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Objective:To explore the effect and mechanism of cytochrome P450 1A1 (CYP1A1) on regulating phagocytosis of macrophage treated with Escherichia coli ( E.coli). Methods:① The mouse leukemia cells lines of monocyte macrophage RAW264.7 (RAW) were cultured in vitro and treated with 30 multiplicity of infection (MOI) dosages of E.coli for 40 minutes, glycerin control group was set up to observe the change of CYP1A1 during infection. ② The RAW cells with CYP1A1 overexpression (CYP1A1/RAW) and knock out (CYP1A1 KO/RAW) were cultured in vitro and treated with 30 MOI E. coli for 40 minutes, while the negative controlled RAW cells (NC/RAW) were established as control to observe the relationship between cell phagocytosis and CYP1A1 expression, and the effect of CYP1A1 on phagocytic receptor [scavenger receptor-A (SR-A)] and its signal pathway [mitogen-activated protein kinase (MAPK) pathway]. ③ NC/RAW and CYP1A1 KO/RAW cells were cultured in vitro and pretreated with 1 μmol/L extracellular signal-regulated kinase (ERK) inhibitor (U0126) for 2 hours, and then treated with 30 MOI E.coli for 40 minutes, phosphate buffered solution (PBS) control group was set up to observe whether the effect of CYP1A1 on phagocytosis through controlled the MAPK pathway. ④ The RAW cells were cultured in vitro and pretreated with 100 nmol/L CYP1A1 hydroxylase active product 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] for 2 hours, and then treated with 30 MOI E.coli for 40 minutes, and PBS control group was set up to observe whether the effect of CYP1A1 on phagocytosis was related to CYP1A1 hydroxylating metabolite. ⑤ The RAW cells with overexpression CYP1A1 hydroxylase-activity mutation (CYP1A1m/RAW) were cultured in vitro and treated with 30 MOI E.coli for 40 minutes, the CYP1A1/RAW cells were set up as control group to observe whether the effect of CYP1A1 on phagocytosis was related to CYP1A1 hydroxylase-activity. Results:① Compared with glycerin control group, CYP1A1 mRNA expression was significantly increased by E.coli stimulation (2 -ΔΔCt: 7.79±0.71 vs. 1.00±0.00, P < 0.05), indicating that CYP1A1 might participate in regulating infection progress. ② Compared with NC/RAW cells, the number of E.coli colonies phagocytized by CYP1A1/RAW cells was significantly decreased after 40 minutes of E.coli stimulation (×10 3 CFU/mL: 4.67±3.06 vs. 15.67±5.03, P < 0.05), while CYP1A1 KO/RAW cells had a significant increase in the number of E.coli colonies phagocytized (×10 3 CFU/mL: 46.00±5.29 vs. 15.67±5.03, P < 0.05), suggesting that CYP1A1 might negatively control macrophage phagocytosis function. Meanwhile, compared with NC/RAW cells, the expression of SR-A mRNA in CYP1A1/RAW cells was significantly down-regulated (2 -ΔΔCt: 0.31±0.03 vs. 1.00±0.00, P < 0.05), and the activation level of ERK was significantly reduced. However, the expression of SR-A mRNA in CYP1A1 KO/RAW cells was significantly up-regulated (2 -ΔΔCt: 3.74±0.25 vs. 1.00±0.00, P < 0.05), and the activation of ERK was enhanced, indicating that CYP1A1 could negatively regulate phagocytic receptors and their signaling pathways.③ Compared with PBS, U0126 pretreatment significantly inhibited the CYP1A1 knockout induced upregulation of SR-A mRNA expression (2 -ΔΔCt: 0.62±0.05 vs. 4.38±0.39, P < 0.05) and ERK activation, and inhibited the enhancement of phagocytosis in macrophages induced by CYP1A1 knock out [ E.coli colonies phagocytized by cells (×10 3 CFU/mL): 12.67±1.15 vs. 45.33±4.16, P < 0.05], suggesting that CYP1A1 inhibited macrophage phagocytosis function by regulating ERK activation. ④ Compared with PBS, the phagocytosis of RAW cells pretreated with 12(S)-HETE did not change significantly [ E.coli colonies phagocytized by cells (×10 3 CFU/mL): 17.00±1.00 vs. 16.33±2.52, P > 0.05], suggesting that CYP1A1 might not control phagocytosis function by its hydroxylase-activity metabolism 12(S)-HETE. ⑤ Compared with CYP1A1/RAW cells, there was no significant change in the phagocytic function of CYP1A1m/RAW cells [ E.coli colonies phagocytized by cells (×10 3 CFU/mL): 3.67±1.15 vs. 3.33±0.58, P > 0.05], suggesting that CYP1A1 might not control phagocytosis function by its hydroxylase-activity. Conclusion:CYP1A1 can negatively regulate the phagocytosis of macrophages by inhibiting the activation of ERK and reducing the expression of SR-A, but this regulatory effect is not related to the activity of CYP1A1 hydroxylase and its pro-inflammatory metabolism 12(S)-HETE.
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Sepsis remains the leading cause of late death in trauma patients. Many bottleneck problems in the field of post-traumatic sepsis research have not been solved, which are mainly reflected in the lag of early warning research, limited preventive interventions and unclear diagnostic criteria. The authors focus on the early warning of sepsis, preventive intervention measures and early diagnostic criteria to guide the clinical positive response so as to reduce the late mortality caused by post-traumatic sepsis and improve the overall level of trauma treatment.
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Objective To analyze the etiology of pseudoachalasia.Methods Patients who were diagnosed as having pseudoachalasia in Endoscopy Center of The Affiliated Zhongshan Hospital of Fudan University from September 2010 to June 2015 were retrospectively analysed.Results A total of 12 patients were enrolled in this study,6 males and 6 females.The median age,median disease duration and median Eckcardt score was 54.5(24.0～71.0) years old,2.5(0.2～ 10.0) years and 4(3～9),respectively.Seven cases were caused by malignant tumors,2 had benign tumors,and 3 peptic stricture.Conclusion The most common cause of pseudoachalasia is malignant tumors.Accurate diagnosis relies on the comprehensive medical history and complete examinations.
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Objective The objectives of this study were to analyze the results of lung cancer screening from 9265 urban residents in Urumqi from year 2014 to 2016,and to evaluate the significance of early diagnosis and treatment of cancer for the lung cancer prevention.Methods A total of 31,177 people with high risk of lung cancer were assessed by cancer risk questionnaire surveyed from 40 to 69 years old residents in Urumqi.High-risk groups were assigned to low-dose spiral CT scan in Affiliated Tumor Hospital of Xinjiang Medical University.Results 9,265 people were scanned with low dose spiral CT and overall completion rate was 29.7％.There had 11.9％ detection rate in 1,005 people who were scanned positive pulmonary nodules.The detection rate was 31.9％ for 2,955 people who were scanned solid nodules(＜5 mm) and 2.5％ for 236 people who had the non solid nodules(＜ 8 mm).After screening,14 patients were diagnosed by pathology and the detection rate was 0.2％.The emphysema,pulnonary cysts,pulmonary bullae and other related lung disease were detected in 4,095 people and the detection rate was 44.2％.Conclusion The lung health status of Urumqi residents was found by a wide range of lung cancer screening,and the awareness of lung cancer prevention and control was greatly improved.It provided the basis for the establishment of effective prevention and treatment system,which was helpful to improve the early diagnosis and treatment rate of lung cancer.
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Objective To explore the clinical effect of endoscopic retrograde cholangiopancreatography (ERCP) for elderly patients with periampullary diverticula accompanied with choledocholithiasis.Methods The retrospective cross-sectional study was conducted.The clinical data of 297 elderly patients with age ＞70 years and periampullary diverticula accompanied with choledocholithiasis who were admitted to the Zhongshan Hospital affiliated to Fudan University between January 2013 and January 2016 were collected.All the patients received lithotomy by ERCP after completion of preoperative preparation,and then underwent symptomatic treatment.Observation indicators included:(1) treatment results:cannulation time,success rate of cannulation and success rate of stones removed;(2) surgical complications:hemorrhage,perforation and pancreatitis;(3) follow-up results.All patients were followed up by outpatient examination and telephone interview up to December 2016.Follow-up included postoperative delayed perforation,patients' survival,further attack of acute cholangitis and reoperation for removing stones.Measurement data with normal distribution were represented as x ± s,and measurement data with skewed distribution were described as M (range).Results (1) Treatment results:all the 297 patients underwent successful lithotomy by ERCP,with a cannulation time of (5±4)minutes and a success rate of cannulation of 100.00％ (297/297).Of 297 patients,292 had one-off success of stones removed,with a one-off success rate of 98.32％ (292/297),and 5 received partial stones removed due to choledocholithiasis combined with acute cholangitis.(2) Surgical complications:4 patients were complicated with immediate hemorrhage during intraoperative endoscopic sphincterotomy (EST).Bleeding of 1 patient was cauterized by biopsy forceps,and 3 patients had simplex JHY-BAL compression hemostasis.Two patients with postoperative delayed hemorrhage had successful hemostasis by biopsy forceps with metal hemostatic clip under endoscope after emergency duodenoscopy.One patient with intraoperative perforation was cured by conservative treatment.Two patients with severe acute pancreatitis underwent continuous gastrointestinal decompression combined with maintenance therapy of somatostatin,and then received endoscopic ultrasound-guided puncture and drainage for pseudocyst around the pancreas,with a stable symptoms of pancreatitis after 4 weeks.(3) Follow-up results:all the 297 patients were followed up for 6-12 months,with a median time of 8 months.During follow-up,292 patients had healthy survival,without recurrences of cholangitis and bile duct stone,and no delayed perforation and death were detected.Five patients underwent the second time lithotomy by ERCP after 2-3 months postoperatively.Conclusion Lithotomy by ERCP is safe and effective in the treatment of elderly patients with periampullary diverticula accompanied with choledocholithiasis.
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Objective To study the value of endoscopic treatment for patients with gastric submucosal tumor ( G-SMT ) . Methods The data of 1663 patients with G-SMT undergoing endoscopic treatment was retrospective reviewed from January 2008 to December 2013. Patients′ demographics, treatment outcomes, and follow-up were evaluated. Results A total of 1671 lesions of G-SMT were included in the study. The mean maximum size of lesions was (1. 50±1. 02) cm. Twenty lesions were treated by endoscopic mucosal resection, 296 lesions by endoscopic submucosal dissection (ESD), 7 lesions by ESD+nylon endoloop, 1011 lesions by endoscopic submucosal excavation, 44 lesions by submucosal tunneling endoscopic resection, and 285 lesions by endoscopic full-thickness resection. Endoscopic treatment failed in 8 cases. Postoperative pathology diagnosis included 554 liomyoma, 485 gastrointestinal stromal tumors, 160 ectopic pancreas, and other such as lipoma, neuroendocrine tumor and fibroma. There were 16 cases of bleeding and 18 cases of perforation after treatment. Except for 4 cases of bleeding and 2 cases of perforation underwent additional surgical procedures, all patients were managed by conservative treatments. During a median follow-up time of 36 months of 1226 cases, the recurrence rate was 1％( 12/1226) ,and no death occurred. Conclusion Endoscopic treatment is safe and effective in treating G-SMT for long-term outcomes.
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Objective To study the anti-inflammatory effects of idazoxan (IDA) on endotoxin lipopolysaccharide (LPS) challenged mice in vivo and activated macrophages in vitro,and explore its potential molecular mechanisms.Methods To do the experiments in vivo,30 adult male C57BL/6 mice were randomly divided into control group,model group,and low,medium and high doses IDA groups (IDA-L,IDA-M,and IDA-H groups),n =6 in each group.The inflammatory model was reproduced by intraperitoneal injection of LPS 10 mg/kg,and the control group was injected with the same amount of normal saline.The IDA groups received LPS (10 mg/kg) and IDA 0.3,1.0 and 3.0 mg/kg,respectively.The blood samples of mice in each group were collected at 6 hours after the reproduction of the model.For the in vitro experiments,primary peritoneal macrophages were collected from 20 adult male C57BL/6 mouse cells and they were divided into control group,LPS group (10 mg/L) and LPS+IDA-L,IDA-M,IDA-H groups (10 mg/L LPS + 5,25,100 μmol/L IDA,respectively).Cell culture supernatants were collected at 24 hours after the reproduction of the model.Detection methods:enzyme linked immunosorbent assay (ELISA) was used to determine the levels of serum tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO).Western Blot was used to determine the effect of IDA on the expression levels of nuclear factor-κB (NF-κB) in macrophages.Results ① For the in vivo experiment,the serum levels of TNF-α and IL-6 were significantly elevated in the model group as compared with those in the control group [TNF-o (ng/L):403.96 ± 40.98 vs.17.50 ± 8.68;IL-6 (ng/L):61 400.31 ± 7 826.61 vs.2 436.30 ± 448.89;both P ＜ 0.01].IDA treatment could inhibit the elevation of inflammatory cytokines in a dose-dependent manner,with the most significant decrease in LPS+IDA-H group [TNF-α (ng/L):170.09 ± 28.53 vs.403.96 ± 40.98,IL-6 (ng/L):16 570.81 ± 1 083.65 vs.61 400.31± 7 826.61;both P ＜ 0.01].② For the in vitro experiment,the levels of TNF-α,IL-6,MCP-1,and NO secreted by LPS-stimulated macrophages were distinctly higher in the LPS group than those in the control group [TNF-α (ng/L):7 259.14 ± 320.70 vs.28.50±27.08,IL-6 (ng/L):14809.60±5852.73 vs.1 113.47±465.53,MCP-1 (ng/L):20847.37± 1 788.33 vs.447.37± 395.69,NO (μmol/L):1 900.00 ± 144.31 vs.603.03 ± 102.18;all P ＜ 0.01].However,IDA intervention could lower the secretion of TNF-α,IL-6,MCP-1 and NO in a dose-dependent manner,with the most notable decrease in the LPS+IDA-H group [TNF-α (ng/L):784.40±281.90 vs.7259.14±320.70,IL-6 (ng/L):1 802.96± 1 534.18 vs.14 809.60± 5 852.73,MCP-1 (ng/L):2005.26± 1 534.28 vs.20847.37 ± 1 788.33,NO (μ mol/L):654.54± 150.21 vs.1 900.00 ± 144.31;all P ＜ 0.05].In addition,IDA at the concentration of 100 μmol/L could promote the translocation of NF-κBp65 in macrophages into the nucleus 15 minutes early and lead to increased NF-κBp65 expression (gray value:18.70 ± 2.29 vs.1.09 ± 0.36,P ＜ 0.05),hut significantly reduce the expression levels of NF-κBp50 in the nucleus at 45 minutes after treatment (gray value:1.99 ± 0.14 vs.2.94 ± 0.54,P ＜ 0.05).Conclusions IDA could significantly reduce inflammation of mice challenged with LPS and inhibit inflammatory cytokines and mediators secreted by macrophage in a dose-dependent manner.High concentration of IDA (100 μmol/L) exhibited the greatest anti-inflammatory effects.The anti-inflammatory effect of IDA may be worked through NF-κB signaling pathway.
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<p><b>OBJECTIVE</b>To investigate the impact of additional gastrectomy after endoscopic submucosal dissection(ESD) on the prognosis of early gastric cancer.</p><p><b>METHODS</b>Clinical data of 107 early gastric cancer patients undergoing additional gastrectomy after ESD (research group, n=44) or radical surgery (control group, n=63) from January 2008 to December 2014 in Zhongshan Hospital were retrospectively analyzed. The reasons for additional gastrectomy after ESD included positive resection margin (n=10), lymphovascular invasion (n=5), well-differentiated mucosal tumor with a diameter >3 cm (n=10), poor-differentiated mucosal tumor with a diameter >2 cm (n=4), submucosal tumor(sm1) with a diameter >3 cm (n=10), and submucosal tumor(sm2) (n=9). Operation time, length of stay, lymph node metastasis, tumor recurrence and disease-free survival rate were compared between two groups.</p><p><b>RESULTS</b>Baseline data of two groups were not significantly different (all P>0.05). After evaluation, absolute and relative indications were identified in 19 cases (43.2%) and 25 cases (56.8%) of research group, and in 28 cases (44.4%) and 35 cases(55.6%) of control group without significant difference (P=0.897). Lymph node metastasis occurred in 6 patients (4.5%) after surgery in research group and 6.3% in control group (P=0.690). Operation time was (218.5±74.3) minutes in research group and (219.8±81.8) minutes in control group (P=0.932). Length of stay was (10.0±12.3) days in research group and (10.8±9.9) days in control group (P=0.687). Follow-up time was (35.5±15.0) months in research group and (29.5±18.1) months in control group (P=0.072). Tumor recurrence rate was 4.5% in research group and 9.5% in control group (χ(2)=0.928, P=0.229). Mortality was 4.5% in research group and 7.9% in control group (χ(2)=0.487, P=0.485). Besides, no significant differences of operation mode (P=0.164), lymphatic clearance mode (P=0.330), number of harvested lymph node (P=0.467), morbidity of postoperative infection or fever (P=0.923) were found. Three-year tumor-free survival rate was 95.5% and 89.2% in research and control group respectively without significant differences (P=0.571).</p><p><b>CONCLUSION</b>Additional gastrectomy after endoscopic submucosal dissection has no negative influence on the prognosis of patients with early gastric cancer, whose efficacy is similar to simple radical gastrectomy.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Disease-Free Survival , Early Detection of Cancer , Endoscopic Mucosal Resection , Gastrectomy , Methods , Gastric Mucosa , Lymph Nodes , Lymphatic Metastasis , Lymphatic Vessels , Neoplasm Recurrence, Local , Operative Time , Prognosis , Retrospective Studies , Stomach Neoplasms , General Surgery , Survival RateABSTRACT
Objective To evaluate the efficacy of a new endoscopic suturing device(OverStitchTM, Apollo Endosurgery, USA)for gastrointestinal wall defect after endoscopic full?thickness resection (EFTR). Methods Clinical data of the patients with submucosal tumors who underwent endoscopic suturing closure of gastrointestinal wall defect at the Endoscopy Center of Zhongshan Hospital from April 2015 to June 2015 were retrospectively analyzed. Results Five patients were included in this research with 4 lesions located in stom?ach and 1 lesion located in descendent duodenum. The mean diameter of lesions was 3?? 2 cm (ranging 2?? 0?5?? 0 cm). All patients underwent complete closure and none of them was converted to laparoscopic surgery or laparotomy. The mean repairing time was 16?? 6 min (ranging 11?? 0?22?? 0 min). The mean postoperative hospi?talization time was 5 days ( ranging 4?6 d). Two patients complained about slight abdominal pain and elevated body temperature. CT showed minor pleural effusion in one case. These patients received antibiotics, were on gastrointestinal decompression and asked to maintain the semi?supine position and discharged after 3 to 4 days. Conclusion Endoscopic suturing closure of gastrointestinal wall defect with the OverStitchTM en?doscopic suturing device is technically fast, feasible and safe.
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<p><b>OBJECTIVE</b>To determine the feasibility and efficacy of endoscopic submucosal dissection(ESD) in treating early gastric cancer(EGC) and precancerous lesions in the remnant stomach of patients after gastrectomy.</p><p><b>METHODS</b>Clinical data of 36 patients with EGC and precancerous lesions in remnant stomach undergoing ESD in Endoscopy Center of Zhongshan Hospital from January 2008 to December 2013 were retrospectively analyzed. Operative, postoperative conditions and long-term follow-up of these patients were evaluated.</p><p><b>RESULTS</b>Both the success rate and the complete resection rate were 100%. The average maximum diameter of the tumor was 1.5(range 0.6-4.5) cm. During the ESD process, two bleeding cases were treated successfully by endoscopic hemostasis. The average operation time was 40(10-80) min. The delayed hemorrhage developed in 2 cases within 1-3 days after operation, and were also treated successfully by endoscopic hemostasis. There was no perforation or delayed perforation. No emergency surgery was required for the complication. Twelve cases were diagnosed as mild-moderate dysplasia, 7 cases as high grade intraepithelial neoplasia, 16 cases as hyperplastic polyps, and 1 case as signet ring cell carcinoma with T1 stage, who underwent operation for resecting gastric stump and lymph node dissection 7 days after ESD without subsequent follow-up. The curative resection rate was 92.7%(35/36). The median follow-up of the remaining 35 patients was 36(6-78) months without discomfort and recurrence under gastroscopy.</p><p><b>CONCLUSION</b>ESD is safe and effective for EGC and precancerous lesions in the remnant stomach.</p>