Research on the anti-tumor effect of nordihydroguaiaretic acid targeting MyD88 / 药学学报

This study mainly explores the role of myeloid differentiation primary response protein 88 (MyD88) in tumorigenesis and development, to identify active compounds targeting MyD88. CRISPR/Cas9 system and xenograft tumor model were used to detect the effect of MyD88 deletion on tumor growth, and the experimental animal ethics review number was PZSHUTCM200828006. Microscale thermophoresis technology (MST) was used to identify compounds directly bind to MyD88 and further detect the impact of candidate small molecules on cell proliferation. Results showed that depletion of MyD88 significantly inhibited xenograft tumor growth of colon cancer, pancreatic cancer and skin cancer and the activity of NF-κB signaling pathway. MST showed that nordihydroguaiaretic acid (NDGA) bound to MyD88, with the binding dissociation constant Kd of 14.61 µmol·L-1. NDGA inhibited NF-κB reporting system activation and phosphorylation of p65, the key factor in NF-κB signal pathway. In addition, the results of colony formation assay showed that NDGA suppressed the proliferation of tumor cells. The above results show that, MyD88 is a potential therapeutic target for colon cancer, pancreatic cancer and skin cancer, NDGA directly binds to MyD88 and inhibits the activity of NF-κB signaling pathway, as well as inhibits the proliferation of pancreatic cancer, skin cancer and colon cancer cells.

Influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome: A retrospective study / 中华血液学杂志

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.

Cinobufagin disrupts mitosis and microtubule polymerization via targeting KATNB1 in cancer cells / 药学学报

Huachansu is a traditional Chinese medicine widely used in the clinic for cancer therapy, while the underlying mechanism is not fully clarified. This study was to investigate the targets and mechanisms of cinobufagin (CBG), an active component of Huachansu, in terms of blocking mitosis of cancer cells. Propidium iodide (PI) DNA staining was used to analyze the effect of CBG on cell cycle. The effect of CBG on mitosis of cancer cells was examined by α-tubulin and pericentrin staining after synchronization by a double thymidine block. Tubulin turbidity, tubulin polymerization and α‍-tubulin immunofluorescence assays were used to evaluate the effect of CBG on microtubule polymerization. CRISPR/Cas9 gene-editing technology was used to knockout microtubule-severing protein Katanin regulatory subunit B1 (KATNB1) in HCT116 cells, and the inhibitory effect of CBG on wild-type cells and knockout cells was measured by CCK-8. The engagement of CBG with KATNB1 was measured by CETSA and DARTS assays. The effect of CBG on KATNB1 protein and mRNA level was examined by Western blot and real-time PCR, respectively. Our data showed that CBG arrested HCT116 cell cycle at the G2/M phase, disrupted mitosis and induced centriole overduplication. CBG significantly inhibited tubulin polymerization in vitro and in vivo. The cytotoxicity of CBG inhibition on HCT116 was significantly attenuated upon KATNB1 depletion. Moreover, CBG bound to KATNB1 and decreased its protein level, while mutated KATNB1 weakened this effect. In conclusion, CBG inhibited microtubule polymerization via targeting KATNB1, thereby disrupting mitosis in cancer cells.

Circ_0049447 acts as a tumor suppressor in gastric cancer through reducing proliferation, migration, invasion, and epithelial-mesenchymal transition / 中华医学杂志(英文版)

BACKGROUND@#Although increasing abnormal expression of circular RNAs (circRNAs) has been revealed in various cancers, there were a small number of studies about circRNAs in gastric cancer (GC). Here, we explored the expression and function of a novel circRNA, circ_0049447, in GC.@*METHODS@#A total of 80 GC tissues and non-tumorous tissues were collected from the First Affiliated Hospital of China Medical University. And all cells were cultured with 10% fetal bovine serum and incubated at 37°C and 5% CO2. The expression of circ_0049447 was quantified by real-time polymerase chain reaction. The biological function of circ_0049447 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated by cell counting kit-8 (CCK-8), colony formation assay, transwell migration and invasion assay, and Western blotting. Luciferase report assay was used to verify the direct binding between circ_0049447 and predicted microRNA (miRNA). Furthermore, a xenograft mouse model was used to validate the function of circ_0049447 in vivo.@*RESULTS@#We demonstrated that circ_0049447 was downregulated in GC (P < 0.001). The area under the receiver operating characteristic curve reached 0.838, while sensitivity was 82.3% and specificity was 77.2%. CCK-8 and colony formation assay showed that overexpression of circ_0049447 could inhibit the proliferation (P < 0.05). Transwell migration and invasion assay showed upregulated circ_0049447 could impede migration in GC cells (P < 0.05). In addition, overexpression of circ_0049447 could impede GC cell EMT. Upregulation of miR-324-5p in GC specimens and direct binding between miR-324-5p with circ_0049447 proven by luciferase reporter assay indicated that circ_0049447 may inhibit GC by sponging certain miRNA.@*CONCLUSION@#Circ_0049447 acts as a tumor suppressor in GC through reducing proliferation, migration, invasion, and EMT, and it is a promising biomarker for diagnosis.

Investigation on population dynamics and Echinococcus infections in small rodents around human settlement in Yushu City, Qinghai Province / 中国血吸虫病防治杂志

Objective To investigate the population dynamics and Echinococcus infections in small rodents around human settlement in Yushu City, Qinghai Province. Methods Rodents were captured using the mouse trap method in pastures from Batang Township and Longbao Township of Yushu City, Qinghai Province on May, August and October, 2018. The body weight and snout-vent length of all captured rodents were measured, and the species was identified according to the rodent morphology. Genomic DNA was extracted from rodent liver specimens and lesion specimens, and the mitochondrial cox1 gene of Echinococcus was amplified using PCR assay for identification of parasite species. In addition, the tissue specimens positive for PCR assay were sampled for pathological examinations. The prevalence of Echinococcus infections was estimated in rodents, and a phylogenetic tree was created based on Echinococcus cox1 gene sequences. Results A total of 285 small rodents were captured, including 143 Ochotona curzoniae (50.2%), 141 Lasiopodomys fuscus (49.5%), and 1 Neodon irene (0.3%), and there was a remarkable variation in habitat selection among these three rodent species. The number of L. fuscus correlated positively with vegetation coverage (r = 0.350, P = 0.264), with the greatest number seen in August, and the number of O. curzoniae negatively with vegetation coverage (r = −0.371, P = 0.235), with the highest number seen in August and the lowest number in May. The female/male ratios of O. curzoniae and voles were 1:0.96 and 0.82:1, respectively. The body weight (r = 0.519, P < 0.01) and snout-vent length (r = 0.578, P < 0.01) of O. curzoniae showed a tendency towards a rise with month, while the body weight (r = −0.401, P < 0.01) and snout-vent length (r = −0.570, P < 0.01) of voles presented a tendency towards a reduction with month. No Echinococcus infection was detected in voles, while 2.1% prevalence of E. shiquicus infection was seen in O. curzoniae. Phylogenetic analysis revealed consistent sequences of cox1 gene from E. shiquicus in Yushu City of Qinghai Province and Shiqu County, Ganzi Tibetan Autonomous Prefecture of Sichuan Province. Conclusions The small rodents around the human settlement in Yushu City of Qinghai Province mainly include O. curzoniae and L. fuscus, with the greatest numbers seen in May and August, respectively. Following the concerted efforts for echinococcosis control, the prevalence of Echinococcus infections is low in small rodents around the human settlement in Yushu City; however, there is still a risk of echinococcosis transmission.

Differences in symptoms and pre-hospital delay among acute myocardial infarction patients according to ST-segment elevation on electrocardiogram: an analysis of China Acute Myocardial Infarction (CAMI) registry / 中华医学杂志(英文版)

BACKGROUND@#Approximately 70% patients with acute myocardial infarction (AMI) presented without ST-segment elevation on electrocardiogram. Patients with non-ST segment elevation myocardial infarction (NSTEMI) often presented with atypical symptoms, which may be related to pre-hospital delay and increased risk of mortality. However, up to date few studies reported detailed symptomatology of NSTEMI, particularly among Asian patients. The objective of this study was to describe and compare symptoms and presenting characteristics of NSTEMI vs. STEMI patients.@*METHODS@#We enrolled 21,994 patients diagnosed with AMI from China Acute Myocardial Infarction (CAMI) Registry between January 2013 and September 2014. Patients were divided into 2 groups according to ST-segment elevation: ST-segment elevation (STEMI) group and NSTEMI group. We extracted data on patients' characteristics and detailed symptomatology and compared these variables between two groups.@*RESULTS@#Compared with patients with STEMI (N = 16,315), those with NSTEMI (N = 5679) were older, more often females and more often have comorbidities. Patients with NSTEMI were less likely to present with persistent chest pain (54.3% vs. 71.4%), diaphoresis (48.6% vs. 70.0%), radiation pain (26.4% vs. 33.8%), and more likely to have chest distress (42.4% vs. 38.3%) than STEMI patients (all P < 0.0001). Patients with NSTEMI were also had longer time to hospital. In multivariable analysis, NSTEMI was independent predictor of presentation without chest pain (odds ratio: 1.974, 95% confidence interval: 1.849-2.107).@*CONCLUSIONS@#Patients with NSTEMI were more likely to present with chest distress and pre-hospital patient delay compared with patients with STEMI. It is necessary for both clinicians and patients to learn more about atypical symptoms of NSTEMI in order to rapidly recognize myocardial infarction.@*TRIAL REGISTRATION@#www.clinicaltrials.gov (No. NCT01874691).

Angiographic characteristics and in-hospital mortality among patients with ST-segment elevation myocardial infarction presenting without typical chest pain: an analysis of China Acute Myocardial Infarction registry / 中华医学杂志(英文版)

Background@#Patients with ST-segment elevation myocardial infarction (STEMI) who present without typical chest pain are associated with a poor outcome. However, whether angiographic characteristics are related to a higher risk of mortality in this population is unclear. This study aimed to investigate whether the higher mortality risk in patients with STEMI without chest pain could be explained by their "high-risk" angiographic characteristics.@*Methods@#We used data of 12,145 patients with STEMI who was registered in China Acute Myocardial Infarction registry from January 2013 to September 2014. We compared the infarct-related artery (IRA), thrombolysis in myocardial infarction (TIMI) flow grade in the IRA, and other angiographic characteristics between patients without and those with chest pain. Multivariable logistic regression model was used to identify independent risk factor of in-hospital mortality.@*Results@#The 2922 (24.1%) patients with STEMI presented without typical chest pain. These patients had a higher TIMI flow grade (mean TIMI flow grade: 1.00 vs. 0.94, P = 0.02) and a lower rate of IRA disease of the left anterior descending artery (44.6% vs. 51.2%, χ2 = 35.63, P < 0.01) than did those with typical chest pain. Patients without chest pain were older, more likely to have diabetes, longer time to hospital and higher Killip classification, and less likely to receive optimal medication treatment and primary percutaneous coronary intervention and higher In-hospital mortality (3.3% vs. 2.2%, χ2 = 10.57, P < 0.01). After adjusting for multi-variables, presentation without chest pain was still an independent predictor of in-hospital death among patients with STEMI (adjusted odds ratio: 1.36, 95% confidence interval: 1.02–1.83).@*Conclusions@#Presentation without chest pain is common and associated with a higher in-hospital mortality risk in patients with acute myocardial infarction. Our results indicate that their poor prognosis is associated with baseline patient characteristics and delayed treatment, but not angiographic lesion characteristics.@*Clinical trial registration@#NCT01874691, https://clinicaltrials.gov.

Angiographic characteristics and in-hospital mortality among patients with ST-segment elevation myocardial infarction presenting without typical chest pain: an analysis of China Acute Myocardial Infarction registry / 中华医学杂志(英文版)

BACKGROUND@#Patients with ST-segment elevation myocardial infarction (STEMI) who present without typical chest pain are associated with a poor outcome. However, whether angiographic characteristics are related to a higher risk of mortality in this population is unclear. This study aimed to investigate whether the higher mortality risk in patients with STEMI without chest pain could be explained by their "high-risk" angiographic characteristics.@*METHODS@#We used data of 12,145 patients with STEMI who was registered in China Acute Myocardial Infarction registry from January 2013 to September 2014. We compared the infarct-related artery (IRA), thrombolysis in myocardial infarction (TIMI) flow grade in the IRA, and other angiographic characteristics between patients without and those with chest pain. Multivariable logistic regression model was used to identify independent risk factor of in-hospital mortality.@*RESULTS@#The 2922 (24.1%) patients with STEMI presented without typical chest pain. These patients had a higher TIMI flow grade (mean TIMI flow grade: 1.00 vs. 0.94, P = 0.02) and a lower rate of IRA disease of the left anterior descending artery (44.6% vs. 51.2%, χ = 35.63, P < 0.01) than did those with typical chest pain. Patients without chest pain were older, more likely to have diabetes, longer time to hospital and higher Killip classification, and less likely to receive optimal medication treatment and primary percutaneous coronary intervention and higher In-hospital mortality (3.3% vs. 2.2%, χ = 10.57, P < 0.01). After adjusting for multi-variables, presentation without chest pain was still an independent predictor of in-hospital death among patients with STEMI (adjusted odds ratio: 1.36, 95% confidence interval: 1.02-1.83).@*CONCLUSIONS@#Presentation without chest pain is common and associated with a higher in-hospital mortality risk in patients with acute myocardial infarction. Our results indicate that their poor prognosis is associated with baseline patient characteristics and delayed treatment, but not angiographic lesion characteristics.@*CLINICAL TRIAL REGISTRATION@#NCT01874691, https://clinicaltrials.gov.

Clinical characteristics of elderly patients with sepsis combined with heart failure and the risk factors analysis / 中华老年医学杂志

Objective To investigate clinical characteristics of elderly patients with sepsis combined with congestive heart failure and risk factors for short-term mortality.Methods Clinical data of elderly patients with sepsis combined with congestive heart failure who were admitted in our hospital from January 2013 to January 2018 were selected and retrospectively analyzed.They were divided into the survival group(n=134)and the death group(n=83)according to survival status during hospitalization.The clinical characteristics and risk factors for mortality were analyzed and compared.Results A total of 217 elderly patients were enrolled,with 113 males and a mean age of(72.3 ± 7.5)years.The death rate of sepsis was 38.3％ (83/217 cases),and 29 cases died of sepsis and 54 cases died of other diseases.Pneumonia accounted for 78.8％ (171/217 patients) in all patients of two groups,and skin and soft tissue infection for 12.9 ％ (28/217 cases).There were significant differences between two groups in age,body mass index,smoking,diabetes,chronic obstructive pulmonary disease,mean arterial pressure,arterial oxygen partial pressure(PaO2),C-reactive protein,white blood cell counts,neutrophil and lymphocyte counts,glomerular filtration rate,serum sodium level,albumin level,lactate level,and left ventricular ejection fraction(P ＜0.05).Furthermore,the rates of invasive mechanical ventilation and continuous renal replacement therapy were higher in the death group than in the survival group(x2=13.209 and 7.402,P＜0.001 and 0.007).Multivariate Cox regression analysis showed that advanced age,chronic obstructive pulmonary disease,low albumin level and low glomerular filtration rate were risk factors for mortality(P＜0.05).Conclusions Elderly patients with sepsis combined with congestive heart failure often have severe pneumonia and violent skin and soft tissue infection,with worse heart and renal function.Advanced age,chronic obstructive pulmonary disease,low albumin level and low glomerular filtration rate are risk factors for mortality.

Study on Adsorption of Two Sulfonamide Antibiotics by Graphene Oxide / 分析化学

Graphene oxide (GO) was prepared by modified Hummers method with graphite as raw materials and used as adsorbent for sulfamethoxazole (SMZ) and sulfamerazine (SMR) in aqueous solutions.The graphene oxide was characterized by fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM).The effects of pH value,adsorption time,initial concentration and temperature on the adsorption property of GO to two sulfonamide antibiotics were investigated and combined with the physical and chemical properties of two kinds of antibiotics.The result showed the maximum adsorption capacity were 138.50 mg/g and 96.06 mg/g at pH=1,adsorbent dosage of 20 mg,45℃,adsorption time of 100 min and 120 min for SMZ and SMR,respectively.The adsorption data of SMZ and SMR fitted well with the Pseudo-second-order kinetics model and the Langmuir isotherm model.The adsorption properties of GO were evaluated with lake water and tap water as real samples and good results were obtained.GO could be used as enrichment and separation materials for sample pretreatment and removing pollutant in wastewater.

Clinical and Coronary Disease Characteristics Among Patients With ST-segment Elevation Myocardial Infarction and Without Typical Chest Pain / 中国循环杂志

Objectives:To explore the clinical and coronary disease characteristics and prognosis of Chinese patients with ST segment elevation myocardial infarction and without typical chest pain. Methods:By extracting data from China Acute Myocardial Infarction Registry, we included 12 145 STEMI patients who underwent coronary angiography between 01 January 2013 to 30 September 2014. Variables of interest were extracted and compared between AMI patients without vs with typical chest pain. Multivariable logistic regression analysis was used to identify independent predictors of in-hospital mortality. Results:There were approximately 24% (2922/12145) STEMI patients without typical chest pain. Compared with typical chest pain patients, patients without typical chest pain had higher prevalence of diabetes (20.0% vs 17.8%), longer time of disease onset to hospital, lower rate of IRA disease of left anterior descending artery (44.6% vs 51.2%). These patients were less likely to receive primary percutaneous coronary intervention (64.9% vs 73.9%) and had higher in-hospital mortality (3.3% vs 2.2%, P＜0.05). Multivarite Logistic regression analysis indicated atypical chest pain was an independent risk factor for in-hospital death (OR:1.364, 95% confidence interval:1.018-1.827). Conclusions:Approximately a quarter STEMI patients presented without typical chest pain in this patient cohort and they had longer disease onset to hospital time, were less likely to receive PCI, and associated with higher in-hospital mortality risk. Efforts should be made to identify these patients in order to apply the optimal treatments to them.

Effect of different time windows and interventions on skin pressure ulcers and ischemia-reperfusion injury in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of different time windows and interventions on skin pressure ulcers and ischemia-reperfusion (I/R) injury in rats.</p><p><b>METHODS</b>Sixty?eight SD rats were randomly divided into blank control group (n=4) and model group (n=64). The rats in the model group were randomly divided into group A (n=32) without intervention and group B (n=32) with post?conditioning. The degree of skin compression, neutrophil infiltration and serum levels of free radicals were observed in the rats after compression for 2, 4, 6, and 8 h (8 rats at each time point).</p><p><b>RESULTS</b>A significant difference was found in the severity of skin damage among the control group, group A, and group B (P=0.001), and the injury was milder in group B than in group A. Severe skin lesions occurred in 2 rats after skin compression for 6 h, as compared with 6 after compression for 8 h (P=0.043), but in none of the rats after compression for 2 or 4. Seventeen rats in group B and 15 in group A showed grade 1 neutrophil infiltration in the skin lesions, and 8 rats in group B and 10 in group A showed grade II neutrophil infiltration (P=0.002). Neutrophil infiltration was the mildest in rats with a 2?h compression, and exacerbated progressively and significantly as the compression time extended (P=0.027). With the prolongation of the intervention time, the rats in both groups A and B showed decreased SOD and increased MDA and NO levels, and overall the I/R injury was milder in 2? and 4?h compression groups than in 6? and 8?h compression groups. The level of serum SOD was significantly higher and MDA and NO levels were significantly higher in group B than in group A (P<0.05).</p><p><b>CONCLUSION</b>Ischemic post?conditioning can relieve I/R injury in acute pressure ulcer in rats. The effective time window for intervention is within 6 h of ischemia, and the effect of ischemic post-conditioning is optimal within 2 h. Ischemic post?conditioning can alleviate free radical injury and inflammation caused by I/R injury.</p>

Sulfated modification and DPPH free radical scavenging ability of polysaccharide from Rhodiola sachalinensis / 中草药

Objective: To optimize the sulfated modification conditions of Rhodiola sachalinensis polysaccharide (RSP) and improve the anti-oxidant activity of RSP. Methods: RSP were sulfated by chlorosulfonic acid-pyridine method, and the optimal conditions for the sulfated modification were determined by single factor experiments. The physical and chemical properties of RSP and sulfated RSP (S-RSP) were analyzed by infrared spectroscopy (IR) and scanning electron microscopy (SEM). The relation between substituting degree (DS) of S-RSP and anti-oxidative activity of polysaccharide was investigated by testing the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging ability of RSP and S-RSP. Results: When the volume ratio of chlorosulfonic acid to pyridine was 1∶4, the reaction time was 2 h and the reaction temperature was 60 ℃, the maximum sulfur content of S-RSP was 18.83% and the DS was the highest for 2.38. Moreover, the anti-oxidant activity of RSP was enhanced by the sulfated modification, and there was a certain positive proportional relationship between DS and DPPH free radical scavenging ability of S-RSP. Conclusion: The volume ratio of chlorosulfonic acid to pyridine affects the DS of S-RSP, and the sulfated modification can increase the anti-oxidant capacity of RSP by changing its polarity.

Effects of Shuxuetongmai Capsule on Expression of p38 MAPK in Rats with Cerebral Ischemia/Reperfusion / 医药导报

Objective To explore the neuroprotection of Shuxuetongmai capsule pretreatment, and the effect on the expression of p38 mitogen-activated protein kinase (p38MAPK) in rats with middle cerebral artery occlusion. Methods Ninety-six male SD rats were divided randomly into sham-operated group,ischemia/reperfusion group (I/R),ischemia preconditioning group (IP),and Shuxuetongmai group(n=24). Each group was further randomly divided into 4 subgroups by 3 h, 6 h, 24 h and 72 h after reperfusion, 6 rats in each subgroup. Sham-operated group was only performed artery separation . The middle cerebral artery occlusion (MCAO) model was set up in I/R rats by Longa method. The IP rats were performed for three minutes on the bilateral carotid artery ligation, and formed MCAO model 24 hours later. The rats in the Shuxuetongmai group were pretreated with Shuxuetongmai capsules for 14 days on gavage before the establishment of MCAO model. The neurological deficits were graded in rats by Zea Longa method. Western Blot was used to determine the protein expression of p38MAPK and P-p38MAPK. Tunel method was applied to detect the apoptosis of neurons and the relationship between expression of p38MAPK, P-p38MAPK and apoptosis of neuron. Results No neurological dysfunction appeared in the sham-operated group at each time points, but not for the other groups, which reached the peak at 24 h. Compared with the I/R group, IP group and Shuxuetongmai group presented the mild neurologic function deficiency at different time points in rats (P0.05). The obvious variation of the value of P-p38MAPK/p38MAPK wasn't detected in sham-operated group at different time points, while obviously presented in I/R group, and the ratios of P-p38MAPK/p38MAPK were increased gradually followed with reperfusion, approaching to the highest level at 24 h. Compared with the I/R group, the P-p38MAPK/p38MAPK declined from 3 h and to the lowest level at 24 h of reperfusion, in both IP and Shuxuetongmai groups(P0. 05). Conclusion Shuxuetongmai capsule pretreatment can induce brain ischemic tolerance, attenuate the apoptosis of neurons in cerebral ischemia reperfusion, and improve neurologic function. The mechanism may be related to the inhibition of p38MAPK phosphorylation.

p15(INK4B) methylation on prognosis and response to decitabine in patients with MDS / 中华血液学杂志

<p><b>OBJECTIVE</b>To detect p15(INK4B) methylation levels and the kinetics of the methylation status before and after decitabine to explore its influences on prognosis and response to decitabine in myelodysplastic syndromes (MDS) patients.</p><p><b>METHODS</b>We examined 261 MDS patients (143 male and 118 female) with the median age of 52 years (32-78). Of them, 172 cases were low-risk group (low-risk 104 cases, intermediate-1 68 cases), 89 cases high-risk group (intermediate-2 52 cases, high risk 37 cases). Collections of bone marrow mononuclear cells of MDS patients and extracted the genomic DNA, the methylation status of p15(INK4B) was detected by methylation-specific PCR (MSP) method. Survival analysis was conducted according to the level of p15(INK4B) methylation in the cohort of patients. The kinetics of the methylation levels of p15(INK4B) in 58 MDS patients before and after 2 courses of decitabine have been assessed with the method of MSP.</p><p><b>RESULTS</b>The methylation level of p15(INK4B) in low-risk group patients was significantly lower than that in high-risk group (117.22 vs 157.63, P<0.05 ). The expected 2-year survival rate of p15(INK4B) methylation positive patients was lower than that of negative ones (91.8% vs 69.8%, P<0.05); the expected 2-year survival rate of p15(INK4B) methylation positive patients was shorter than that of negative ones in low-risk group（78.2% vs 92.0%, P<0.05）, meanwhile there was no significant difference in terms of expected 2-year survival rate and median expected survival between p15(INK4B) methylation positive and negative patients in high-risk group [35.6% vs 38.5%, (17.0±9.3) month vs (18.0±5.7) month, P>0.05]. Multivariate analysis showed p15(INK4B) methylation degree was an independent prognostic factor for overall survival. No statistical difference of overall response (OR) rates were found between p15(INK4B) methylation positive patients and negative patients before decitabine（65.9% vs 76.5%, P>0.05）, and complete remission (CR) rates between these two groups also showed no statistical difference（22.0% vs 29.4%, P>0.05）. p15(INK4B) methylation levels had no obvious change before and after treatment in decitabine responders（P>0.05）.</p><p><b>CONCLUSION</b>The survival of newly diagnosed MDS patients with positive p15(INK4B) methylation was comparatively shorter, but p15(INK4B) methylation had no influence on response to decitabine.</p>

Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate phenotype, cell differentiation and cytogenetic properties of bone marrow (BM) mesenchymal stem cells (MSC) separated from the myelodysplastic syndrome (MDS) patients. And to analyze cytogenetic aberration of MSC derived from MDS (MDS-MSC) and its mechanism in pathogenesis of MDS.</p><p><b>METHODS</b>Adherent MSC from both myelodysplastic (n = 22) and normal (n = 7) marrow were obtained by a stromal culture procedure. Morphological features were observed by optical microscope. The cell-surface antigens were performed by flow cytometer(FCM). Adipogenic and osteogenic differentiation potential of MSC were identified under specific induction conditions. Standard cytogenetic analysis of both hematopoietic cells and MSC were performed by trypsin-Giemsa (GTG) banding. The karyotype analysis DNA content was determined by FCM to verify the results.</p><p><b>RESULTS</b>The morphology of MDS-MSC was typical slender spindle-shaped cells, MSC obtained from MDS patients had a MSC immunophenotype, lacked the expression of hematopoietic antigens-CD34, CD45 and expressed MSC markers, such as CD73, CD90, and CD105. MDS-MSC layers showed the capability to differentiate towards adipocytes, chondrocytes and osteoblasts. Cytogenetic aberrations were observed in MSC from 14 (64%) MDS patients, usually involve the loss of chromosomal material (92%), and the clonal loss (7 cases, 50%). Two cases of structural aberrations were also detected. Abnormal karyotypes in MSC were still more frequently identified in abnormal hematopoietic cells group (12 out of 13, 92% vs 3 out of 9, 33%, P < 0.05). There were not exactly the same type of chromosomal aberrations between hematopoietic cells and MSC, but different type of the aberrations in the same chromosome were involved.</p><p><b>CONCLUSION</b>MDS-MSC retains the phenotyping characteristics and differentiated function of normal MSC, but has different type of chromosomal abnormalities. A high proportion of loss of chromosomal may be a marker of chromosomal instability of MDS-MSC. Detection of abnormalities in MDS-MSC suggests enhanced genetic susceptibility of these cells in MDS. This may indicate potential involvement of MSC in the pathophysiology of MDS.</p>

Current understanding of iron overload hazard in patients with myelodysplastic syndrome / 中国实验血液学杂志

Patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop into transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Thereby our current understanding of the effects of transfusion dependency and iron overload in MDS are discussed. Particular emphasis should be placed on further characterizing the role of redox-active forms of labile iron and oxidative stress in iron overload, decreased life expectancy and increased risk of leukemic transformation in MDS patients with iron overload.

Tissue factor expression of platelets and leukocytes in patients with acute coronary syndromes / 中国实验血液学杂志

The aim of this study was to investigate the tissue factor (TF) expression of platelets and leukocytes in patients with acute coronary syndrome (ACS), patients with stable angina (SA) and healthy subjects (as controls). 26 patients with ACS, 29 patients with SA, and 25 controls were enrolled in this study. The peripheral blood samples of above-mentioned subjects were collected and isolated to obtain the monocytes and platelet-rich plasma, the TF-mRNA expression of monocytes, and platelets among 3 groups was detected by RT-PCR, the TF expression ratio of platelets, platelet-leukocyte aggregates (PLA) and platelet-monocyte aggregates (PMP) was detected by flow cytometry among 3 groups. The results showed that the TF mRNA expression level of platelets in ACS group were significantly higher (3.11 ± 0.51 relative expression) as compared with SA and control groups (1.88 ± 0.78 and 0.7 ± 0.1, respectively) (P = 0.03). Expression of TF mRNA of monocytes was higher in ACS group (P = 0.05 versus controls) too. ACS group had a significantly higher amount of TF-positive platelets (8.8 ± 2.6) than SA (2.6 ± 0.5, P = 0.02) or control groups (2.5 ± 0.4, P = 0.02). A significantly greater number of TF positive platelet-leukocyte aggregates and platelet-monocyte aggregates were also found by flow cytometry in blood of ACS patients than in either SA patients or controls. It is concluded that the high TF expression of platelets and leukocytes in ACS patients strengthens the platelet activation, blood coagulation, and thrombus formation and may further contribute to the hypercoagulability associated with the disease. The present study further extends the proinflammatory/prothrombotic phenotype of ACS patients showing that new players on the scene.

Function of peripheral blood Th17 cells in patients with multiple myeloma / 中国实验血液学杂志

This study was aimed to investigate the effects of peripheral blood Th17 cells and their secreting IL-17, IL-21 in the occurrence and development of multiple myeloma (MM). A total of 55 patients with MM were divided into non-remission group (group A , n = 30), remission group (group B, n = 25); healthy volunteers were used as control group (group C , n = 30). The concentration of IL-17, IL-21 and IL-6 in the peripheral blood mononuclear cell (PBMNC) culture supernatant were determined with ELISA. The ratio of Th7 cells in PBMNC was determined by flow cytometry. The results showed that IL-17, IL-21 levels and ratio of Th17 cells in group A were much higher than those in group B and C (P < 0.05), IL-17, IL-21 and the ratio of Th17 cells between group B and group C were not significantly different (P > 0.05); IL-17 level in non-remission MM group positively correlated with IL-6 level (r = 0.782, P < 0.05), IL-21 level in non-remission MM group positively correlated with IL-6 level (r = 0.778, P < 0.05). It is concluded that Th17 cells as a initiating factor may be involved in the immune pathogenesis of MM patients, promoting the progress of the disease.

Impact of immunochemotherapy on prognostic factors in diffuse large B-cell lymphoma patients / 中国实验血液学杂志

The international prognostic index (IPI) has been established as one of the best predictors of outcome, and several different immunologic subtypes have been established as independent predictors of diffuse large B-cell lymphoma (DLBCL). This study was aimed to reassess and re-evaluate the useful value of these prognostic predictors in patients treated with immunochemotherapy. A retrospective analysis of clinical records of immuno-chemotherapeutic (rituximab + CHOP, R-CHOP) and route chemotherapeutic (CHOP) groups was carried out. Standard two-step method of immunohistochemical staining was used to assess the expression of CD10, MUM-1, BCL-6 and BCL-2. The different classification models (Han's algorithm and Muris model) were performed for patients with DLBCL according to the immunohistochemical staining results in both R-CHOP and CHOP regimen groups. Then the data of remission and overall survival rate in different groups were analyzed to investigate the effect of these prognostic factors. Total 126 de novo DLBCL patients were collected in this study, including 51 patients with treatment of R-CHOP and the other 75 patients with treatment of CHOP. The results showed that the R-CHOP group had higher complete remission rate (68.8) than CHOP group (58.7). The patients with IPI score ≤ 2 had significantly higher overall response rate and overall survival rates than the patients with IPI scores > 2 in both groups. The survival rates of different subtypes in Han's and Muris models were not different from each other in R-CHOP group, but were obvious different from each other in CHOP group. It is concluded that IPI is still effective and predictive for identification of different risk groups. Immunochemotherapy can improve the remission and overall survival rate of DLBCL, but weaken the effect of outcome predictor.