ABSTRACT
Objective:To investigate the protective effect of human umbilical cord mesenchymal stem cell conditioned medium (HucMSC-cm) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and relevant mechanism of action.Methods:Forty 6-week-old male C57BL/6 mice were selected and randomized (random number) into the sham group, LPS group, LPS + HucMSC-cm (LPS+cm) group, and LPS+HucMSC-cm+Compound C (LPS+cm+cc) group, with 10 mice in each group. Mice were intratracheally injected with LPS (5 mg/kg) to establish ALI model, and intratracheally injected with hucMSC-CM (50 μL) 4 h after LPS treatment. Mice in the LPS+cm+cc group were intraperitoneally treated with Compound C (15 mg/kg) prior to LPS treatment. Neutrophils in peripheral blood were counted with the automated hematology analyzer 72 h after LPS administration. After that, mice were sacrificed, and the lung tissue pathology was observed using hematoxylin eosin (HE) staining. Besides, the expressions of IL-6, ICAM-1, VCAM-1 and P-AMP-activated protein kinase (P-AMPK) in the lung tissues were analyzed by Western blot and immunohistochemical assay. In vitro, human lung microvascular endothelial cells (HuLEC-5a) were cultured and divided into three groups: control group, LPS group (10 μg/ mL), and LPS + HucMSC-cm group. After 24 h of treatment, the expressions of p-AMPK and AMPK were detected by Western blot, and the expressions of IL-6 and IL-8 were detected by real-time fluorescence quantitative PCR. Oneway analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between two groups were performed using the Tukey’s multiple comparison test. Results:Compared with the sham group, the LPS group showed lungs with congestion and swelling, thickened pulmonary septum, and inflammatory cell infiltration. Moreover, in the LPS group, the protein expressions of IL-6 ( P=0.003), ICAM-1 ( P<0.001) and VCAM-1 ( P=0.001) were increased significantly, while the expression of p-AMPK was decreased ( P=0.013), accompanied by an increase in the proportion of neutrophils in peripheral blood ( P<0.001). Compared with the LPS group, the LPS+HucMSC-cm group demonstrated eased congestion, edema and pathological injury of lung tissue, reversed protein expressions of IL-6 ( P=0.003), ICAM-1 ( P=0.002), VCAM-1 ( P=0.006) and P-AMPK ( P=0.002), as well as decreased proportion of neutrophils in peripheral blood ( P<0.005). Compared with the LPS+HucMSC-cm group, the LPS+cm+cc group exhibited more severe lung histopathological injury, significantly increased protein expressions of IL-6, ICAM-1 and VCAM-1 in lung tissues, as well as decreased expression of P-AMPK protein. The results of immunohistochemistry were consistent with those of protein. In vitro experiment, after LPS treatment, the mRNA expressions of IL-6 ( P<0.001) and IL-8 ( P=0.027) were increased and p-AMPK protein expression ( P=0.005) was decreased as compared with the control group. In comparison with the LPS group, the LPS+HucMSC-cm group showed decreased mRNA expression levels of IL-6 ( P=0.003) and IL-8 ( P=0.002), but increased protein level of p-AMPK ( P=0.003). Conclusions:HucMSC-cm has a protective effect against LPS-induced acute lung injury, which is mainly attributed to the inhibited expression of adhesion molecules and inflammatory factors under the activation of AMPK.
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Objective:To analyze the influencing factors of prognosis of early mixed signet ring cell carcinoma (SRCC) of the stomach with signet ring cell ratio less than 50%.Methods:The clinical data of 110 patients with SRCC who underwent radical resection of gastric cancer in the First People's Hospital of Ziyang from January 2014 to December 2016 were retrospectively analyzed. The postoperative pathology was confirmed as mixed SRCC of the stomach with signet ring cell ratio less than 50%. The patients were followed up, and the end point of the follow-up was all-cause death. The prognostic influencing factors of SRCC patients were analyzed.Results:The median follow-up time was 32.5 months (0.9-70.0 months), with the median overall survival (OS) time of 40.0 months (7.0-61.0 months) and the 3-year OS rate of 46.5%. Kaplan-Meier survival analysis showed that the 3-year OS rate of age ≥60 years, male, upper stomach, tumor diameter ≥5 cm, invasion of the gastric wall, lymph node metastasis, and vascular invasion of mixed SRCC of the stomach patients was 34.3%, 31.1%, 30.0%, 33.3%, 40.7%, 28.9%, 37.5%, respectively, which was all lower than that of those with age <60 years old, female, lower stomach, tumor diameter <5 cm, non-invasive whole stomach wall, no lymph node metastasis, no vascular invasion (57.6%, 57.5%, 52.9%, 57.6%, 56.7%, 74.6%, 62.3%), and there was no statistically significant difference (all P < 0.05). Cox multivariate results showed that age ≥60 years old ( OR = 1.225, 95% CI 1.089-3.481, P = 0.003), lymph node metastasis ( OR = 1.077, 95% CI 1.059-2.674, P = 0.034), invasion of the whole stomach wall ( OR = 1.342, 95% CI 1.117-7.225, P = 0.002), and vascular invasion ( OR = 1.104, 95% CI 1.087-2.541, P = 0.018) were independent factors affecting OS of mixed SRCC of the stomach. Conclusion:Mixed SRCC of the stomach patients with signet ring cell ratio less than 50% featured by advanced age, lymph node metastasis, invasion of the full thickness of the stomach wall, and vascular invasion have a poor prognosis.
ABSTRACT
Objective To clinically verify the rationality of evaluation standard of oropharynx involvement in the Chinese 2008 staging system for nasopharyngeal carcinoma (NPC).Methods 333 consecutive patients with newly diagnosed,untreated,and nonmetastatic NPC were included.All patients had an MRI examnation of the nasopharynx and neck.The status of oropharynx involvement were evaluated.Results Of the 333 patients with NPC,26 (7.8 ％) patients presented with oropharynx involvement.Tumor invasion into oropharynx was highly related to tumor invasion into nasal cavity,parapharyngeal space,skull base,medial pterygoid muscle,paranasal sinuses,intracalvarium and masticator space excluding medial pterygoid muscle (P ＜ 0.050).The oropharynx involvement was associated with poorer 5-year overall survival (OS) and distant failure-free survival (DFFS) (38.1％ vs 72.6 ％,P＜ 0.001 and 49.1％ vs 84.5 ％,P＜ 0.001,respectively).By multivariate analyze,it was observed that oropharynx involvement was a significant predictive factor for OS and DFFS (P ＜ 0.001,P ＜ 0.001).Significant differences were observed in the 5-year OS (38.1％ vs 80.9 ％,P ＜ 0.001) and DFFS rates (49.1％ vs 89.3 ％,P ＜ 0.001) between the patients with oropharynx involvement and stage T2 patients.Conclusions MRI-evidenced oropharynx involvement had a negative impact on OS and DFFS in NPC patients.The oropharynx involvement is associated with poorer 5-year OS and DFFS compared with stage T2.The evaluation standard of oropharynx involvement for NPC in the Chinese 2008 staging system could be revised.