Objective To screen the potential biomarkers in plasma of rats with acute paraquat (PQ) poisoning using gas chromatography-mass spectrometry (GC-MS) based metabonomics technology,and to provide concrete evidence for early diagnosis.Methods Eight Sprague-Dawley (SD) rats were randomly divided into PQ poisoning group (intragastricly administrated with PQ solution 100 mg/kg) and control group (intragastricly administrated with the same volume of normal saline) according to the random number table,with 4 rats in each group.The general situation of rats was observed at 2,24 and 48 hours after administration.The blood of eye sockets was collected,the endogenous small molecule metabolites in plasma were determined with GC-MS method,and metabolic profile analysis and random forest analysis were performed to filter the potential biomarkers.Results ① The rats in PQ poisoning group gradually appeared lack movement,tachypnea,abdominal seizure and other symptoms of poisoning.In control group,the vital signs were stable.② The metabolites in plasma of rat were analyzed with GC-MS analysis,and the diagrammatic figure was plot as combined with principal component analysis (PCA) and partial least squares-discriminated analysis (PLS-DA) model,which showed that the distribution of plasma metabolism in PQ poisoning group was more diffuse but in the control group was more intensive,indicating that the metabolic patterns in two groups were different.From 2 hours after PQ administration,the metabolic trajectory in PQ poisoning group was significantly deflected compared with that of the control group,which was similar to control group until 48 hours,indicating that the metabolites in plasma of rat showed obvious difference in the early period.Five kinds of potential biomarkers with large weights were selected by random forest method which were serine,L-asparagine,hexadecanoic acid,octadecanoic acid,and arachidonic acid,the retention time was 15.259,24.345,33.334,37.695,and 40.254 minutes,respectively.The levels of serine,L-asparagine,arachidonic acid in PQ poisoning group were significantly higher than those of the control group,peaked at 48,48 and 24 hours,respectively (40.884-5.38 vs.28.85±2.32,6.61±1.31 vs.0.76±0.65,14.21±4.28 vs.4.42±1.19,all P ＜ 0.01),and the levels of hexadecanoic acid and octadecanoic acid were significantly lowered,reached tough at 48 hours (39.09 ± 10.23 vs.83.99 ± 20.49,44.03 ± 3.60 vs.140.76 ± 73.91,P ＜ 0.05 and P ＜ 0.01).The changes in these biomarkers were related to the toxicity of PQ,indicating that PQ could interfere the energy and lipid metabolism in rats.Conclusion Combine with the metabonomics analysis,screened plasma serine,L-asparagine,arachidonic acid content in PQ poisoning rats increased significantly,and hexadecanoic acid and octadecanoic acid content decreased significantly,which can preliminary diagnose acute PQ poisoning with animal general performance.

Objective To analyze the clinicopathological factors on the prognosis and investigate the necessity of adjuvant chemotherapy for patients with stage Ⅱ colorectal cancer.Methods The clinical data of 255 patients with stage Ⅱ colorectal cancer who were admitted to the First Affiliated Hospital of Sun Yat-Sen University from January 2000 to December 2005 were collected.The survival curve was drawn by Kaplan-Meier method,and the survival rate of the patients were analyzed by Log-rank test.Factors influencing the survival were analyzed by Cox regression model.Results All patients were followed up till April 23,2010,and the mean time of follow-up was (63 ± 22)months.The median survival time was 63 months.The 5-year and tumor-free survival rates were 85.3％ and 83.7％,respectively.The 5-year overall and tumor-free survival rates of patients without preoperative bowel obstruction or perforation were 86.9％ and 85.6％,which were sigaificantly higher than 72.7％and 68.4％ of patients with preoperative bowel obstruction or perforation(x2 =4.546,4.573,P ＜ 0.05 ).The 5-year overall and tumor-free survival rates of patients with negative resection margin were 85.5％ and 83.9％,which were significantly higher than 75.0％ and 75.0％ of patients with positive resection margin(x2 =7.020,6.009,P ＜ 0.05 ).The result of multivariate analysis revealed that preoperative bowel obstruction or perforation were the independent risk factors for patients with stage Ⅱ colorectal cancer(Wald =4.477,relative risk =2.371,95 ％ confidence interval:1.066-5.275,P ＜ 0.05 ).The 5-year overall and tumor-free survival rates were 87.3％ and 86.0％ for patients who received adjuvant chemotherapy,and were 82.2％ and 80.3％ for patients who did not receive adjuvant chemotherapy (P ＞ 0.05 ).Conclusions Preoperative bowel obstruction or perforation are independent risk factors for the survival of patients with stage Ⅱ colorectal cancer.Adjuvant chemotherapy could not improve the prognosis of patients with stage Ⅱ colorectal cancer.

Objective:To investigate the application value of ambulatory surgery mode in inguinal hernia repair.Methods:The retrospective and descriptive study was conducted. The clinical data of 416 patients with inguinal hernia who were admitted to the Meishan People′s Hospital, West China Hospital of Sichuan University from January 2020 to January 2022 were collected. There were 374 males and 42 females, aged 52(range, 25-70)years. All patients underwent inguinal hernia repair with the ambulatory surgery mode. Observation indicators: (1) surgical situations; (2) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. Of the 416 patients, 258 patients underwent laparoscopic transabdominal preperitoneal inguinal hernia repair (TAPP) under general anesthesia and 158 patients underwent open inguinal hernia repair under local anesthesia (98 cases of Lichtenstein repair and 60 cases of preperitoneal repair). The intraoperative measured diameter of hernia ring defect and operation time of the 416 patients were 1.9 (range, 0.9-3.2)cm and 52 (range, 35-80)minutes. The duration of hospital stay of the 416 patients <48 hours, including 395 cases with the duration of hospital stay <24 hours. There were 21 patients with delayed discharge including 12 cases as post-operative pain, 8 cases as adverse reactions to general anesthesia, and 1 case as postoperative seroma. (2) Follow-up. All 416 patients were followed up for 12 months after surgery. During the follow-up period, there was no serious complication such as recurrent inguinal hernia, wound infection, intestinal fistula or obstruction. At 1 month after surgery, ultrasound examination of the inguinal area did not reveal any serum swelling or seroma. The postoperative visual analogue scale of pain in patients undergoing laparoscopic TAPP was 2.70±0.10 at postoperative 3 days and 0 at postoperative 12 months. The above indicator in patients undergoing Lichtenstein repair and pre-peritoneal repair was from 3.20±0.20 and 3.00±0.10 at postoperative 3 days to 0 and 0 at post-operative 12 months, respectively. All patients did not experience chronic pain for more than 3 months. All 416 patients conducted satisfaction surveys over the phone, and all of them were very satisfied or satisfied, with a satisfaction rate as 100.00%(416/416).Conclusion:Ambulatory surgery mode in inguinal hernia repair is safe and feasible.

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg^-1 bleomycin and orally administered with 30 mg·kg^-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.
Animals ; Mice ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; MAP Kinase Signaling System ; Alkaloids/pharmacology* ; Fibroblasts ; Macrophages/metabolism*