The Latest Research Progress of Selinexor in the Treatment of Non-Hodgkin Lymphoma --Review / 中国实验血液学杂志

Non-Hodgkin lymphoma (NHL) is a common lymphoid hematological malignancy, the treatment and prognosis of NHL have always been the focus of clinical attention. Chemotherapy is the main first-line treatment, but there is still no effective treatment for patients with poor response to chemotherapy, recurrence or progression within a short period of time after treatment, and new and effective drugs need to be developed clinically. As the only clinically validated oral selective inhibitor of nuclear export (SINE), Selinexor has been approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma and multiple myeloma, clinical attempts are being made to apply it to the treatment of other hematological malignancies.This article reviews the anti-tumor mechanism of Selinexor and the latest research progress in its application in NHL, and provides ideas for a more diverse, standardized and effective applications of Selinexor in NHL.

Polypeptide from Moschus Suppresses Lipopolysaccharide-Induced Inflammation by Inhibiting NF-κ B-ROS/NLRP3 Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice.@*METHODS@#The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively.@*RESULTS@#The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs.@*CONCLUSION@#PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

Modified Qiaohetang and Xiehuangsan in Treatment of Acne Due to Dampness-heat Accumulation / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Qiaohetang and Xiehuangsan in the treatment of acne due to dampness-heat accumulation and its influence on the levels of inflammatory factors and sex hormones. Method:One hundred and sixty-eight eligible patients were divided into an observation group （84 cases） and a control group （84 cases） according to the random number table. Adapalene gel was applied externally in both groups， one time per day. In the control group， Jinhua Xiaocuo pills was taken orally， 4 g per time， three times a day. In the observation group， the modified Qiaohetang and Xiehuangsan was provided for oral administration， one bag per day. The treatment lasted for eight weeks. The Global Acne Grading System （GAGS） score， skin lesion count， dampness-heat accumulation syndrome score， and Dermatology Life Quality Index （DLQI） score were recorded before and after treatment， followed by the detection of interleukin-8 （IL-8）， IL-10， IL-17， interferon-<italic>γ</italic> （IFN-<italic>γ</italic>）， free testosterone （FT）， estradiol （E₂） and sex hormone binding globulin （SHBG） before and after treatment as well as the safety evaluation. Result:The GAGS， dampness-heat accumulation syndrome， and DLQI scores of the observation group were lower than those of the control group （<italic>P</italic><0.01）. The counts of inflammatory skin lesions （papule and pustule）， non-inflammatory skin lesions， and total skin lesions in the observation group declined in contrast to those in the control group （<italic>P</italic><0.01）. The IL-8， IL-17， IFN-<italic>γ</italic> and FT levels of the observation group were decreased as compared with those of the control group （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the IL-10， E₂， and SHBG levels were increased （<italic>P</italic><0.01）. The overall response rate in clinical symptom alleviation of the observation group was 93.67%（74/79）， which was higher than 81.82%（63/77） of the control group （<italic>χ</italic>²=5.121， <italic>P</italic><0.05）. The overall response rate in dampness-heat accumulation syndrome relief of the observation group was 92.41% （73/79）， still higher than 79.22% （61/77） of the control group （<italic>χ</italic>²=5.595， <italic>P</italic><0.05）. No adverse reactions occurred after the oral administration of Chinese medicinal preparations. Conclusion:The modified Qiaohetang and Xiehuangsan combined with adapalene gel can reduce the skin lesion count and severity， relieve both clinical symptoms and dampness-heat accumulation syndrome， regulate the inflammatory response and sex hormones， and improve the quality of life of patients with acne of dampness-heat accumulation syndrome without inducing side effects.

Advances on hormone-like activity of Panax ginseng and ginsenosides / 中国天然药物

Traditional Chinese medicine (TCM) has been paid much attentions due to the prevention and treatment of steroid hormone disorders. Ginseng, the root of Panax ginseng C. A. Meyer (Araliaceae), is one of the most valuable herbs in complementary and alternative medicines around the world. A series of dammarane triterpenoid saponins, also known as phytosteroids, were reported as the primary ingredients of Ginseng, and indicated broad spectral pharmacological actions, including anti-cancer, anti-inflammation and anti-fatigue. The skeletons of the dammarane triterpenoid aglycone are structurally similar to the steroid hormones. Both in vitro and in vivo studies showed that Ginseng and its active ingredients have beneficial hormone-like role in hormonal disorders. This review thus summarizes the structural similarities between hormones and dammarane ginsenosides and integrates the analogous effect of Ginseng and ginsenosides on prevention and treatment of hormonal disorders published in recent twenty years (1998-2018). The review may provide convenience for anticipate structure-function relationship between saponins structure and hormone-like effect.

Effects of Atorvastatin, Rosuvastatin, and Pravastatin on Antiplatelet Activity of Clopidogrel in Patients with Acute Coronary Syndrome and Different CYP2C19 Genotypes / 中国药学杂志

OBJECTIVE: To investigate the effects of atorvastatin, rosuvastatin, and pravastatin on antiplatelet activity of clopidogrel in patients with acute coronary syndrome(ACS) and different CYP2C19 genotypes. METHODS: Between November 2017 and November 2018, a total of 300 patients admitted for ACS were enrolled in this study and randomly assigned to three groups. All patients received standard dual antiplatelet therapy. A, B, and C groups received atorvastatin calcium 20 mg•d-1, rosuvastatin calcium 20 mg•d-1, and pravastatin sodium 20 mg•d-1, respectively. The CYP2C19 genotype was detected by pyrosequencing. Thromboelastogram(TEG) was applied to detect the ADP-induced platelet inhibition rate 7 days after treatment. RESULTS: No significant difference was observed in baseline clinical characteristics between three groups. It was also no statistically significant difference in ADP inhibition rate and proportion of clopidogrel resistance between three groups(P>0.05). However, compared with rosuvastatin group and pravastatin group, the ADP inhibition rate was significantly reduced in atorvastatin group in poor metabolizers of CYP2C19. CONCLUSION: In intermediate metabolizers and extensive metabolizers of CYP2C19, there is no significant difference in the effects of atorvastatin, rosuvastatin, and pravastatin on antiplatelet activity of clopidogrel. Compared with rosuvastatin and pravastatin, atorvastatin significantly attenuates the antiplatelet function of clopidogrel in poor metabolizers of CYP2C19.

Progress in vaccine development based on baculovirus expression vector system / 生物工程学报

Baculovirus expression vector system (BEVS) has been successfully applied to the over-expression of various proteins, thus providing sufficient materials for vaccine research. Compared to other systems, BEVS has many advantages: baculovirus solely being parasitic in invertebrates, the resultant products conferring high safety to mammalian, high expression level of recombinant proteins, preferable folding for eukaryotic protein, proper post-translational modification required for biological function, suitable for multiple genes co-expression and large-scale production with serum-free culture media. To better understand the advantages and prospective of BEVS for the vaccine research, this article will review the development of BEVS and its application on vaccine research.

Effects of Arsenic Trioxide on Cdc20 and Mad2 in Acute Myeloid Leukemia HL-60 Cell Line / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of arsenic trioxide (AsO) on Cdc20 and Mad2 in process of AML HL-60 cell proliferation.</p><p><b>METHODS</b>The proliferation of HL-60 cells was detected by CCK-8 method at different concentrations of arsenic trioxide for 24, 48 and 72 hours. The cell morphological changes were observed by inverted microscopy. The expressions of Mad2 and Cdc20 mRNA and protein in HL-60 cells treated with AsO for 48 h were detected by real-time PCR and Western blot respectively.</p><p><b>RESULTS</b>Arsenic trioxide significantly inhibited the HL-60 cell proliferation and displayed a good time-dose correlation. RT-PCR and Western blot showed that the expression of Mad2 was up-regulated and the expression of Cdc20 was down-regulated in HL-60 cells treated with arsenic trioxide of different concentration (4,8,10 µmol/L).</p><p><b>CONCLUSION</b>Arsenic trioxide can inhibit the human acute myeloid leukemia HL-60 cell proliferation, and its mechanism may be related with up-regulation of Mad2 expression and down-regulation of Cdc20 expression.</p>

New method for evaluating pharmacodynamics of traditional Chinese medicine compounds based on its moderate regulation and principle of balanced adjustment of immunity under pan-immunomic / 中国中药杂志

For the basic research on the traditional Chinese medicine(TCM), objective syndrome of traditional Chinese medicine and evaluation criteria of traditional Chinese medicine compounds are hardly to break though. While, the modern immunology points out that the body is a counterbalance state and immune imbalance is the root of sickness. The thinking mode of treating diseases in traditional Chinese medicine is also "balance", considering disease is the result of bias which present the imbalance of "Yin counters Yang", "exterior counters interior", "cold counters heat" and "weak counters strong". The Chinese herbal compound formula preparation was applied on disease therapy based on theory of Chinese medicine, which was confirmed by long period clinical application. It is composed of multi-compounds and has the characteristic of multi-targeting. Integrative medicine has spawned pan-immunomics, and the evaluation of immune function (immune balance) has become an important basis for diagnosis and treatment models of integrative medicine. In addition, balance is the core idea of whole-systemic conception of traditional Chinese medicine. Therefore, we speculate that immune balance under pan-immunomic can bridge the traditional Chinese medicine and modern integrative medicine and is the important basis for objective syndrome of traditional Chinese medicine and evaluation criteria of traditional Chinese medicine compounds. According to the bridging theory, we attempt to utilize informatics and statistical methods to construct an evaluation system for pharmacodynamics of traditional Chinese medicine based on its moderate regulation and the balanced adjustment of immunity under pan-immunomic, which further reveal the scientific essence of the whole-systemic view of traditional Chinese medicine. This research brings out a new valuable strategy and provides a theoretical basis for accelerating the transformation of traditional Chinese medicine, especially the exploitation of Chinese herbal compound formula, and constructing the new drug innovation and review system for traditional Chinese medicine. Besides as a reference for traditional Chinese medicine objective syndrome and pharmacodynamics of traditional Chinese medicine compounds, the evaluation system can screen the immunity of sub-health population also. With the continuous accumulation of clinical sample and data, the evaluation system will be more accurate and intelligent.

Telomere Length, Expression of MRE11 and Ku80 in Patients with Aplastic Anemia and Their Correlation with Pathogenesis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect the expression levels of MRE11 and Ku80 mRNA, and telomere length in bone marrow mononuclear cells of aplastic anemia(AA) patients, and to explore their correlation with pathogenesis of aplastic anemia.</p><p><b>METHODS</b>Bone marrow mononuclear cells were collected from 40 cases of AA and 20 normal controls for detecting mRNA expression of MRE11 and Ku80 and telomere length by using real-time quantitative polymerase chain reaction (qPCR), then MRE11, Ku80 and telomere length were analyzed for their correlation.</p><p><b>RESULTS</b>As compared with controls, the expression levels of MRE11 and Ku80 in patients with AA were significantly reduced, and the telomere length in patients with AA was obviously shortened, respectively (P<0. 05). The telomere length was significantly shorter in the persons aged ≥45 years in comparison with the AA patients and normal control younger than 45 years old (P<0.05). For the AA patients older than or equal to 45 years and less than 45 years in comparison with the controls at the same age, the telomere length was significantly shorter(P<0.05). The expression levels of MRE11 and Ku80 didn't correlate with telomere length (P>0.05). The mRNA expression level of MRE11 correlated positively and significantly with that of Ku80 (r=0.863, P<0.05).</p><p><b>CONCLUSION</b>The change of telomere length may play an important role in the pathogenesis and progression of aplastic anemia. The lower expression of MRE11 and Ku80 may be involved in the pathogenesis of aplastic anemia.</p>

Genotypes of adenoviruses in infants and young children with diarrhea / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of adenoviruses (AdV) and their genotypes in infants and young children with diarrhea.</p><p><b>METHODS</b>A total of 380 children with diarrhea aged less than 3 years were enrolled. The genomic DNA was extracted from stool and PCR was used to detect AdV. Clone sequencing and genotyping were performed for DNA in AdV-positive specimens.</p><p><b>RESULTS</b>AdV was detected in 24 out of 380 specimens, and the detection rate was 6.3% (24/380). A majority of children with positive AdV were aged 2-3 years. The viral sequence analysis of positive specimens showed that the detection rates of enteric AdV41 and non-enteric AdV were 4.2% (16/380) and 2.1% (8/380), respectively, and among the children with non-enteric AdV, there were 2 with AdV1, 2 with AdV2, 1 with AdV7, 2 with AdV12, and 1 with AdV31.</p><p><b>CONCLUSIONS</b>Diarrhea caused by AdV is commonly seen in children aged 2-3 years, and AdV41 is the major predominant strain.</p>

Analysis of TERT and TIN2 Gene Expression in Patients with Acquired Aplastic Anemia and Their Correlation with Pathogenesis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect the mRNA expression levels of TERT and TIN2 in peripheral blood mononuclear cells of acquired aplastic anemia(AAA) patients, and to explore their correlation with pathogenesis of acquired aplastic anemia.</p><p><b>METHODS</b>Peripheral blood mononuclear cells of 40 cases of AAA including 33 cases of non-severe aplastic anemia(NSAA), 7 cases of severe aplastic anemia (SAA) and 20 subjects as control group were collected to detect mRNA expression of TERT and TIN2 by using real-time quantitative polymerase chain reaction(RT-qPCR), the correlation of TERT and TIN2 mRNA expression levels with classification of peripheral blood cells were analyzed.</p><p><b>RESULTS</b>The expression levels of TERT and TIN2 mRNA in patients with AAA were lower significantly than those in control group (P<0.05), and the SAA (P<0.01). The expression levels of TERT and TIN2 mRNA in patients with SAA were all lower significantly than those in patients with NSAA (P<0.05). The expression levels of TIN2 mRNA in patients with NSAA were lower significantly than those in control group (P<0.01). There were no significant difference in the expression level of TERT mRNA between patients with NSAA and control group (P=0.082). There was significant correlation between the expression level of TERT mRNA and red blood cells count (r=0.437, P=0.029), and hemoglobin level (r=0.522, P=0.007). There was significant correlation between the expression levels of TIN2 mRNA and the lymphocyte percentage (r=-0.404, P=0.045).</p><p><b>CONCLUSION</b>The expression level of TERT mRNA may be associated with the red blood cells and hemoglobin level. The expression level of TIN2 mRNA may be associated with the lymphocyte percentage.</p>

Sorting of side population cells from multiple myeloma cell lines and analysis of their biological characteristics / 中国实验血液学杂志

This study was aimed to sort the side population (SP) cells from human multiple myeloma cell lines, then detect the biological characteristics of those SP cells. After Hoechst33342 staining, intracellular Hoechst33342 fluorescence staining differences of myeloma cell lines observed by the fluorescence microscopy. The fluorescence-activated cell sorting (FACS) technology was used to isolate SP cells and main population (MP) cells; proliferative capacity in vitro was determined by cell growth curve; the cell colony forming ability was compared by colony forming test. The CD138 expression was detected by flow cytometry. The expression of ABCG2 mRNA was detected by reverse transcription PCR; CCK-8 assay and colony forming test were used to evaluate the effect of bortezomib on the cell proliferation, vitality and colony forming ability of the two populations. The results showed that the myeloma cell lines had a small proportion of SP cells, especially, RPMI 8226 cells accounted for the highest proportion of SP cells (7.10 ± 2.69)%, which have also been confirmed under the fluorescence microscope; the proliferative activity and cell colony forming ability of SP cells were significantly higher than those of MP cells (P < 0.05). The expression levels of CD138 in SP and MP cells were not significantly different (P > 0.05). RT-PCR results showed that SP cells expressed the drug-resistance gene ABCG2, but MP cells hardly express these genes. The inhibition rate of bortezomib on SP cells was significantly lower than that on MP cells (P < 0.05), however, the difference was not significant (P > 0.05) at bortezomib 40 nmol/L. Bortezomib could reduce colony formation in the both two cell populations, but more severe reduction appeared in the MP cells. It is concluded that the myeloma cell line contain a small amount of SP cells with the cancer stem cell characteristics.

Effects of down-regulated TRAF6 gene expression on the proliferation and apoptosis in multiple myeloma cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the down-regulated TRAF6 gene expression and its effects on proliferation and apoptosis in multiple myeloma (MM) cells.</p><p><b>METHODS</b>Detection of TRAF6 expression were conducted by RT-PCR and Western blot in MM cell lines of KM3, U266, RPMI8226 and primary cells from patients. RPMI8226 cell lines were transfected with siRNA of TRAF6. The efficiency of transfection was identified by using of fluorescence microscope, RT-PCR, and Western blot. The levels of proliferation were analyzed by CCK-8 method under the different concentrations of siRNA. Apoptosis rate were detected with Hoechst33258/PI double staining by flow cytometry. Apoptosis related proteins Bcl-2, BAX, and NF-κB signal pathway were observed before and after siRNA transfection by Western blot.</p><p><b>RESULTS</b>The levels of TRAF6 mRNA and protein in MM cell lines, especially in primary myeloma cells, were significantly higher than those in controls. After transfected with 50 nmol/L siRNA in RPMI8226 cells, the relative level of TRAF6 mRNA (0.49±0.24) was significantly lower than that in non-transfected group (1.87±0.23) and idling group (1.74±0.35). The proliferation rate of siRNA transfected cells decreased with dose dependence (P<0.01). The apoptosis rates increased from 11.20% (before transfection) to 51.82% (after transfection), accompanied by down-regulated Bcl-2 protein, NF-κB signal pathway (p-p65 and p52), and up-regulated BAX protein.</p><p><b>CONCLUSION</b>TRAF6 expression was high in myeloma cells. TRAF6 siRNA could inhibit proliferation of myeloma cells and induce apoptosis mediated by NF-κB classical and alternative pathway in myeloma cells.</p>

Expression of TRF1, TRF2 and RAP1 mRNA in peripheral blood mononuclear cells of patients with acquired aplastic anemia / 中国实验血液学杂志

This study was aimed to investigate the expression levels of TRF1, TRF2 and RAP1 mRNA in peripheral blood mononuclear cells of patients with acquired aplastic anemia, and to explore their relation with onset of acquired aplastic anemia. Peripheral blood mononuclear cells of 40 patients with acquired aplastic anemia and 20 normal subjects as control were collected to detect mRNA expression of TRF1, TRF2 and RAP1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of TRF1 and RAP1 in peripheral blood mononuclear cells of patients with acquired aplastic anemia were significantly higher than that in normal controls (P < 0.05), while the expression level of TRF2 was lower than that in normal controls (P < 0.01). There was significant correlation between TRF2 and RAP1 expressions level (r = 0.522, P = 0.001). It is concluded that the changes in expression levels of TRF1, TRF2 and RAP1 may play a role in the pathogenesis of acquired aplastic anemia.

Mathematic model of respiratory mechanics based on monitored physiological parameters / 医用生物力学

Objective To establish a model of respiratory mechanics with consideration of gas exchange and directly correlate with the gas content in blood during mechanical ventilation with the mechanics of respiratory system. Methods By coupling the physiological parameters of respiratory system and blood circulation system, including the molecular numbers of oxygen and carbon dioxide in alveoli and clinically monitored physiological parameters such as gas content, hemoglobin content, heart rate and cardiac output, a mechanical model was constructed to predict those dynamic parameters of gas content, pressure and flow rate in airway and alveoli in continuous breathing cycles. Results The gas content in different locations of a respiratory system was estimated by the model and the sensitivity of gas content in expiration to the undetermined parameters was evaluated. Conclusions The model of respiratory mechanics developed in the study is a preliminary attempt to predict the regulation roles of physiological parameters clinically monitored during mechanical ventilation, which will provide a theoretical support for the design and development of novel respirators in the follow-up experiment.

Study on the correlation between Chinese medical syndrome types and ID4 gene promoter methylation in human acute myeloid leukemia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the correlation between Chinese medical syndrome type (CMST) and the ID4 gene promoter methylation state in the bone marrow cells of acute myeloid leukemia (AML) patients, and to discuss the correlation between ID4 gene methylation and the occurrence, development of AML.</p><p><b>METHODS</b>Thirty-five inpatients or outpatients from the Department of Hematology, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were recruited as the test group, while 10 healthy volunteers from the health medical center of the Affiliated Hospital, Shandong University of Traditional Chinese Medicine were recruited as the control group. The ID4 gene promoter methylation states were detected using methylation specific polymerase chain reaction (MS-PCR) in the two groups. Inter-group comparison was performed and CMSTs were compared to analyze the correlation between CMSTs and the gene promoter methylation.</p><p><b>RESULTS</b>Twenty-seven AML patients (77.1%) had methylation of ID4 gene, showing statistical difference when compared with the control group (P < 0.01). The ID4 methylation positive rate of ID4 gene promoter methylation was sequenced from low to high as qi and yin deficiency syndrome < inter-accumulation of blood stasis and phlegm syndrome < toxic heat inflaming syndrome, showing statistical difference when compared with the control group (P < 0.05). The peripheral white blood cells and the bone marrow blast cells were higher in ID4 methylation positive patients than in the ID4 methylation negative control patients with statistical difference (P < 0.05).</p><p><b>CONCLUSIONS</b>Patients of inter-accumulation of blood stasis and phlegm syndrome and toxic heat inflaming syndrome were more likely to have ID4 gene methylation. The ID4 methylation positive expression has verified the essence of evil domination in the early AML at the molecular level. It can also reflect the degree of malignancy of AML to some extent.</p>

Electrophysiological effects of hydrogen sulfide on human atrial fibers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that endogenous or exogenous hydrogen sulfide (H(2)S) exerts physiological effects in the vertebrate cardiovascular system. We have also demonstrated that H(2)S acts as an important regulator of electrophysiological properties in guinea pig papillary muscles and on pacemaker cells in sinoatrial nodes of rabbits. This study was to observe the electrophysiological effects of H(2)S on human atrial fibers.</p><p><b>METHODS</b>Human atrial samples were collected during cardiac surgery. Parameters of action potential in human atrial specialized fibers were recorded using a standard intracellular microelectrode technique.</p><p><b>RESULTS</b>NaHS (H(2)S donor) (50, 100 and 200 µmol/L) decreased the amplitude of action potential (APA), maximal rate of depolarization (V(max)), velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF), and shortened the duration of 90% repolarization (APD(90)) in a concentration-dependent manner. ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide (Gli, 20 µmol/L) partially blocked the effects of NaHS (100 µmol/L) on human atrial fiber cells. The L-type Ca(2+) channel agonist Bay K8644 (0.5 µmol/L) also partially blocked the effects of NaHS (100 µmol/L). An inhibitor of cystathionine γ-lyase (CSE), DL-propargylglycine (PPG, 200 µmol/L), increased APA, V(max), VDD and RPF, and prolonged APD(90).</p><p><b>CONCLUSIONS</b>H(2)S exerts a negative chronotropic action and accelerates the repolarization of human atrial specialized fibers, possibly as a result of increases in potassium efflux through the opening of K(ATP) channels and a concomitant decrease in calcium influx. Endogenous H(2)S may be generated by CSE and act as an important regulator of electrophysiological properties in human atrial fibers.</p>

ID4 promoter methylation in acute myeloid leukemia / 中国实验血液学杂志

Objective of this study was to investigate the ID4 gene methylation status in patients with acute myeloid leukemia (AML). Methylation-specific PCR (MS-PCR) was used to detect the promoter methylation status of ID4 gene in bone marrow samples from 46 AML patients with different subtypes and stage of disease and from 10 patients with iron deficiency anemia (IDA) as a control. The results showed that ID4 gene in bone marrow of IDA patients was completely non-methylated, while ID4 gene methylation was found in 39 out of 46 AML patients (positive rate 84.8%). The positive rates of ID4 gene methylation in different FAB types M₁, M₂, M₃, M₄, M₅, M₆ were 100% (4/4), 75% (9/12), 100% (8/8), 77.8% (7/9), 81.8% (9/11), 100% (2/2) respectively. The positive rates of ID4 gene methylation in newly diagnosed and complete remitted of AML patients were 90% (27/30) and 63.3% (7/11) respectively; ID4 methylation was detected in 5 relapsed and refractory AML patients. There were statistically significant differences in ID4 gene methylation between AML and IDA patients (p < 0.01). It is concluded that compared with IDA patients, ID4 gene methylation changes of different degrees occur in AML patients with different subtypes and stages, which suggests that ID4 gene methylation may be an early molecular event in the process of AML.

The effect of Crocin against hypoxia damage of myocardial cell and its mechanism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of Crocin against hypoxia damage of cardiac myocytes of neonatal rats and the regulation of HIF-1 and prolyhydroxylase (PHDs).</p><p><b>METHODS</b>A model of CoCl2 simulated hypoxia damage was established in primary cultural myocardial cell. Expression levels of HIF-1alpha, VEGF, iNOS, as well as PHD1, 2, 3 protein in myocardial cells were detected by Western blot.</p><p><b>RESULTS</b>Compared with CoCl2 group, the viability of myocardial cell was significantly increased after treated 24 h at 10(-5)mol/L Crocin (P < 0.01), HIF-1alpha, VEGF and iNOS were expressed higher than those in Crocin + CoCl2 group (P < 0.01), the expression of PHD2 was significantly increased (P < 0.01), while the expression of PHD3 was remarkably reduced in Crocin + CoCl2 Group (P < 0.01).</p><p><b>CONCLUSION</b>Crocin has better protective effect on hypoxic damage of myocardial cell. The mechanisms of protective effect of Crocin may be related to the activation of HIF-1-mediated pathway of the hypoxia response. PHDs may be involved in the pathophysiology regulated process of myocardial cells.</p>

Influences of Panax notoginsenosid on spontaneous contraction of small intestine smooth muscle of rabbits in vitro / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the influences of Panax notoginsenosid(a compound of Chinese Traditional Medicine) on the spontaneous contraction of small intestine smooth muscle of rabbits in vitro and explore the mechanism.</p><p><b>METHODS</b>The influences of Panax notoginsenosid on the spontaneous contraction of small intestine in intacted rabbits(male or female) after the isothermal perfuse of small intestine in vitro were observed. Bay K8644 and nitro-L-arginine methylester (L-NAME) were added to the normal Tyrode's solution respectively before Panax notoginsenosid. In the Ca2+ free Tyrode's solution, rynodine was added before Panax notoginsenosid. The mechanism of Panax notoginsenosid was studied.</p><p><b>RESULTS</b>Panax notoginsenosid reduced the amplitude of contraction of small intestine smooth muscle in rabbits in a does-depended manner. Bay K8644 and L-NAME could completely block the inhibition of Panax notoginsenosid on the contraction of small intestine smooth muscle. Panax notoginsenosid inhibited significantly the intracellular calcium-depended contraction induced by rynodine in the Ca2+ free Tyrode's solution.</p><p><b>CONCLUSION</b>Panax notoginsenosid inhibits significantly the contraction of small intestine smooth muscle of rabbits in vitro. The mechanism may be related to increase NO concentration in small intestine smooth muscle so that inhibit extracellular Ca2+ inflowing via cell membrane and intracellular Ca2+ releasing via sarcoplasmic reticulum.</p>