miR-375 Attenuates The Migration and Invasion of Osteosarcoma Cells by Targeting MMP13 / 生物化学与生物物理进展

ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.

Clinical characteristics of newly diagnosed acute myeloid leukemia patients with NPM1 mutation / 中国实验血液学杂志

The purpose of this study was to investigate the clinical characteristics of newly diagnosed acute myeloid leukemia (AML) patients with NPM1 mutation in exon 12 and to explore the relationship between NPM1 mutation and FLT3-ITD, IDH1 mutation. The AML clinical data and bone marrow samples of patients were collected. The diagnosis and classification were based on WHO criteria. The genomic DNA was extracted and NPM1 mutation was detected by sequencing after PCR. The specimens of 389 AML patients were tested. The results showed that the NPM1 mutation was found in 14.1% samples (55/389). The incidence of FLT3-ITD mutation was 14.7% (57/389) . The incidence of IDH1 mutation was 6.4% (25/389) . NPM1 mutation was not detected in AML with AML1-ETO, PML-RARA or CBF-MYH11 fusion genes. The incidences of FLT3-ITD and IDH1 mutation were 29.1% and 12.7% respectively in AML with NPM1 mutation. The incidences of FLT3-ITD and IDH1 mutation were 12.3% and 5.4% respectively in AML without NPM1 mutation. The incidences of FLT3-ITD and IDH1 mutation were significantly higher in AML with NPM1 mutation than that in AML without NPM1 mutation. The incidence of NPM1 mutation in normal karyotype AML was 26.5% (35/132) which significantly higher than that in other AML. The AML with NPM1 mutation characterized by older age, high platelet number, higher incidence in AML-M5, lower CD34 positive cells, more possible co-existence with FLT3-ITD and IDH1 mutation and other clinical features. The complete remission rate after one cycle of induction chemotherapy was 69.8% in AML without NPM1 mutation. The complete remission rate after one cycle of induction chemotherapy was 72.2% in AML with NPM1 mutation, there was no significant difference between them (P = 0.07). It is concluded that AML with NPM1 mutation has distinct clinical features. NPM1 mutation can co-exists with FLT3-ITD and IDH1 mutation, but not with AML1-ETO, PML-RARA or CBF-MYH11 fusion genes.

Curative effect of BCG-polysaccharide nuceic acid on atopic dermatitis in mice

OBJECTIVE@#To explore the effect of bacilli Galmette-Gurin (BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism.@*METHOD@#Forty NC/Nga mice were selected and randomly divided into Group A (model group), Group B (dexamethasone treatment group), Group C (BCG polysaccharide nucleic acid treatment group) and Group D (control group) with 10 mice in each group. Atopic dermatitis model were constructed by applying 2, 4-dinitrochlorobenzene on the skin of the mice. Mice in Group D were treated with acetone solution (100 μL) on the foot pad and abdomen after hair removal at the age of 7 weeks, then on ear skin at the age of 8-13 weeks. For mice in A, B and C groups, 100 μL of acetone solution containing 2, 4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks, then on ear skins at the age of 8 to 13 weeks. At the age of 7-13 weeks, mice in Group A and Group D were treated with 100 μL saline (i.p.); mice were given dexamethasone (0.1 mL/kg, i.p.) every other day for 7 weeks in Group B; mice were treated with BCG polysaccharide nucleic acid (0.5 mg/kg, i.p.) every other day for 7 weeks in Group C. The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week. The mice were sacrificed after the last administration of drugs. IgE, IL-4, IL-10, IL-12 and IFN-γ in the plasma were detected using ELISA, and RT-PCR method was employed to detect the concentrations of IL-4, IL-10, IL-12 and IFN-γ proteins. After HE staining, the lesion degree of inflammation in ear tissue was observed microscopically.@*RESULTS@#The ear thickness and scratching frequency of Group A were significantly higher than those in group B, C and D (P0.05); the concentrations of IgE, IL-4 and IL-10 in the plasma and the expression of IL-4, IL-10 mRNA in the spleen tissues of Group A, B and C were all significantly higher than those of Group D (P<0.05); the concentrations of plasma IL-12 and IFN-γ, and spleen protein expression of IL-12 and IFN-γ in Group C mice were significantly higher than those of Group A (P<0.05). Histological observation showed obvious ear tissue exudation, erythema, swelling, desquamation of skin, and scabbing in Group A. Histopathology of the skin lesion also showed hyperkeratosis, focal-parakeratosis, stratum spinosum hypertrophy, mild sponge-like edema, a large number of lymphocytes along with plasma cell infiltration in dermis, angiectasis and hyperemia in Group A, while degree of ear skin lesion in Group B and D mice was significantly lighter than that of Group A.@*CONCLUSIONS@#BCG polysaccharide nucleic acid can significantly reduce the serum IgE concentrations, increase the expression of IL-12, IFN-γ protein, correct the imbalance of Thl/Th2 in atopic dermatitis mice, and has obvious inhibitory effect on atopic dermatitis in NC/Nga mice.

Curative effect of BCG-polysaccharide nuceic acid on atopic dermatitis in mice

Objective: To explore the effect of bacilli Galmette-Gurin (BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism. Method: Forty NC/Nga mice were selected and randomly divided into Group A (model group), Group B (dexamethasone treatment group), Group C (BCG polysaccharide nucleic acid treatment group) and Group D (control group) with 10 mice in each group. Atopic dermatitis model were constructed by applying 2, 4-dinitrochlorobenzene on the skin of the mice. Mice in Group D were treated with acetone solution (100 μL) on the foot pad and abdomen after hair removal at the age of 7 weeks, then on ear skin at the age of 8-13 weeks. For mice in A, B and C groups, 100 μL of acetone solution containing 2, 4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks, then on ear skins at the age of 8 to 13 weeks. At the age of 7-13 weeks, mice in Group A and Group D were treated with 100 μL saline (. i.p.); mice were given dexamethasone (0.1 mL/kg, i.p.) every other day for 7 weeks in Group B; mice were treated with BCG polysaccharide nucleic acid (0.5 mg/kg, i.p.) every other day for 7 weeks in Group C. The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week. The mice were sacrificed after the last administration of drugs. IgE, IL-4, IL-10, IL-12 and IFN-γ in the plasma were detected using ELISA, and RT-PCR method was employed to detect the concentrations of IL-4, IL-10, IL-12 and IFN-γ proteins. After HE staining, the lesion degree of inflammation in ear tissue was observed microscopically. Results: The ear thickness and scratching frequency of Group A were significantly higher than those in group B, C and D (. P0.05); the concentrations of IgE, IL-4 and IL-10 in the plasma and the expression of IL-4, IL-10 mRNA in the spleen tissues of Group A, B and C were all significantly higher than those of Group D (. P<0.05); the concentrations of plasma IL-12 and IFN-γ, and spleen protein expression of IL-12 and IFN-γ in Group C mice were significantly higher than those of Group A (. P<0.05). Histological observation showed obvious ear tissue exudation, erythema, swelling, desquamation of skin, and scabbing in Group A. Histopathology of the skin lesion also showed hyperkeratosis, focal-parakeratosis, stratum spinosum hypertrophy, mild sponge-like edema, a large number of lymphocytes along with plasma cell infiltration in dermis, angiectasis and hyperemia in Group A, while degree of ear skin lesion in Group B and D mice was significantly lighter than that of Group A. Conclusions: BCG polysaccharide nucleic acid can significantly reduce the serum IgE concentrations, increase the expression of IL-12, IFN-γ protein, correct the imbalance of Thl/Th2 in atopic dermatitis mice, and has obvious inhibitory effect on atopic dermatitis in NC/Nga mice.

Narrow band imaging versus iodine staining for margin determination of early esophageal cancer during endoscopic submucosal dissection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the clinical value of narrow band imaging (NBI) and iodine staining for margin determination of early esophageal cancer during endoscopic submucosal dissection (ESD).</p><p><b>METHODS</b>Clinical data of 87 patients with early esophageal cancers undergoing endoscopic submucosal dissection (ESD) were analyzed retrospectively. Patients were assigned to NBI group and iodine staining group according to the staining method before ESD operation. Clinicopathological features, esophageal spasm ratio, operation time, en bloc resection rate, complications, local recurrence, and distant metastases were compared between the two groups.</p><p><b>RESULTS</b>There were 37 patients in NBI group while 50 patients in iodine staining group. Location and size of the lesions between two groups were not significantly different. The ratio of moderate-severe esophageal spasm in NBI group was significantly lower as compared to iodine staining group [10.8%(4/37) vs. 32.0%(16/50), P<0.05]. The average operation time in NBI group was significantly shorter than that in iodine staining group [(42.2±19.5) min vs. (53.3±30.9) min, P<0.05). All the tumors were resected in an en bloc fashion and the R0 resection rate was 100%. Perforations in 2 patients and delayed bleeding in 1 patient were successfully treated by endoscopic methods. Esophageal strictures occurred in 3 patients of NBI group and 4 patients of iodine staining group, who were treated by endoscopic dilation and retrievable stents. During mean 13.2 months (range 4 to 20 months) follow-up periods, local recurrence occurred in 2 patients of NBI group and 2 patients of iodine staining group. These patients received ESD or other surgery.</p><p><b>CONCLUSION</b>Compared with iodine staining, using NBI for margin determination of early esophageal cancer during ESD is more convenient and fast because of distinctly lower degree of esophageal spasm.</p>

Application and evaluation of the new technique of minimal endoscopic dissection for gastrointestinal tract submucosal tumor / 中华胃肠外科杂志

Submucosal tumors (SMTs) are occasionally found in the gastrointestinal tract during endoscopy. Endoscopic ultrasonography(EUS) can not reliably distinguish benign from malignant SMTs, because the exact histopathologic features of the lesion can not be defined. With the introduction of endoscopic submucosal dissection(ESD), gastrointestinal SMTs can be diagnosed and resected endoscopically. The purpose of this article is to elucidate the indication, method and efficacy of endoscopic resection of gastrointestinal SMTs.

Therapeutic value of endoscopic submucosal dissection for gastrointestinal stromal tumor in the esophagogastric junction / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of endoscopic submucosal dissection (ESD) for gastrointestinal stromal tumor(GIST) in the esophagogastric junction(EGJ).</p><p><b>METHODS</b>Twenty patients with pathologically confirmed GIST in the EGJ were screened from all the patients undergoing ESD between November 2007 and June 2011. The clinicopathological and postoperative follow up data were analyzed.</p><p><b>RESULTS</b>There were 11 males and 9 females with the age ranging from 29 to 67 years(mean, 54.1 years). The maximum diameter of the lesions ranged from 8 to 20 mm(mean,14.8 mm). Fifteen patients underwent endoscopic submucosal excavation, 4 patients underwent endoscopic full-thickness resection, and 1 patient underwent submucosal tunneling endoscopic resection. The operative time ranged from 15 to 90 min(mean, 47.8 minutes). The estimated blood loss was 5 to 200 ml. The en bloc resection rate was 100%. Perforations occurred in 4 patients, pneumoperitoneum in 3 patients, cardia mucosal tear in 1 patient. All the complications were successfully managed with endoscopic intervention and conservative therapy. The post-operative follow up ranged from 3 to 36 months(mean, 13.2 months). No local recurrence or distant metastasis occurred.</p><p><b>CONCLUSION</b>ESD is a safe and effective procedure for GIST in the EGJ.</p>

Selection and evaluation of endoscopic resection for submucosal tumors of the esophagogastric junction originating from muscularis propria / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical application and indication of endoscopic dissection technique for submucosal tumors (SMTs) of the esophagogastric junction (EGJ) originating from the muscularis propria.</p><p><b>METHODS</b>A total of 143 SMTs of the EGJ were treated by endoscopic resection in the Endoscopy Center of Zhongshan Hospital Affiliated to Fudan University between March 2007 and June 2011. The clinical and histopathologic feature, surgical approach, en bloc resection rate, complications, and postoperative follow up were evaluated.</p><p><b>RESULTS</b>There were 74 males and 69 females with a mean age of 49.1 years old. The en bloc resection rate was 94.4%(135/143). There were 126 patients who underwent endoscopic submucosal excavation in an en bloc fashion. Six patients underwent endoscopic full-thickness resection without laparoscopic assistance. Three patients underwent submucosal tunneling endoscopic resection. The other 8 SMTs were partially resected for histological evaluation and the residual tumors were further treated with nylon snare ligation. The mean lesion size was 17.6 mm. The mean procedure time was 45.1 minutes and the mean intraoperative bleeding was 50.0 ml. Perforations occurred in 6 patients and metal clips were used to close the defect. One patient with Mallory-Weiss syndrome was successfully treated with conservative treatment. Pathological examination showed that the lesions were leiomyoma (n=121), gastrointestinal stromal tumor (n=20), granulosa cell tumor (n=1), and intermuscular lipoma (n=1). No local recurrence and distant metastasis were noted during the follow-up (range, 3-48 months).</p><p><b>CONCLUSION</b>Endoscopic resection technique is safe and effective, and should be selected for each patient individually.</p>

Application and evaluation of submucosal tunneling endoscopic resection of gastric submucosal tumors originating from the muscularis propria layer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical value of submucosal tunneling endoscopic resection(STER) for gastric submucosal tumor(SMT) originating from the muscularis propria (MP) layer.</p><p><b>METHODS</b>Clinicopathological data of 23 cases with gastric SMT originating from the MP layer treated with STER from September 2010 to December 2011 were analyzed retrospectively.</p><p><b>RESULTS</b>There were 13 males and 10 females. The age ranged from 28 to 73(mean, 52.4) years old. Of the 23 SMTs, 11 were located in the cardia adjacent to the gastric body, 4 in the cardia adjacent to the fundus, 5 in the lesser curvature of gastric body and 3 in the gastric antrum of greater curvature. All the SMTs originating from the MP layer, 14 were located in the superficial MP layer and 9 in the deep MP layer(including 5 gastric SMTs close to serosa). En bloc STER was performed successfully in all the patients. The mean lesion size was 2.1 cm(range 1.5-3.2 cm). The mean procedure time was 54.8 min(range 30-125 min). Pathological examination showed that the lesions were leiomyomas(n=10), stromal tumors(n=8), glomus tumor(n=2), Schwannoma(n=2), and calcifying fibrous tumor(n=1). Both lateral and vertical margins were negative in all the cases. Three patients developed pneumothorax and subcutaneous emphysema and 5 pneumoperitoneum. One patient developed effusion under the left half of the diaphragm and secondary infection. All of them recovered uneventfully after conservative treatments. No delayed bleeding or GI tract leakage was noticed. None of the 23 cases encountered submucosal hematoma or infection. No tumor residual or recurrence was found during the follow up(range, 3-18 months).</p><p><b>CONCLUSIONS</b>STER is a safe, effective for appropriate lesions in the MP layer of the stomach. En bloc resection and accurate histopathological evaluations can be achieved.</p>

Clinical value of different magnifying chromoendoscopy methods in screening gastric precancerous lesions and early cancers / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To prospectively evaluate the clinical value of different magnifying chromoendoscopy(MCE) methods in screening gastric precancerous lesions and early cancers.</p><p><b>METHODS</b>Between March 2010 and October 2011, among all the patients aged over 40 who received esophagogastroduodenoscopy at Zhongshan hospital, Fudan University, suspicious lesion was detected in 699 patients, who were randomly assigned to three groups: epinephrine dye(n=240), indigo carmine dye(n=246), and acetic acid-indigo carmine mixture dye(n=213). Diagnosis was made according to surface patterns and microvessels of the lesion. Pathological diagnosis was used as the gold standard. The concordance between endoscopic diagnosis and pathological diagnosis was evaluated through the agreement(Kappa) test. McNemar Paired chi-square test was used to compare the concordance of three MCE methods, regular white light, magnification alone, and NBI magnifier before and after MCE.</p><p><b>RESULTS</b>Pathological examination showed inflammatory lesions in 415 patients, intestinal metaplasia in 190, low grade intra-epithelial neoplasia in 17, and high grade intra-epithelial neoplasia or early cancer in 77. The percentage of patients with consistent endoscopic and pathological diagnosis was 77.1%(185/240) for epinephrine dye, 80.5%(198/246) for indigo carmine dye, and 81.2%(173/213) for acetic acid-indigo carmine mixture dye. Kappa values were 0.579, 0.502, and 0.667 respectively(all P<0.01). For the screening of high grade intra-epithelial neoplasia or early cancer, the diagnostic sensitivities were 84.0%, 83.3%, and 92.9%, respectively, and the specificities were 98.6%, 97.3%, and 98.4%. All the three chromoendoscopy methods improved the diagnostic accuracy for precancerous lesions compared with conventional gastroscopic observation with white light(all P<0.01). Indigo carmine and acid-indigo carmine mixture dye improved the diagnostic accuracy of magnification alone(both P<0.05). There was no significant difference in diagnostic accuracy between each MCE method and magnifying NBI observation(all P>0.05).</p><p><b>CONCLUSION</b>NBI magnification and all the three MCE methods may improve the diagnostic accuracy of early gastric cancer and precancerous lesions.</p>

Endoscopic management of early postoperative anastomotic hemorrhage / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>The study aimed to evaluate the efficacy of endoscopic therapy for early postoperative anastomotic hemorrhage.</p><p><b>METHODS</b>Fourteen patients experienced an episode of early postoperative anastomotic hemorrhage and were treated endoscopically from January 2005 to June 2010. The clinical data was analyzed retrospectively.</p><p><b>RESULTS</b>Fourteen patients(9 males and 5 females, median age 57.5 years, range 26-74 years) were diagnosed with postoperative hemorrhage between 6 hours to 14 days after surgery. The blood loss ranged from 500 to 1500 ml. Sclerosing agent injection, electrocoagulation, and hemoclips were attempted to control the bleeding. Endoscopic approach to control early postoperative anastomotic hemorrhage was successful in all the patients. No recurrent bleeding was observed during the follow-up. No complications associated with endoscopic therapy.</p><p><b>CONCLUSION</b>Endoscopic approach for the management of early postoperative anastomotic hemorrhage is feasible with high success rate and associated with no complications.</p>

Long-term efficacy of endoscopic excision of rectal carcinoids / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the long-term efficacy of endoscopic excision for rectal carcinoids.</p><p><b>METHODS</b>Clinical data of 91 patients with rectal carcinoids treated by endoscopic excision from 2000 to 2007 were analyzed retrospectively.</p><p><b>RESULTS</b>The average size of the primary tumor was 0.8 cm(range 0.3 to 2.3 cm). All the tumors were localized within the submucosal layer showing typical histology without lymphatic or vessel infiltration. Follow-up was available for 80 patients with mean 32.5 months (range 6 to 96 months). There was no recurrence in 65 patients with tumor size < 1.0 cm. Recurrence occurred in 3 cases among 25 patients with tumor size from 1.0 to 2.0 cm, and 1 died of hepatic metastasis. The 1-, 3-, and 5-year survival rates of the patients were 100%, 98.0%, and 91.4% respectively.</p><p><b>CONCLUSIONS</b>Tumor size and depth of invasion are two important prognostic factors of rectal carcinoids. Endoscopic excision is useful for rectal carcinoid patients with tumor size < 1.0 cm and located within the submucosal layer.</p>

Diagnosis and treatment of gastrointestinal lipoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To summarize the experience of diagnosis and treatment of gastrointestinal lipoma.</p><p><b>METHODS</b>The clinical data of 34 patients with gastrointestinal (GI) lipoma from 1993 to 2007 were analyzed retrospectively.</p><p><b>RESULTS</b>GI lipoma produced a variety of symptoms including gastrointestinal bleeding, abdominal pain, anemia, intussusception, and bowel obstruction. The diagnostic accuracy of endoscopic ultrasonography(EUS) for GI lipoma was 93.8%. Twelve GI lipomas were resected under endoscopy, the remainder at laparotomy, partial resection, gastrectomy or enterectomy being performed. Twenty-eight cases were followed up from 1 month to 168 months. No recurrence and metastasis were observed except one case dying of gastric liposarcoma.</p><p><b>CONCLUSIONS</b>EUS is an effective method for diagnosing GI lipomas. The treatment of GI lipomas is surgical resection, and endoscopic removal of GI lipomas is safe following the guidance of the present therapeutic strategy.</p>

Clinical value of percutaneous endoscopic gastrostomy and jejunostomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and safety of percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic jejunostomy(PEJ).</p><p><b>METHODS</b>From June 1996 to April 2005, clinical data of 121 patients treated with PEG or PEJ were analyzed retrospectively.</p><p><b>RESULTS</b>A total of 121 patients experienced 134 times of PEG or PEG plus PEJ, including 90 cases (103 times) treated with PEG and 31 patients treated with PEG plus PEJ. Thirteen patients treated with PEG had fistula replacement 6-10 months after PEG. All patients had quick nutrition recovery after fistula tube insert,therefore parenteral nutrition was not required. No severe complications occurred in all patients after 10 months of following-up. Four patients had subcutaneous infection around fistula 4-10 days after PEG.</p><p><b>CONCLUSION</b>PEG and PEJ are safe and new methods for gastrointestinal decompression and enteral nutrition, which can be substitutes for nasogastric tube.</p>