Infiltration of tumor associated macrophages in multiple myeloma and its clinical significance / 中华血液学杂志

Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed. Results: ①Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases (P<0.05). ②In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) (P<0.05), those of relapse refractory group were higher than those of newly diagnosed group (P>0.05). ③Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t=2.362, P=0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t=1.119, P=0.275]. ④TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the non-bortezomib treatment group (18 cases)[(16.52 ±4.26) vs (19.27 ±5.82), t=1.662, P=0.170]. ⑤The TAM infiltration density in MM patients was positively correlated with MVD, VEGF expression level, Treg cell ratio and IL-10 level (P<0.001). Conclusion: The infiltration of TAM in the microenvironment of MM, which may promoting angiogenesis and inhibiting immune response, is related to the occurrence, development, therapeutic effect and drug resistance of MM.

Over-expression of SK2 channel in PVN reduces renal sympathetic nerve activity in chronic heart failure rats / 中国病理生理杂志

[ABSTRACT]AIM:Toinvestigatetheeffectofover-expressionofsmall-conductancecalcium-activatedpotassium channel subtype 2 (SK2) in the paraventricular nucleus (PVN) of hypothalamus on heart rate(HR), mean arterial pres-sure (MAP) and renal sympathetic nerve activity (RSNA) of the rats with chronic heart failure (CHF).METHODS:Adenovirus vector encoding SK2 (pDC316-mCMV-EGFP-rKCNN2) was constructed.The CHF model of the male Sprague Dawley ( SD) rats was established by the ligation of anterior descending coronary artery .Echocardiogram was used at the 6th week after the operation to identify the CHF model .Adenovirus vector encoding SK 2 ( pDC316-mCMV-EGFP-rKCNN2) or control adenovirus vector ( pDC316-mCMV-EGFP) were transfected into the PVN in vivo.The cardiac func-tion was monitored by echocardiogram .The expression of SK2 at mRNA and protein levels was determined by RT-PCR, Western blotting and immunofluorescence .The HR, MAP and RSNA were measured by PowerLab 8/30 in anesthetized rats with bilateral PVN microinjection of SK channel blocker apamin .RESULTS:Treatment with pDC316-mCMV-EGFP-rKC-NN2 significantly decreased the renal sympathetic nerve activity in the rat with CHF .Injection of pDC316-mCMV-EGFP did not change the renal sympathetic nerve activity in the rats in sham group .CONCLUSION:The expression and func-tion of SK channels in PVN in the heart failure rats were decreased , suggesting a reduced negative regulation of sympathetic activity in central neural system .Increased expression of SK 2 in the PVN leads to a reduction in sympathetic outflow under the condition of CHF , which may provide a new target for the treatment of heart failure .

Aliskiren ameliorates sympathetic nerve sprouting and suppresses the inducibility of ventricular tachyarrhythmia in postinfarcted rat heart / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aliskiren is an oral renin inhibitor, which inhibits the first rate limiting step in the renin angiotensin aldosterone system. In this study, sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated.</p><p><b>METHODS</b>Male Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups: angiotensin converting enzyme inhibitor enalapril, angiotensin receptor blocker valsartan, β adrenergic receptor blocker carvedilol and rennin inhibitor aliskiren treatment for six weeks. Electrophysiological study, histological examination and Western blotting were performed.</p><p><b>RESULTS</b>The plasma norepinephrine level and sympathetic nerve innervation significantly increased in treated infarcted rats compared to untreated rats. Aliskiren treatment reduced the sympathetic nerve innervations after myocardial infarction. There is no significant difference in sympathetic nerve innervations after myocardial infarction among the enalapril, valsartan, carvediloand or aliskiren treated groups. Programmed electrical stimulation study showed that inducible ventricular arrhythmia was reduced, ventricular fibrillation threshold was increased and ventricular effective refractory period was prolonged in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats compared to untreated infarcted rats. Cardiomyocytic apoptosis in infarcted region was significantly decreased in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats.</p><p><b>CONCLUSIONS</b>Aliskiren ameliorated cardiomyocytic apoptosis, attenuated the sympathetic nerve innervations and reduced the vulnerability of ventricular arrhythmias after myocardial infarction. Enalapril, valsartan and carvedilol have similar effects as aliskiren on cardiomyocytic apoptosis, sympathetic nerve innervations and vulnerability of ventricular arrhythmias after myocardial infarction.</p>

Identification of a new lamin A/C mutation in a chinese family affected with atrioventricular block as the prominent phenotype / 华中科技大学学报（医学）（英德文版）

Even though mutations in LMNA have been reported in patients with typical dilated cardiomyopathy (DCM) and atrioventricular block (AVB) previously, the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval. Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2, where the LMNA gene was located. Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA, which resulted in an E82K mutation. The E82K mutation co-segregated with all affected individuals in the family, and was not present in 200 normal controls. Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades. Ejection fractions were documented in 5 patients with DCM, but 4 showed a normal value of [Symbol: see text]50%. Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients. This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM. The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.

Study on novel mutations of MEF2A gene in Chinese patients with coronary artery disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the mutations of MEF2A gene in Chinese patients with coronary artery disease(CAD).</p><p><b>METHODS</b>With polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA direct sequencing, the mutation analysis of exon 11 of MEF2A gene was performed to 156 patients with CAD and 93 normal controls.</p><p><b>RESULTS</b>By DNA sequence analyzing the samples of abnormal mobility shift of SSCP, the MEF2A gene mutations were found in three patients with CAD. One of mutations was 147130(C>A)(P431Q), and the second one was 21 bases deletion(147108-147128) which was leading to the absence of 7 amino acids (424QQQQQQQ430), and the third was 147191(G>T). Three mutations were all found in one patient, but meanwhile 21 bases deletion was found in the other two patients.</p><p><b>CONCLUSION</b>Mutations in exon 11 of MEF2A gene exist in the patients with CAD, and the mutations may be pathological.</p>

Relationship between congenital long QT syndrome and Brugada syndrome gene mutation / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the molecular pathology in families with long QT syndrome (LQTS) including Jervell-Longe-Nielsen syndrome (JLNS) and Romano-ward syndrome (RWS) and Brugada syndrome (BS) in Chinese population.</p><p><b>METHODS</b>Polymerase chain reaction and DNA sequencing were used to screen for KCNQ1, KCNH2, KCNE1, and SCN5A mutation.</p><p><b>RESULTS</b>We identified a novel mutation N1774S in the SCN5A gene of the BS family, a novel mutation G314S in a RWS family which had also been found in Europe, North America, and Japan, and a single nucleotide polymorphisms (SNPs) G643S in the KCNQ1 of the JLNS family. In this JLNS family, another heterozygous novel mutation in exon 2a was found in KCNQ1 of the patients.</p><p><b>CONCLUSION</b>New mutations were found in our experiment, which expand the spectrum of KCNQ1 and SCN5A mutations that cause LQTS and BS.</p>

Mutation analysis of a Chinese family with inherited long QT syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the mutation of a Chinese family with inherited long QT syndrome(LQTS).</p><p><b>METHODS</b>The disease-causing gene was tentatively determined in light of the clinical manifestations and electrophysiological properties, and then polymerase chain reaction and DNA sequencing were used for screening and identifying mutation.</p><p><b>RESULTS</b>A missense mutation G940A(G314S) in the KCNQ1 gene was identified, which was the 'hot spot' of long QT syndrome mutation.</p><p><b>CONCLUSION</b>The mutation that is involved with long QT syndrome in Chinese patients is the same as that in the European, American and Japanese patients.</p>

Inhibitory effect of rhynchophylline on human ether-a-go-go related gene channel / 生理学报

We studied the effects of Chinese traditional medicine rhynchophylline (Rhy) on human ether-a-go-go related gene (HERG) channel and characterized the electrophysiological properties of Rhy's pharmacological effect on HERG channel using Xenopus oocytes. Xenopus oocytes were injected with either 23 nl (5.75 ng) HERG cRNA or 23 nl distilled water. Xenopus oocytes were randomly assigned to receive one of the following different concentrations of Rhy: (1) control, (2)10 mumol/L Rhy, (3)100 mumol/L Rhy, (4) 500 mumol/L Rhy, (5) 1 000 mumol/L Rhy, (6) 10 000 mumol/L Rhy. Cell currents were recorded in oocytes. The peak tail currents of HERG channel were inhibited by Rhy. The inhibition was in a dose-dependent manner [IC(50)=(773.4 +/- 42.5) mumol/L]. Experiment with 100 mumol/L Rhy indicated that the degree of HERG blockade showed some voltage dependence (within -40 mV to -20 mV ). Kinetic analyses revealed that Rhy decreased the rate of channel activation. The findings indicate that Rhy inhibits HERG encoded potassium channels. It may underline the molecular mechanism of myocardial electrophysiological characteristics associated with this drug.

Losartan inhibits renal sympathetic nerve activity in Paraventricular nucleus in chronic heart failure rat / 中国临床药理学与治疗学

AIM:Left coronary artery ligation(LAD)was used to induce heart failure.Losartan was microinjected into paraventricular nucleus(PVN),heart rate(HR),blood pressure(BP)and renal sympathetic nerve activity(RSNA)were measured.The mechanism of PVN in chronic heart failure was investigated.METHODS:Sprague-Dawley male rats were selected for LAD ligation for heart failure models,the variation of cardiac function was detected by echocardiography.Losartan was microinjected into PVN,the responses of HR,BP and RSNA were analyzed.RESULTS:Compared with sham group,the level of LV was increased(P

Inhibitory effect of interferon ?-2b on atherosclerosis / 中国病理生理杂志

AIM: To evaluate the effects of interfer ?-2b (IFN ?-2b ) on atherosclerosis(AS).METHODS: Thirty normal male rabbits were randomly divided into five groups:normal control group(NC group, n= 6), atherosclerosis group(AS group, n =6),virus (herpesvirus Ⅰ,HSV-Ⅰ)infected atherosclerosis group(V group, n= 6), interferon (interferon ?-2b) intervented atherosclerosis group (IFN-Ⅰgroup, n= 6),interferon intervented and virus infected atherosclerosis group (IFN-Ⅱ group, n= 6). Serum lipids were measured and the thoracic aortas were sampled for histopathological, immunohistochemical and in situ hybridization study. RESULTS: The aorta atherosclerosis areas of NC, IFN-Ⅰ and IFN-Ⅱ groups were lower than that of AS group significantly, respectively, and the area of AS group was lower than that of V group ( P