Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Effect of jianpi jiedu recipe on microvessel density and cyclooxygenase-2 expression in Heliobacter pylori induced gastric cancer / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the regulatory effect of jianpi jiedu Recipe (JJR) on the microvessel density (MVD) and cyclooxygenase-2 (COX-2) in long-term infection of Helicobacter pylori induced gastric cancer of C57BL/6 mice, thus providing experimental bases for its treatment of the H. pylori correlated gastropathy.</p><p><b>METHODS</b>C57BL/6 mouse gastric cancer model induced by H. pylori infection was established by gastrogavage of H. pylori standard strain SS1. Mice were divided into the control group, the model group, low dose JJR group, and the high dose JJR group, 40 in each group. Mice were sacrificed after 72-week medication. Changes of the gastric mucosa MVD of mice in each group were detected by immunohistochemical method. Expressions of COX-2 mRNA and protein were detected by Real-time fluorescent quantitative polymerase chain reaction and immunohistochemical method.</p><p><b>RESULTS</b>The occurrence rate of gastric cancer in the control group, the model group, the low dose JJR group, and the high dose JJR group was 0, 22.2%, 11.1%, and 10.0%, respectively. The gastric mucosa MVD (number/cm2) of mice in each group was 2.50 +/- 1.54, 18.56 +/- 2.62, 14.61 +/- 3.60, and 7.39 +/- 1.75, respectively. The gastric mucosa MVD in the model group increased more obviously than that in the control group (P < 0.01). The gastric mucosa MVD significantly decreased in the low dose JJR group and the high dose JJR group (P < 0.01). Expressions of COX-2 mRNA and protein in the model group increased more obviously than those in the control group (P < 0.01). Low dose JJR and high dose JJR could decrease their expressions in a dose dependent manner.</p><p><b>CONCLUSIONS</b>H. pylori infection could increase the gastric mucosa MVD of C57BL/6 mice and promote COX-2 expressions, which might play a promoting effect in the incidence of H. pylori induced gastric cancer. JJR could decrease the gastric mucosa MVD and inhibit COX-2 expressions, which might be one of its important mechanisms of preventing and treating gastric cancer.</p>

Jianpi jiedu recipe inhibited Helicobacter pylori-induced the expression of cyclooxygenase-2 via p38MAPK/ATF-2 signal transduction pathway in human gastric cancer cells / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Jianpi Jiedu Recipe (JJR) on the expression of cyclooxygenase (COX-2) in Helicobacter pylori (Hp) infected gastric cancer cell line MKN 45, and its regulatory mechanism of p38MAPK signal transduction.</p><p><b>METHODS</b>The expressions of COX-2 mRNA and protein in human gastric cancer cell line MKN 45 infected by Hp type strain NCTC 11637 and the regulatory effect of JJR containing serum were detected using Real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR) and Western blot. The effects of Hp on COX-2 mRNA and protein expressions in human gastric cancer cell line MKN 45 were observed using blocking p38MAPK signal transduction pathway by p38MAPK specific inhibitor SB203580. The effects of JJR on Hp-infection activated p38MAPK signal transduction pathway and its downstream activating transcription factor 2 (ATF-2) were observed.</p><p><b>RESULTS</b>COX-2 mRNA and protein expressions were obviously higher after human gastric cancer cell line MKN 45 were infected by Hp (P<0.01). After blocking p38MAPK signal transduction pathway, COX-2 mRNA and protein expressions in Hp-induced MKN 45 cell line were obviously down-regulated (P<0.01). JJR containing serum down-regulated Hp-induced COX-2 mRNA and protein expressions in MKN 45 cell line in a dose dependent manner. Besides, it could inhibit the activation of Hp-induced p38MAPK signal pathway. It also showed obvious inhibition on the activity of its downstream transcription factor ATF-2.</p><p><b>CONCLUSIONS</b>Hp infection induced COX-2 expressions of gastric cancer cells via p38MAPK signal transduction pathway. JJR inhibited Hp-induced the expression of COX-2 through regulating p38MAPK/ATF-2 signal transduction pathway, which may be one of its mechanisms in prevention and treatment of Hp-induced gastric cancer.</p>

HIF-1α expression and retinal cell apoptosis in rat retina ischemia-reperfusion injury / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:Investigating the expression of HIF-1α,apoptosis of retinal cells and the role of HIF-1α in apoptosis in rats' retinal ischemia-reperfusion injury.METHODS:The rat model of experimental retinal ischemia-reperfusion injury was established by increasing the intraocular pressure to 110mmHg(1kPa=7.5mmHg)in rat eyes.At different time points of post ischemia,the expression of HIF-1α of the retina was detected by immunohistochemicalstaining,and apoptosis of the retinal cell was detected by terminal deoxynudeotidyl transferase medialed deoxyuridine triphosphatebiotin nick end labeling(TUNEL).RESULTS:HIF-1α appeared in the cells of retinal ganglion layer and inner nuclear layer at 2 hours after ischemia.The expression reached to a peak,12 hours after retinal ischemia-reperfusion,then the expression was dedined.The apoptotiC Cells were mainly in inner nuclear layer and could be detected at the 12th, 24th and 48th hour after ischemia,the peak value was the group of 24th hour.CONCLUSION:Expression of HIF-1α in the rats' retina is greatly enhanced after ischemia-reperfusion,which may be involved in the retinal injury:the injury of retinal neurons Occurs partly in the form of apoptosis.The expression of HIF-1α may play an important role in cell apoptosis.

Study of Helicobacterpylori on p38MAPK signal transduction pathway activation in gastric epithelial cancer cells line MKN45 / 中国癌症杂志

Background and purpose:Cyclooxygenase-2 (Cyclooxygenase-2,COX-2) is an important rate-limiting enzyme that is responsible for transformation of arachidonic acid into prostaglandins(PGs).Although Helicobacter pylori(Hp) infection-induced gastric over-expression of COX-2 (COX-2) is an important factor of gastric cancer,the mechanism of COX-2 expression in gastric mucosa cells infected with Hp is still not clear.Our study was to reveal the effect of Hp on expression of COX-2(cyclooxygenase-2),the impact of p38MAPK signaling pathway in human gastric epithelial cancer cells line MKN45,and to investigate the potential mechanisms of expression of COX-2. Methods:The expression of COX-2 mRNA infection by standard Hp NCTC11637 in human gastric epithelial cancer cells line MKN45 was evaluated by real-time fluorogenic quantitative polymerase chain reaction (RFQ-PCR).The effect of infection by Hp on COX-2 expression,activation of p38MAPK and its downstream of the ATF-2 was assayed by Western blot.Results:The expression of COX-2 mRNA in MKN45 cells infected by Hp compared with control group,COX-2 mRNA had 3 fold,7.2 fold,5.1 fold,4.3 fold up-regulation after 3 hrs,6 hrs,9 hrs,12 hrs,respectively. COX-2 mRNA expression in each time group was significantly higher than that in the control group(P

The significance and expression of HIF-1α and COX-2 in the retinal neovascularization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression and significance of hypoxia-inducible factor -1α (HIF-1α)and Cyclooxygenase-2(COX-2) in the retinal neovascularization.METHODS: Mouse model of hyperoxia-induced ischemic retinopathy were established. A novel flucorescein-dextran perfusion method has been developed to assess the vascular pattern. histological methods were used to count blood vessel profiles in the inner retina with HE staining.HIF-1α and COX-2 expression in the retina was determined by immunohistochemical method.RESULTS: Lots of neovascularization were seen in hyperoxia group. The number of nuclei of proliferative retinal vessels increased significantly as compared with normal control group (P＜0.001). The expression of HIF -1α was noted in the ganglion cells and retinal blood vessels. The expression of COX-2 was noted in the inner nuclear layer and ganglion cells and retinal blood vessels.CONCLUSION: There are the expression of HIF-1α and COX-2 in the retinal neovascularization and they have correlation.

Clinical experience of simultaneous aortic operation and coronary artery bypass grafting / 中华外科杂志

<p><b>OBJECTIVE</b>To summarized the experience of simultaneous aortic operation and coronary artery bypass.</p><p><b>METHODS</b>Between November 1997 and September 2004, thirty-six patients who underwent combined aortic operation and coronary artery bypass graft (CABG) were reviewed with a mean age of (57 +/- 12) years (range 31 to 75). Nineteen patients were suffered from aortic dissection. There were 17 patients of aortic aneurysm, 5 aortic root aneurysm, 5 ascending aortic aneurysm, 4 aortic arch aneurysm, 3 abdominal aneurysm. Preoperational coronary angiography was performed in 1 of 10 acute type A dissection patients. The coronary arteries were involved by dissection in 7 acute type A dissection patients. The artherosclerosis of coronary artery was found during operation in 2 patients. Among 7 patients with chronic type A aortic dissection, coronary angiography was performed in 2, coronary artery was involved by dissection in 2 and coronary arterosclaerosis was founded in 3. There were 2 patients with acute or chronic type B aortic dissection. The stenosis of coronary artery was confirmed by preoperative angiography in the patients with aortic aneurysm. There were 57 coronary bypass grafts, 6 of them were artery grafts, and others were venous grafts.</p><p><b>RESULTS</b>The mean cardiopulmonary bypass time was (157 +/- 54) min, and the mean aortic cross clamp time was (98 +/- 31) min. Five patients with type A aortic dissection died postoperatively, 3 from heart failure leading to multi organ system failure, 1 from cerebral hernia and one from ischemia of intestinal tract. Postoperative complication included reoperation for hemorrhage in 1 patient, respiratory failure in 1 patient.</p><p><b>CONCLUSIONS</b>Type A aortic dissection with coronary involvement or arterosclaerosis is associated with high mortality rate. Coronary artery angiography should be performed in the elder than 50 years patient with aortic aneurysm. Combined aortic aneurysm operation and CABG is a safe procedure.</p>

The application of modified classification of the aortic dissection / 中华外科杂志

<p><b>OBJECTIVE</b>To determine the indication, optimal operative procedures, plan and the estimation of the prognosis depending on the subtype of aortic dissection defined by the extension and extent of dissection.</p><p><b>METHODS</b>The outcome of 708 patients with aortic dissection between January 1994 and December 2004 was analyzed. Among them 477 patients suffered from Stanford type A aortic dissection were treated. Type A dissection can be classified into 3 subtypes based on the pathological change of the aortic root. Type A1 (No pathological change type): 212 patients underwent ascending aorta replacements; Type A2 (mild pathological change type): 63 patients underwent ascending aortic replacement with concomitant aortic valve and valsalva sinus plasty and David procedure was performed in 9 patients; Type A3 (severe pathological change type): 193 patients underwent Bentall procedure. The method of aortic arch repair was determined by the pathological type of distal aorta. Total aortic arch replacement was performed in 78 patients with complex type (type C). There hundred and ninety-nine patients with simple type (type S) underwent partial aortic arch replacement. 231 patients suffered from Stanford type B aortic dissection. Type B dissection can be classified into 3 subtypes based on dilated extension of proximal descending aorta. Type B1 (no dilation was confined in the proximal of thoracic descending aorta): endoluminal stent graft repair was performed in 103 patients. Replacement of the partial proximal thoracic descending aorta and replacement combined with stented elephant trunk procedure were performed in 32 and 12 patients respectively; Type B2 (aneurysm in thoracic descending aorta): 32 patients underwent the part proximal thoracic descending aorta replacement combined with aorta plasty. 21 patients underwent the replacement of entire thoracic descending aorta; Type B3 (aneurysm in thoracic descending and abdominal aorta): thoracoabdominal aortic replacement was operated in 31 patients with deep hypothermia circulatory arrest; Type BC (complex type): 44 patients were performed the operation with the use of deep hypothermia circulatory arrest because their left subclavian arteries or distal aortic arch were affected by the dissection; Type BS (simple type): 103 patients were underwent endoluminal stent graft repair. In the 60 patients, the operations were performed by using the technique which preserved blood was transfused back by pump via the femoral artery. Femoro-femoral bypass was performed in 24 patients.</p><p><b>RESULTS</b>Type A: the operative mortality was 4.6% (27/477), and the hospital morbidity was 14.5% (69/477). Type B: the hospital mortality of endoluminal stent graft repair was 1.9% (2/103). 9.7% (10/103) had mild leakage from proximal communications. The morbidity was 2.9% (3/103) in stent group. The mortality was 3.1% (4/128), and the hospital morbidity was 18.8% (24/128) in the operative group.</p><p><b>CONCLUSION</b>The subtype of aortic dissection is much useful in determining the optimal procedure, operative indication and plan, estimating the prognosis.</p>