Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology / 中国实验血液学杂志

OBJECTIVE@#To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.@*METHODS@#The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.@*RESULTS@#The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).@*CONCLUSION@#A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

The relationship of serum albumin level and early-onset sepsis in very low birth weight infants / 中国新生儿科杂志

Objective:To study the predictive value of serum albumin (ALB) on the first day of life for early-onset sepsis (EOS) in very low birth weight infants (VLBWI).Methods:From January 2015 to December 2020, clinical data of VLBWI (gestational age < 34 weeks, birth weight < 1 500 g) born and hospitalized in our hospital were collected. Based on the serum ALB level at admission, the infants were assigned into high, moderate and low ALB groups. C-reactive protein (CRP) and procalcitonin (PCT) levels among different ALB groups were compared. The infants were also assigned into EOS and non-EOS groups according to the occurrence of EOS and perinatal complications were compared between the two groups. The relationship between EOS and ALB level was analyzed. The predictive value of serum ALB was studied using receiver operating characteristic (ROC) curve analysis.Results:A total of 183 infants were enrolled, including 62 in the high ALB group, 87 in the moderate ALB group and 34 in the low ALB group; and 36 in EOS group and 147 in non-EOS group. The incidence of maternal chorioamnionitis was significantly higher in EOS group than non-EOS group [33.3% (12/36) vs. 6.8% (10/147), P<0.001]. Serum CRP and PCT in the low and moderate ALB groups were significantly higher than the high ALB group ( P<0.05), and the low ALB group showed higher CRP and PCT than the moderate ALB group ( P<0.05). Compared with the non-EOS groups, ALB in the EOS group was significantly lower [24.9 (24.0, 28.5) g/L vs. 29.5 (27.4, 31.2) g/L, P<0.001] and the incidence of hypoproteinemia was significantly higher [52.8% vs.10.2%, P<0.001]. As ALB decreased, the incidence of EOS increased. The incidence of EOS was 55.9% in the low ALB group, 16.1% in the moderate ALB group and 4.8% in the high ALB group ( P<0.001). The sensitivity and specificity of ALB predicting EOS was 69.4% and 79.6%, respectively, with a cut-off value of 27.0 g/L. Conclusions:The VLBWI with maternal chorioamnionitis and serum albumin lower than 27.0 g/L on the first day of life have higher risk of EOS.

3-lead electrocardiography and pulse oximetry in early heart rate assessment of high-risk neonates / 中华围产医学杂志

Objective:To compare the accuracy and timeliness of 3-lead electrocardiography (ECG) and pulse oximetry (POX) in neonatal heart rate (HR) monitoring after birth.Methods:This prospective study recruited 42 high-risk newborns with gestational age ≥37 weeks and birth weight >1 500 g who were born through cesarean section without resuscitation requirement in Xi'an People's Hospital (Xi'an Fourth Hospital) from October 2019 to August 2020. 3-lead ECG electrodes and POX sensors were attached to the neonates immediately after drying to continuously monitor the HR within 10 min after birth. All procedure was recorded by video camera, and data were independently analyzed by a clinician after the procedure was completed. Differences in time required to connect the devices, time to obtain a reliable HR and the interval between them, the time needed for obtaining a reliable HR after birth, the proportion of neonates with reliable HR obtained within 5 min after birth and the consistency in the reliable HR readings between the two devices were compared using Wilcoxon signed-rank test, McNemar test, Spearman's correlation coefficient, intraclass correlation coefficient or Bland-Altman bias analysis.Results:The median time required to connect POX and 3-lead ECG and to acquire a reliable HR were 13.0 s (10.0-17.0 s) vs 23.0 s (18.0-28.3 s) ( Z=-5.050, P<0.001), and 79.5 s (56.2-128.0 s) vs 11.0 s (10.0-13.3 s) ( Z=-5.646, P<0.001), respectively. The total time from the beginning of connecting the devices and birth to acquiring a reliable HR were both longer for POX than those for 3-lead ECG [92.0 s (71.3-139.0 s) vs 35.0 s (30.0-39.5 s), Z=-5.579, P<0.001; 110.5 s (85.8-153.5 s) vs 52.0 s (45.0-66.3 s), Z=-5.579, P<0.001]. Reliable HRs were obtained in 69.1% (29/42) and 2.4% (1/42) of the infants by 3-lead ECG and POX within 1 min after birth, respectively. The percentage of infants for obtaining a reliable HR detected by 3-lead ECG within 5 min after birth were more than those by POX, but with statistically significant differences only at the first 60 s, 90 s, 120 s and 150 s (all P<0.001). The median HRs obtained by 3-lead ECG and POX within 10 min after birth were 161 beats/min (147-175 beats/min) and 160 beats/min (146-176 beats/min), respectively ( r=0.966, P<0.001). The mean difference of HR detected by the two devices was 0.56 beats/min (95% CI:-4.3 to 5.4 beats/min). The intraclass correlation coefficient was 0.961, showing good internal consistency. Conclusions:Neonatal HR can be assessed accurately by 3-lead ECG within 1 min after birth, which is far earlier than that by POX. Therefore, 3-lead ECG can be an option for continuously HR monitor in neonatal resuscitation.

Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL).@*METHODS@#Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People's Hospital from February 2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX (3.5 g/m@*RESULTS@#There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed.@*CONCLUSION@#The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite short-term effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.

Diagnostic value of 18F-FDG PET/CT and tumor markers (CEA, CA19-9, CA24-2) in recurrence and metastasis of postoperative colorectal moderately differentiated adenocarcinoma / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the diagnostic value of 18F-FDG PET/CT and tumor markers (CEA,CA19-9,CA24-2) in detection for recurrence and metastasis of postoperative colorectal moderately differentiated adenocarcinoma.@*METHODS@#Fifty-five patients were enrolled in this study. All of the patients were tested with serum CEA within 2 weeks when they underwent 18F-FDG PET/CT scan, and some patients were tested with serum CA19-9 and CA24-2 simultaneously. According to the pathology and clinical results of their follow-up, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT and tumor markers were calculated based on different divided groups, respectively.@*RESULTS@#According to the pathology and the results of their clinical follow-up, the sensitivity of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 95.74%, 68.09%, 28.57%, 40.00% and 74.47%, respectively. The specificity of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 75.00%, 50.00%, 66.67%, 71.43% and 50.00%, respectively. The positive predictive valueof 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 95.74%, 88.89%, 85.71%, 88.89% and 89.74%, respectively. The negative predictive value of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 75.00%, 26.67%, 11.42%, 17.24%, 25.00%, respectively. The accuracy of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 92.73%, 65.47%, 32.65%, 44.68% and 70.91%, respectively. There were 2 cases of false positive and 2 cases of false negative in 18F-FDG PET/CT.@*CONCLUSION@#18F-FDG PET/CT has high value in detecting recurrence and metastasis of postoperative colorectal carcinoma. Tumor markers have the positive value to imply the recurrence and metastasis of postoperative colorectal carcinoma and are useful to indicate when to perform the 18F-FDG PET/CT. The combination of tumor markers could improve the diagnostic efficiency to some extent.

Lipoxin A4 Ameliorates Lipopolysaccharide-Induced A549 Cell Injury through Upregulation of N-myc Downstream-Regulated Gene-1 / 中华医学杂志(英文版)

<p><b>Background</b>Lipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4.</p><p><b>Methods</b>A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-α/γ. Candidate genes affected by LXA4 were explored by transcriptome sequencing of A549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis of A549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor (ALX) inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-α expression. Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression.</p><p><b>Results</b>The A549 cell models of ALI were constructed and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream-regulated gene-1 (NDRG1) was validated by real-time-PCR and Western blot. NDRG1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG1 expression induced by LXA4. NDRG1 siRNA suppressed viability of LPS-treated A549 cells (treatment vs. control, 0.605 ± 0.063 vs. 0.878 ± 0.083, P = 0.040) and ENaC-α expression (treatment vs. control, 0.458 ± 0.038 vs. 0.711 ± 0.035, P = 0.008). LY294002 inhibited NDRG1 (treatment vs. control, 0.459 ± 0.023 vs. 0.726 ± 0.020, P = 0.001) and ENaC-α (treatment vs. control, 0.236 ± 0.021 vs. 0.814 ± 0.025, P < 0.001) expressions and serum- and glucocorticoid-inducible kinase 1 phosphorylation (treatment vs. control, 0.442 ± 0.024 vs. 1.046 ± 0.082, P = 0.002), indicating the PI3K signaling pathway was involved in regulating NDRG1 expression induced by LXA4.</p><p><b>Conclusion</b>Our research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression.</p>

"Discussion on Yu Chang′s Medical Moral Thoughts Characterized by Highlighting the Criterion Based on ""Medical Laws""" / 中国医学伦理学

Yu Chang,a famous doctor in Qing dynasty,puts a high value on criterion, which is the most impor-tant characteristic in his medical moral thoughts. Based on the traditional medical moral, Yu Chang quoted Buddha into medicine and further expounded the medical moral criterion ( restrain the doctors by laws) referring to Buddhist commandment. This article analyzed the detailed medical moral criterion and requirements of carefulness,per-fection,honestyand pursuing the truththat mentioned in Medical Laws. Furthermore, it pointed out the es-sential features and significance of Yu Chang′s medical moral thoughts.

Chemical constituents from ethyl acetate extract of Shiaria bambusicola / 中国中药杂志

Fourteen compounds were isolated and purified from the ethyl acetate of the ethanol extract of Shiaria bambusicola by various chromatographic methods, and their structures were elucidated by spectral techniques and physicochemical properties as hypocrellin A (1), hypocrellin B (2), hypocrellin C (3), hypomycin A (4), ergosterol (5), ergosterol peroxide (6), (22E, 24R)-5alpha, 8alpha-epidioxy-6,9(11),22-trien-3beta-ol (7), ergosta-7, 24(28)-dien-3beta-ol (8), (22E, 24R)-ergost-7, 22-dien-3beta, 5alpha, 6beta-triol (9), (22E,24R)-ergosta-7, 22-diene-3beta, 5alpha, 6beta-triol-3-O-palmitate (10), (22E, 24R)-ergosta-7, 22-diene-3beta, 5alpha, 6beta-triol-6-O-palmitate (11), 1-O-monostearin (12), 1, 3-O-distearin (13), and mannitol (14). Among them, compounds 7-13 were firstly isolated from this genus.

Application of Qu single abdominal aorta clamping for bloodless hepatectomy and Pringle hepatectomy in 118 cases of liver tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the results of application of Qu single abdominal aorta clamping for bloodless hepatectomy and Pringle hepatectomy in 118 cases of liver tumors.</p><p><b>METHODS</b>The clinical data of 118 patients, including 59 patients undergoing Qu single abdominal aorta clamping for bloodless hepatectomy (Group QG) and 59 patients undergone Pringle first hepatic portal clamping hepatectomy (Group PG) since March 2009 in the Ningbo Tumor Hospital and Jiangxi Provincial Hospital were retrospectively reviewed. The changes of blood pressure, oxygen saturation, urine volume, intravenous fluid volume, amount of bleeding, time of abdominal aorta (or first hepatic portal) clamping, duration of operation and anesthesia, and other intraoperative indexes of the two groups were compared, and the changes of peritoneal drainage, blood tests, liver functions, etc. before operation and 1, 3, 7, 14 days after the hepatectomy in the two groups were also analyzed.</p><p><b>RESULTS</b>After taking appropriate measures for intraoperative blood pressure control, only small fluctuations of blood pressure, which could be safely adjusted and controlled with stable vital signs, was observed in the group QG. The amount of intraoperative bleeding in the group QG was (96.25 ± 18.45) ml, significantly less than (536.25 ± 35.65) ml in the group PG (P < 0.05). In the group QG, both the duration of operation time [(227.58 ± 28.20) min] and duration of anesthesia [(249.48 ± 31.35) min] were significantly shorter than that [(261.46 ± 32.12) min and (286.58 ± 35.62) min, respectively] in the group PG (both P < 0.05). The postoperative liver dysfunction in the group QG was also milder than that in the group PG (P < 0.05).</p><p><b>CONCLUSIONS</b>For liver tumor patients, Qu single abdominal aorta clamping for bloodless hepatectomy can basically achieve the goal of bloodless hepatectomy. This surgical operation is simple and safe, worthy of recommendation to skillful liver surgeons in hospitals there are some difficulties of blood supply.</p>

99Tcm-MDP whole body bone imaging in 25 patients with SAPHO syndrome / 中华核医学杂志

Objective To investigate the usefulness of 99Tcm-MDP whole body bone scintigraphy (WBBS) in patients with synovitis,acne,pustulosis,hyperostosis,osteitis (SAPHO) syndrome.Methods 99Tcm- MDP WBBS was performed in 25 patients (6 males,19 females,mean age =(55.1 ±9.8) years)with SAPHO syndrome.Bone lesions were classified into five categories:anterior chest wall,spine,mandible,sacroiliac joint,and limbs.The typical scintigraphic manifestations of SAPHO syndrome were summarized and compared to other radiological imaging data.Results Among 25 patients,32％ of cases (8/25)were associated with skin lesion; 48％ ( 12/25 ) were pathologically diagnosed with chronic nonspecific bone inflammation by bone biopsy.On 99Tcm-MDP WBBS,abnormal metabolic foci at anterior chest wall were found in all cases,most of which located in the sternocostoclavicular region (96％,24/25 ),including sternoclavicular joints (60％,15/25),first costosternal junctions (48％,12/25),and manubriosternal junctions (44％,11/25 ).Only 20％ of the patients (5/25) demonstrated the typical scintigraphic characteristic:“bull's head” sign.The second most frequent part was spine (44％,11/25).Appendicular skeleton was affected in 16％ (4/25) patients.WBBS also demonstrated additional skeletal lesions in 68％ (17/25 ) of the patients,mainly in first costosternal junctions (7 patients),sternoclavicular joints (6 patients),manubriosternal junctions (5 patients) and spine (4 patients).Conclusions Abnormal metabolic foci in sternocostoclavicular region and other imaging manifestations on 99Tcm- MDP WBBS can be used to diagnose,differentiate,and localize the insidious lesion and evaluate the lesion activity in patients with SAPHO syndrome.

Effects of recombinant human erythropoietin on serum levels of neuron-specific enolase, S-100β protein and myelin basic protein in rats following status epilepticus / 中国当代儿科杂志

<p><b>OBJECTIVE</b>This study examined the effect of recombinant human erythropoietin (r-HuEPO) on the serum levels of neuron-specific enolase (NSE), S-100β protein and myelin basic protein (MBP) in young rats 24 hrs after lithium-pilocarpine-induced status epilepticus (SE) in order to study the potential role of r-HuEPO in epileptic brain damage.</p><p><b>METHODS</b>Forty 19-21-day-old male Sprague-Dawley (SD) rats were randomly divided into four groups (n=10): normal control group, SE, r-HuEPO pretreated-SE and r-HuEPO. SE was induced by lithium-pilocarpine. R-HuEPO (500 IU/kg) was intraperitoneally injected in the r-HuEPO pretreated-SE and r-HuEPO groups 4 hrs before SE. Serum levels of NSE, S-100β and MBP were determined 24 hrs after the SE event.</p><p><b>RESULTS</b>Serum levels of NSE, S-100β and MBP in the SE group increased significantly compared with those in the normal control and the r-HuEPO groups (P＜0.05). The r-HuEPO pretreated-SE group showed significantly decreased serum levels of NSE, S-100β and MBP compared with the SE group (P＜0.05).</p><p><b>CONCLUSIONS</b>r-HuEPO may reduce the expression of NSE, S-100β and MBP and thus might provide an early protective effect against epileptic brain injury.</p>

Morphine treatment enhances extracellular ATP enzymolysis and adenosine generation in rat astrocytes / 生理学报

Recent studies have shown that astrocytes play important roles in ATP degradation and adenosine (a well known analgesic molecule) generation, which are closely related to pain signaling pathway. The aim of this study was to investigate whether morphine, a well known analgesic drug, could affect the speeds of ATP enzymolysis and adenosine generation in rat astrocytes. Intracellular calcium concentration ([Ca(2+)](i)) of astrocyte was measured by flow cytometry, and the time points that morphine exerted notable effects were determined for subsequent experiments. Cultured astrocytes were pre-incubated with morphine (1 μmol/L) and then were incubated with substrates, ATP and AMP, for 30 min. The speeds of ATP enzymolysis and adenosine generation were measured by high performance liquid chromatography (HPLC). The results showed that both 1.5 and 48 h of morphine pre-incubation induced maximal ATP enzymolysis speed in astrocytes among all the time points, and there was no statistical difference of ATP enzymolysis speed between morphine treatments for 1.5 and 48 h. As to adenosine, morphine pre-incubation for 1.5 h statistically increased adenosine generation, which was degraded from AMP, in cultured astrocytes compared with control group. However, no difference of adenosine generation was observed after 48 h of morphine pre-incubation. These results indicate that treatment of morphine in vitro dynamically changes the concentrations of ATP and adenosine in extracellular milieu of astrocytic cells. In addition, astrocyte can be regarded as at least one of the target cells of morphine to induce changes of ATP and adenosine levels in central nervous system.

Effect of hydrogen sulfide on expression of survivin and its neuroprotective function in PC12 cells / 中华神经医学杂志

Objective To explore the effect of hydrogen sulfide (H2S) on the expression of survivin in PC12 cells and the neuroprotective function of H2S on PC12 cells.Methods Different concentrations of sodium hydrosulfide (NaHS) were used to treat the PC12 cells at different times.Dose-effect (50-800 μmol/L) and time-effect (0-180 min) on the expression of survivin were evaluated by Western blotting.Cell viability was tested by using cell counter kit-8.Results NariS treatment at the concentrations from 50 to 200 μmol/L for 30 min could up-regulate the expression of survivin in a dose dependent manner,however,when the concentration of NariS was above that,the expression of survivin decreased gradually;when the concentration of NariS reached 800 μmoi/L,the expression level of survivin was lower than the normal level.Treatment with 400 μmol/L NariS within the range of 0-60 min could promote the expression of survivin in a time dependent manner,but with the extension of time,the expression of survivin was declined.On the other hand,400 μmol/L NaHS preconditioning could enhance the expression of survivin promoted by CoCl2 and reduce the injuries of PC12 cells induced by CoCl2 to increase the cell viability.Conclusion H2S increases the expression ofsurvivin in a dose and time dependent manners at certain degree,which may be related to the protection of PC12 cells against chemical hypoxic damage.

ERK1/2 mediates edaravone-triggered protection against myocardial damage induced by isoprenaline in H9c2 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of extracellular signal regulated kinase 1/2 (ERK1/2) on edaravone (EDA)-triggered protection against myocardial toxicity induced by isoprenaline (ISO) in H9c2 myocardial cells (H9c2 cells).</p><p><b>METHODS</b>H9c2 cells were exposed to ISO at different concentrations to establish a cardiac toxicity model induced by persistent excitation of β1 receptor. EDA was added before ISO as a pretreatment. PD-98059, an ERK1/2 inhibitor, was administered 1 h prior to EDA to inhibit the phosphorylation of ERK1/2. Cell viability was measured using cell counter kit (CCK-8). The expressions of p-ERK1/2 and t-ERK1/2 were tested by Western blotting. Mitochondrial membrane potential (MMP) was detected by Rhodamine123 (Rh123) staining and photofluorography.</p><p><b>RESULTS</b>Exposure of H9c2 cells to 80 µmol/L ISO for 24 h down-regulated ERK1/2 phosphorylation and repressed MMP. Pretreatment with 10-40 µmol/L EDA for 1 h inhibited ISO-induced myocardial toxicity and pretreatment of 40 µmol/L EDA partially rescued ERK1/2 phosphorylation and MMP level. PD-98059 abolished cardiac protection of EDA, leading to myocardial toxicity and MMP loss.</p><p><b>CONCLUSION</b>EDA can protect H9c2 cells against myocardial injury induced by ISO by suppressing ISO-triggered inhibition of ERK1/2 activation.</p>

Pharmacophore modeling of dual angiotensin II and endothelin A receptor antagonists / 药学学报

Three-dimensional pharmacophore models were generated for AT1 and ET(A) receptors based on highly selective AT1 and ET(A) antagonists using the program Catalyst/HipHop. Both the best pharmacophore model for selective AT1 antagonists (Hypo-AT(1)-7) and ETA antagonists (Hypo-ET(A)-1) were obtained through a careful validation process. All five features contained in Hypo-AT(1)-7 and Hypo-ET(A)-1 (hydrogen-bond acceptor (A), hydrophobic aliphatic (Z), negative ionizable (N), ring aromatic (R), and hydrophobic aromatic (Y)) seem to be essential for antagonists in terms of binding activity. Dual AT1 and ET(A) receptor antagonists (DARAs) can map to both Hypo-AT(1)-7 and Hypo-ET(A)-1, separately. Comparison of Hypo-AT(1)-7 and Hypo-ET(A)-1, not only AT1 and ET(A) antagonist pharmacophore models consist of essential features necessary for compounds to be highly active and selective toward their corresponding receptor, but also have something in common. The results in this study will act as a valuable tool for designing and researching structural relationship of novel dual AT1 and ET(A) receptor antagonists.

Reactive oxygen species scavenger protects cardiac cells against injuries induced by chemical hypoxia / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of reactive oxygen species (ROS) scavenger, N-acetyl-L-cysteine (NAC), against H9c2 cardiomyocytes from injuries induced by chemical hypoxia.</p><p><b>METHODS</b>H9c2 cells were treated with cobalt chloride (CoCl2), a chemical hypoxia-mimetic agent, to establish the chemical hypoxia-induced cardiomyocyte injury model. NAC was added into the cell medium 60 min prior to CoCl2 exposure. The cell viability was evaluated using cell counter kit (CCK-8), and the intercellular ROS level was measured by 2', 7'- dichlorfluorescein-diacetate (DCFH-DA) staining and photofluorography. Mitochondrial membrane potential (MMP) of the cells was observed by Rhodamine123 (Rh123) staining and photofluorography, and the ratio of GSSG/ (GSSG+GSH) was calculated according to detection results of the GSSG kit.</p><p><b>RESULTS</b>Exposure of H9c2 cardiomyocytes to 600 micromol/L CoCl2 for 36 h resulted in significantly reduced cell viability. Pretreatment with NAC at the concentrations ranging from 500 to 2000 micromol/L 60 min before CoCl2 exposure dose-dependently inhibited CoCl2-induced H9c2 cell injuries, and obviously increased the cell viability. NAC at 2000 micromol/L obviously inhibited the oxidative stress induced by CoCl2, decreased the ratio of GSSG/(GSSG+GSH), increased ROS level, and antagonized CoCl2-induced inhibition on MMP.</p><p><b>CONCLUSION</b>NAC offers obvious protective effect on H9c2 cardiomyocytes against injuries induced by chemical hypoxia by decreasing in the ratio of GSSG/(GSSG+GSH) and ROS level and ameliorating MMP.</p>

Genetic polymorphisms of MC2R gene associated with responsiveness to adrenocorticotropic hormone therapy in infantile spasms / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Infantile spasms is a severe epileptic encephalopathy, which is refractory to conventional antiepileptic drugs. Adrenocorticotropic hormone (ACTH) has been the major therapy for infantile spasms; however, ACTH therapy is ineffective for some patients. The variations in the receptor genes can contribute to antiepileptic drug resistance. This study was to elucidate the possible associations between the variations of the MC2R gene and ACTH responsiveness in patients with infantile spasms.</p><p><b>METHODS</b>We screened for variations in the promoter and coding region of the MC2R gene in 91 Chinese patients with infantile spasms and 94 controls, using PCR and a direct sequencing method. The frequencies of the genotypes, alleles and reconstructed haplotypes were analyzed in the cases and controls. The association between ACTH responsiveness and genetic variations of the MC2R gene was also assessed.</p><p><b>RESULTS</b>Four single nucleotide polymorphisms (SNPs) were identified in the MC2R promoter, one of which was a novel specimen at position-2 from the transcription start site ATT, -2T > C. Three SNPs (rs1893220, rs2186944 and -2T > C) showed a significant difference between the cases and controls (P < 0.05 for all). The frequency of the common TCCT haplotype carrying four-SNP major alleles was significantly lower in the cases (39%) than in the controls (60%) (P = 0.00003). The homozygous carriers of the TCCT haplotype had a much lower relative risk than the non-carriers (RR = 0.42, 95% CI 0.26-0.70, P = 0.0001). ACTH responsiveness was strongly associated with the TCCT haplotype (P = 0.000082). Compared with non-carriers of the TCCT haplotype, the homozygous and heterozygous carriers were more responsive to ACTH therapy (P = 0.0002; P = 0.0003, respectively).</p><p><b>CONCLUSIONS</b>Our results indicated that the TCCT haplotype in the MC2R promoter is strongly associated with the responsiveness of the ACTH therapy performed on patients with infantile spasms. The polymorphisms of the MC2R promoter might be one important factor that influences the efficacy of ACTH therapy on infantile spasms.</p>

High-sensitivity C-reactive Protein,Pulse Pressure and Microalbuminuria in Patients with Essential Hypertension / 中华高血压杂志

Objective To investigate the relationship between high-sensitivity C-reactive protein(hsCRP), pulse pressure(PP) and microalbuminuria(MAU) in patients with essential hypertension.Methods Consecutive 60 patients with essential hypertension were classified based on the MAU level:patients with MAU(n=30) and the group of patients with normoalbuminuria(NMAU,n=30) with 30 healthy subjects as control.MAU,hsCRP,PP were determined.Results The level of hsCRP and pulse pressure in MAU group were higher than those in NMAU patients and healthy subjects (P

Effects of prostate water pellets on the serum levels of IL-6 and TNF-alpha in rats with chronic bacterial prostatitis / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Prostate Water Pellets (PWP) on serum levels of IL-6 and TNF-alpha in rats with chronic bacterial prostatitis (CBP).</p><p><b>METHODS</b>Fifty healthy, adult, male Wistar rats with the weight of 180 - 220 g were divided into five groups of ten rats each at random: the control group, model group, high dosage of PWP group, low dosage of PWP group and levofloxacin group. The CBP rat model were created by injecting Escherichia coli (0.2 ml/rat, 10(7)/ml) into prostates. A month later after the model creation, high and low dosage of PWP suspension were used by gavage in CBP rats for 30 days, respectively. Levofloxacin tablets were used by gavage as the positive control, and distilled water was used by gavage in the control and model group. After thirty days, serum levels of IL-6 and TNF-alpha were measured with radioimmunoassay.</p><p><b>RESULTS</b>Compared with the model group, serum levels of IL-6 and TNF-alpha of rats in high and low dosage PWP groups were lower and the difference was significant statistically (P < 0.01).</p><p><b>CONCLUSION</b>It has effect to treat CBP rat with the PWP and its mechanism may relate with the decreasing levels of proinflammatory cytokines(IL-6 and TNF-alpha) in blood.</p>

Design,Applications and Effects of "Multimedia Paper of Microbiology Experiment" / 微生物学通报

Based on improving experimental operating skills of students and considering the features of microbiology experimental technology and methods,we developed a new examination ways of microbiology experiment — "multimedia papers of microbiology experiments" to use among 2005 and 2006 students of sophomore(entering campus in 2005 and 2006) of biotechnology and bio-science for microbiology experiment examination.Analysis of the results of experiment examination and theoretical examination for the 2005 and 2006 students showed that the disharmony and miscorrelation between experiment examination results and theoretical examination results were overcome,and students got more interested in experimental classes,while their experimental operation is more conscious and accurate.