSE). Alma blue method was used to detect the effect of 5% CSE on the activity of NR8383 cells at 6, 12, 24 and 48 hours. ② Apoptosis induction experiment: rat type Ⅱ alveolar epithelial cells (RLE-6TN cells) were cultured in vitro as phagocytic target cells of NR8383 cells, and the cells in logarithmic growth phase were divided into blank control group and 10, 30 and 60 minutes groups after ultraviolet exposure (apoptosis was induced by 30 000 μJ/cm 2 ultraviolet irradiation for 15 minutes). Flow cytometry was used to detect the apoptosis rate of RLE-6TN cells cultured for 10, 30 and 60 minutes after ultraviolet exposure. ③ Cell efferocytosis experiment: NR8383 cells in logarithmic phase were divided into blank control group and 5% CSE group. Two hours before NR8383 cells were stimulated by CSE for 6, 12 and 24 hours, RLE-6TN cells were exposed to ultraviolet to induce apoptosis, and the RLE-6TN cell suspension was added to NR8383 cells (the ratio of RLE-6TN cells to NR8383 cells was 5∶1). Flow cytometry was used to detect the efferocytosis rate of NR8383 cells to RLE-6TN cells at different time points treated with 5% CSE. Results:① Compared with the blank control group, the activity of NR8383 cells significantly decreased after treatment with 5% CSE for 48 hours [cell reduction rate: (68.5±4.1)% vs. (73.6±2.3)%, P < 0.05]. However, there were no significant differences when the activities of NR8383 cells treated with 5% CSE for 6, 12 and 24 hours were compared with the blank control group, so these three time points were selected for the subsequent establishment of alveolar macrophage cell efferocytosis dysfunction in vitro model experiment. ② Compared with the blank control group, the apoptosis rate of RLE-6TN cells significantly increased at 10, 30 and 60 minutes after ultraviolet exposure [(66.87±8.63)%, (85.51±2.39)%, (96.13±2.74)% vs. (9.13±3.17)%, all P < 0.01] in a time-dependent manner. Considering that it taked about 50 minutes for RLE-6TN cells to be labeled with PKH26 membrane labeling probe, 10 minutes after ultraviolet exposure was selected to label RLE-6TN cells. ③ Compared with the blank control group, the efferocytosis function of NR8383 cells was significantly decreased after treatment with 5% CSE for 12 hours [cell efferocytosis rate: (33.64±1.30)% vs. (44.02±2.71)%, P < 0.01], but there was no significant effect on the efferocytosis function of NR8383 cells at 6 hours and 24 hours. Conclusions:CSE can induce alveolar macrophage cell efferocytosis dysfunction. Based on the test results of the effect of 5% CSE on NR8383 cell activity and cell efferocytosis function, 12 hours with high survival rate and weak efferocytosis effect of NR8383 cells can be selected as the in vitro model condition of alveolar macrophage cell efferocytosis dysfunction.

Objective To investigate the progression of breast cancer in mice induced by chronic binding stress and the regulatory mechanism of Xiaoyao SAN based on TGF-β1/CD147 signal pathway.Methods 40 BABL/c mice were randomly divided into tumor group,model group,Xiaoyaosan group and Mifepristone group,and then 4T1 cell line was inoculated into the armpits of each group of mice.After Tumor formation,mice in all groups except tumor group were subjected to chronic restraint stress for 21 days.Meanwhile,mice in Xiaoyaosan and Mifepristone groups were gavaged with the corresponding drugs,and mice in the other two groups were gavaged with normal saline.After the modeling,the mice were sacrificed after anaesthesia.The weight and volume of the tumors and visceral index of the mice were measured.The contents of serum tumor markers(CA199,CEA,VEGF),serum neurotransmitters(DA and CORT),and inflammatory mediators(TGF-β1 and IL-10)in tumor tissues were detected by Elisa.The expressions of iNOS and Arg-1,the polarization markers of macrophages,and the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF in tumor tissues were all detected by immunohistochemistry and Western blot.Results Compared with tumor group,in model group,tumor weight and volume,serum CA199,CEA,VEGF,CORT content,tumor TGF-β1 and IL-10 content were significantly increased;visceral index and serum DA content were significantly reduced;the expression of M2-type polarization marker Arg-1 in tumor macrophages was significantly increased,while the expression of M1-type polarization marker iNOS was significantly decreased;the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF were significantly increased.Both Xiaoyaosan and mifepristone could effectively reverse the above changes.Conclusion The mechanism of chronic restraint stress promoting breast cancer progression in mice is related to the increased release of TGF-β1 from M2-type polarization of tumor-associated macrophages,which activates CD147 and its downstream related signals.Xiaoyaosan could relieve the M2-type polarization of macrophages caused by increased corticosterone under stress conditions,reduce the production of TGF-β1,inhibit CD147 and its downstream signal,and thus inhibit the progression of breast cancer caused by chronic restraint stress in mice.

Objective:To observe the effects of Xiaoqinglong Decoction and Qingqi Huatan Pills on interleukin-1β(IL-1β)-induced mucushypersecretion model of human airway epithelial H292 cellsand related molecules of nuclear factor-κB/microRNA-494 (NF-κB/miR-494) signaling pathway, and to explore the mechanism of the two medicines in improving pathological airway mucus.Methods:Methyl thiazolyl tetrazolium (MTT) colorimetric method was used to detect the effects of different concentrations of Xiaoqinglong Decoction and Qingqi Huatan Pills on the activity of H292 cellsinduced by IL-1β, and the appropriate concentration was selected for subsequent experiments. Cells were randomly divided into blank group, IL-1β model group (5 μg/L IL-1β), NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) group (5 μg/L IL-1β+100 μmol/L PDTC), Xiaoqinglong Decoction (5 μg/L IL-1β+1 000 mg/L Xiaoqinglong Decoction) and Qingqi Huatan Pill group (5 μg/L IL-1β+1 000 mg/L Qingqi Huatan Pills). 5 μg/L IL-1β was used to induce H292 cells for 24 hours to establish a model of airway epithelial mucus hypersecretion. Enzyme linked immunosorbent assay (ELISA) method was used to detect the levels of mucin 5AC (MUC5AC), tumor necrosis factor-α (TNF-α) and IL-8 and the synthesis of intracellular MUC5AC and cystic fibrosis transmembrane conductance regulator (CFTR). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of MUC5AC mRNA, CFTR mRNA, miR-494. Western blotting was used to detect protein expression of key proteins (p65) and NF-κB inhibitors (IκB) in NF-κB signaling pathway.Results:Xiaoqinglong Decoction and Qingqi Huatan Pills with the concentration of 1 000 mg/L were selected for the follow-up experiment. Compared with the blank group, the levels of MUC5AC, TNF-α and IL-8 were significantly increased in the model group, intracellular MUC5AC protein content and mRNA expression were also significantly increased, intracellular CFTR protein content and mRNA expression were significantly decreased, and intracellular p65 protein expression was significantly up-regulated, the expression of IκB protein was significantly down-regulated, and the expression of miR-494 was significantly increased. Compared with the model group, the levels of MUC5AC, TNF-α and IL-8 were significantly reduced in PDTC group, Xiaoqinglong Decoction group and Qingqi Huatan Pill group, intracellular MUC5AC protein content and mRNA expression were also significantly decreased, and intracellular p65 protein expression was significantly down-regulated, and IκB protein expression was significantly up-regulated, miR-494 expression was significantly reduced. Intracellular CFTR protein content and mRNA expression were significantly increased in both PDTC group and Qingqi Huatan Pill group. Compared with the PDTC group, the level of TNF-α in the Xiaoqinglong Decoction group was significantly increased (ng/L: 22.77±3.14 vs. 11.09±3.37, P < 0.05), the content and mRNA expression of CFTR and IκB protein expression was significantly decreased [CFTR protein (ng/L): 97.38±6.62 vs. 227.04±19.48, CFTR mRNA (2 -ΔΔCt): 0.99±0.08 vs. 1.21±0.08, IκB/β-actin: 1.69±0.11 vs. 2.00±0.18, all P < 0.05], the level of TNF-α in Qingqi Huatan Pill group was significantly higher (ng/L: 19.08±3.71 vs. 11.09±3.37, P < 0.05). Compared with Xiaoqinglong Decoction group, the protein content and mRNA expression of CFTR and IκB protein expression in Qingqi Huatan Pill group were significantly increased [CFTR protein (ng/L) : 235.01±22.71 vs. 97.38±6.62, CFTR mRNA(2 -ΔΔCt): 1.32±0.15 vs. 0.99±0.08, IκB/β-actin: 1.94±0.16 vs. 1.69±0.11, all P < 0.05]. Conclusions:The effect of Xiaoqinglong Decoctionin improving the hypersecretion of mucus in the airway epithelium may be related to the inhibition of NF-κB/miR-494 inflammatory signal-mediated MUC5AC hypersecretion, while the effect of Qingqi Huatan Pills may be related to the inhibition of NF-κB/miR-494 inflammatory signal-mediated MUC5AC hypersecretion and CFTR dysfunction. Therefore, the difference in the mechanism of the two treatments of airway pathological mucus is mainly in the regulation of CFTR mRNA and protein.

Pathological mood changes,mainly depression,occurring during the diagnosis and treatment of breast cancer are referred to as breast cancer-related depression(BCRD).Numerous epidemiological and clinical studies have confirmed that BCRD is a complex condition that is difficult to treat and has a poor prognosis.Most existing clinical treatments involve the use of postoperative chemotherapy for breast cancer,and antidepressant drugs,which treat breast cancer and depression as two independent diseases and have various disadvantages such as low efficiency and strong adverse reactions.Traditional Chinese Medicine(TCM)has a unique value in the prevention and treatment of BCRD via its ability to regulate multiple pathways and targets using multiple components at the same time.In this paper,we review the mechanism of BRCD and the therapeutic mechanisms of TCM from the aspects of neurological disorders,inflammatory immune response,and intestinal flora disorders,with a view to providing references for the clinical application and research of TCM in the treatment of BCRD.

Objective To study the core behavioral symptoms,biological indicators,and pathological changes of a mouse model of breast cancer complicated with depression induced using 4T1 breast cancer cell inoculation combined with chronic restraint stress(CRS).Methods BABL/c mice were randomly divided into Control,Stress,Tumor,and stress combined with tumor(S+T)groups.Mice in the tumor and S+T groups were inoculated under the front legs with breast cancer 4T1 cells.After tumor formation,mice in the stress and S+T groups were subjected to CRS for 21 days.The body weight and food intake of each group were monitored during modeling.After the experiment,the occurrence of depression-like behavior of mice in each group was evaluated by sucrose preference test,open field test,elevated plus-maze test,and forced swimming test.After the mice were decapitated,the weights and volumes of the tumors were measured.Concentrations of serum tumor markers,including carbohydrate antigen(CA199),carcinoembryonic antigen(CEA),and vascular endothelial growth factor(VEGF),and related neurotransmitters,including 5-hydroxytryptamine(5-HT),norepinephrine(NE),and corticosterone(CORT),were determined using ELISA.HE staining was used to observe histopathological changes to the hippocampus and tumor.Results In S+T group mice,body weight and food intake were significantly decreased,tumor weight and volume were significantly increased,serum tumor marker(CA199,CEA,VEGF)levels were significantly increased,enthusiasm and desire to explore a new environment were reduced,stress and despair behaviors were significantly increased,and levels of the serum neurotransmitters 5-HT and NE and levels of CORT were significantly increased.In addition,the cell arrangement in the tumor tissue was loose,the amount of intercellular substance decreased,the pathological nuclear classification phase was increased,the arrangement and morphology of neurons in the CA3 region of the hippocampus were disordered,and there were obvious nuclear vacuolation-like changes.Conclusions A mouse model of breast cancer complicated with depression induced by 4T1 breast cancer cell inoculation combined with CRS showed the typical dual symptoms and biological indicators of breast cancer and depression and can be used as a good reference model for experimental studies of breast cancer complicated with depression.