Curative Efficacy of Rituximab for ITP Patients with Different Sensitivity to Hormone / 中国实验血液学杂志

OBJECTIVE@#To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant.@*METHODS@#Seventy-ninth ITP patients enrolled in this study included the glucocorticoid-ineffective patients (19 cases) and glucocorticoid-dependent patients (60 cases). All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab (dexal-methasone 40 mg/d for 4 days per os, ritaximab 100 mg by intravenous infusion at D7, 14, 21 and 28 respectively). The patients after treatment were followed-up for 12 month, and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed. The changes of Treg cell ratio and BAFF, IL-2 and sCD40L levels before and after treatment were detected by flow cytometry and ELISA respectively.@*RESULTS@#The overall response rate (ORR) of patients treated with above- mentioned regemen at 1, 3, 6 and 12 months after treatment was 79.7% (63/79), 69.6% (55/79), 63.3% (50/79) and 60.8% (48/79) respectivcly, out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1, 3, 6 and 12 months after treatment was 47.4% (9/19) vs 90.0% (54/60), 36.8% (7/19) vs 80.0% (48/60), 21.1% (4/19) vs 76.7% (46/60), 21.1% (4/19) vs 73.3% (44/60), and the difference between 2 groups was statistically significant. The detection of T reg cell showed that the T reg cell ratio in glucocorticoid- ineffective and dependent patients at 1, 3, 6 and 12 months after treatment was (1.70±0.43)% vs (3.47±0.72)%, (1.66±0.33)% vs (4.29±0.91)%, (1.71±0.37)% vs (4.44±0.97)%, (3.36±0.54)% vs (4.29±1.04)%, respectively. The detection of cytokines showed that the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased (P＜0.05), the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment, but there was no statistical difference as compared with glucocosticoid-depenment patients.@*CONCLUSION@#The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective. The regulatory effect of rituximab on the T-reg cells, BAFF, IL-2 and sCD40L may be one of its mechanisms.

Effect of Neuronal Excitability in Hippocampal CA1 Area on Auditory Pathway in a Rat Model of Tinnitus / 中华医学杂志(英文版)

Background@#Tinnitus is a common disorder that causes significant morbidity; however, the neurophysiological mechanism is not yet fully understood. A relationship between tinnitus and limbic system has been reported. As a significant component of the limbic system, the hippocampus plays an important role in various pathological processes, such as emotional disturbance, decreased learning ability, and deterioration of memory. This study was aimed to explore the role of the hippocampus in the generation of tinnitus by electrophysiological technology.@*Methods@#A tinnitus model was established in rats through intraperitoneal injection of salicylate (SA). Subsequently, the spontaneous firing rate (SFR) of neurons in the hippocampal CA1 area was recorded with in vivo multichannel recording technology to assess changes in excitability induced by SA. To investigate the effect of excitability changes of hippocampus on the auditory pathway, the hippocampus was electrically stimulated and neural excitability in the auditory cortex (AC) was monitored.@*Results@#Totally 65 neurons in the hippocampal CA1 area were recorded, 45 from the SA group (n = 5), and 20 from the saline group (n = 5). Two hours after treatment, mean SFR of neurons in the hippocampal CA1 area had significantly increased from 3.06 ± 0.36 Hz to 9.18 ± 1.30 Hz in the SA group (t = -4.521, P 0.05). In the AC, 79.3% (157/198) of recorded neurons showed responses to electrical stimulation of the hippocampal CA1 area. Presumed pyramidal neurons were excited, while intermediate neurons were inhibited after electrical stimulation of the hippocampus.@*Conclusions@#The study shows that the hippocampus is excited in SA-induced tinnitus, and stimulation of hippocampus could modulate neuronal excitability of the AC. The hippocampus is involved in tinnitus and may also have a regulatory effect on the neural center.

Effect of Lentiviral Vector-Mediated CXCR4 Gene Overexpression on Mesenchymal Stem Cell Homing Capacity / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effects of lentiviral-mediated CXC chemokine receptor-4（CXCR-4）gene over-expression on the homing capacity of mesenchymal stem cells（MSC）in vivo.</p><p><b>METHODS</b>The MSC overexpressing CXCR-4 were constructed by using the lentiviral vector-mediated mouse MSC overexpressing the CXCR-4 gene. The BALB/c mice were divided into 3 group: simple radiation group（TBI）in which mice exposed to total body irradiation, then were infused with normal saline; EGFP-MSC group in which mice were infused with MSC（5×10）transducted by EGFP via tail vein after TBI; and CXCR-4-MSC group in which mice were infused with MSC (5×10) simultaneously carraying EGFP and CXCR-4 gene via tail vein after TBI. The mice were sacrified at 24 hours after infusion, the frozen sections were prepared to detect the distribution of infused MSC. Furthermore, the numbers of MSC homing into spleen and bone marrow was detected by flow cytometry, and the level of stromal cell-derived factor-1(SDF-1) was detected by ELISA.</p><p><b>RESULTS</b>The frozen section showed that the CXCR-4 over-expression could significantly enhance the efficacy of MSC homing into lung, liver and spleen; the flow cytonetry detection slowed that the number of over-expressed CXCR-4 MSC homing into spleen and bone matrow was sigmificantly higher than that in EGFP-MSC group（P<0.05）, the ELISA showed that the SDF-1 level in peripheral blood and bone marrow after 24 hours of irradiation significantly incrtaoed （P<0.05）, moreover, the SDF-1 level increase was associcted with horming efficacy of MSC with CXCR-4 overexpression.</p><p><b>CONCLUSION</b>overexpression CXCR-4 gene mediated by lentiviral vector can prmote the efficacy of MSC homing into spleen and bone marrow.</p>

Research Progress on Effect of JAK Inhibitors on Myelofibrosis- Review / 中国实验血液学杂志

Myelofibrosis(MF) is a type of myeloprolifirative neoplasms which is difficult to be treated. With the discovery of V617F mutation site in Janus kinase 2 (JAK2), JAK inhibitor provides a new treatment strategy for patients with myelofibrosis. Since 2011 the FDA in USA approved the first generation of JAK inhibitor Ruxolitinib for marketing, a growing number of JAK inhibitors have been entering into the clinical trials and showed a certain clinical efficacy. On the one hand, some JAK inhibitors for single application can effectively relieve the clinical symptoms of patients with myelofibrosis, slow down disease progression, and prolong the survival; on the other hand, JAK inhibitor can also be applied in combination with traditional or other new targeted drugs for MF patients, even during the allogenetic hematopoietic stem cell transplantation, thus providing more choices for targeted therapy on the patients with myelofibrosis. This review focuses mainly on the latest advances of JAK inhibitors for the patients with myelofibrosis.

Absorption properties and mechanism of trolline and veratric acid and their implication to an evaluation of the effective components of the flowers of Trollius chinensis / 中国天然药物

AIM@#To study the absorption properties and mechanism of two important components, trolline and veratric acid, from the flowers of Trollius chinensis, in order to better understand the contribution of these two compounds to the effectiveness of these flowers.@*METHOD@#The human Caco-2 cell monolayer model was employed to study the transport of trolline and veratric acid from apical side (AP) to basal side (BL), and from BL to AP by determining the transport rates as the function of time and concentration and calculating apparent permeability coefficients (Papp).@*RESULTS@#Trolline and veratric acid were transported across Caco-2 cell monolayer through different mechanisms in a concentration dependent manner. Trolline was transported at a Papp level of 10(-6) cm·s(-1) with a Papp AP→BL/Papp BL→AP ratio of more than 1.8 or less than 0.8, while veratric acid was transported at a Papp level of 10(-5)cm·s(-1) with a Papp AP→BL/Papp BL→AP ratio of close to 1.0.@*CONCLUSION@#Trolline is moderately absorbed through an associative mechanism involving active and passive transport, and veratric acid is well-absorbed mainly through passive diffusion. These factors should be taken into account when chemically assessing the pharmacodynamic material basis of the flowers of T. chinensis.

A 65-year-old man with infratentorial diffuse encephalopathy and hydrocephalus / 中华医学杂志(英文版)

Tuberculous encephalopathy (TBE) is an important diagnosis in countries with a high prevalence of tuberculosis. TBE is a life-threatening condition but rarely reported in the modern literature. We reported a case of a man with extensive parenchymal lesions involving the brainstem and right cerebellar hemisphere that resolved after treatment. The clinical, laboratory and pathological features of this case are highlighted and the pathogenesis is discussed.

Expression of MIF, VEGF and p16 proteins and their correlation with clinicopathological features in cervical cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of macrophage migration inhibitory factor (MIF), p16 and vascular endothclial growth factor (VEGF) proteins and their relationship with clinicopathological features in cervical cancer.</p><p><b>METHODS</b>Tissue microarray (TMA) and immunohistochemistry were used to detect the expression of MIF, p16 and VEGF proteins in specimens of 10 normal cervical epithelial tissues, 18 cervical intraepithelial neoplasia (CIN II, III) and 31 cervical squamous cell carcinomas. Western blotting was used to detect the expression of MIF, p16 and VEGF proteins in fresh samples of 3 normal cervical epithelial tissues, 3 CIN (III) and 6 cervical squamous cell carcinomas (3 Ib and 3 IIb).</p><p><b>RESULTS</b>Positive expression rates of MIF were 0, 72.2% and 93.5% in the normal, CIN and carcinoma samples, 20.0%, 33.3% and 71.0% for p16, and 10.0%, 44.4% and 74.2% for VEGF, respectively. The expression rates and levels of the three genes were significantly higher in cervical carcinomas than those in CIN. MIF expression was significantly higher in the cases with lower differentiation (17 cases, P = 0.021), and was positively correlated with VEGF expression (P = 0.0045). VEGF expression rate was significantly higher in both cases of poorly differentiated carcinomas and those with stage II b carcinoma or beyond (P = 0.004, P = 0.008). p16 expression was not found to be correlated with tumor differentiation or clinical stage. It was showed by Western blotting that the expression levels of MIF, VEGF and p16 were significantly higher in the carcinomas than those in CIN or normal tissues.</p><p><b>CONCLUSION</b>Expression of MIF, VEGF and p16 are probably involved in the process of cervical carcinogenesis. MIF expression is correlated with tumor differentiation. VEGF expression is correlated with both tumor differentiation and clinical stage.</p>

Change of extracellular ascorbic acid in the brain cortex following ice water vestibular stimulation: an on-line electrochemical detection coupled with in vivo microdialysis sampling / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ascorbic acid (AA) represents one of the most important enzyme co-factors, antioxidants and neuromodulators and plays an important role in the cerebral system. Increasing evidence has suggested that AA could treat certain kinds of vertigo diseases such as Meniere's disease. To elucidate the neurochemical functions associated with AA in vertigo, the change of extracellular AA in the brain cortex following caloric vestibular stimulation (CVS) was evaluated.</p><p><b>METHODS</b>An on-line electrochemical detection was coupled with in vivo microdialysis to continuously monitor the change of extracellular AA in the primary somatosensory (SI) area of guinea pigs following a caloric vestibular stimulation. Sixteen guinea pigs were divided into three groups, i.e., experimental group with irrigation of the ear canal with ice water (0 degrees C) (n = 8), and two control groups, one with irrigation of the ear canal with warm water (38 degrees C) (n = 4) and the other with irrigation of the auricle with ice water (n = 4).</p><p><b>RESULTS</b>In the experimental group, the ice water irrigation of the left external ear canal induced a horizontal nystagmus towards the right side lasting about 45 seconds. No nystagmus was induced by warm water irrigation of the external ear canal or by ice water irrigation of the auricle. The extracellular AA concentration significantly increased following the ice water vestibular stimulation, reaching a maximum of (130 +/- 20)% (n = 8) of the basal dialysate level (2.61 +/- 0.92) micromol/L (n = 8), lasting at least for an hour. AA level did not change distinctly after the irrigation of the left external ear canal with warm water or the irrigation of the auricle with ice water.</p><p><b>CONCLUSIONS</b>The concentration of extracellular AA in the brain cortex of the SI area increased following the ice water vestibular stimulation. This demonstration may be useful for the investigation of the neurochemical processes associated with AA in the process of vertigo.</p>

Effects of caloric vestibular stimulation on serotoninergic system in the media vestibular nuclei of guinea pigs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Anatomic and electrophysiological studies have revealed that the neurons located in the media vestibular nuclei (MVN) receive most of the sensory vestibular input coming from the ipsilateral labyrinth and the responses of MVN neurons to caloric stimulation directly reflect changes in primary vestibular afferent activity. The aim of this study was to clarify the intrinsic characteristics of serotonin (5-hydroxytryptamine, 5-HT) release in the MVN during the period of vertigo induced by caloric stimulation.</p><p><b>METHODS</b>We used an in vivo microdialysis technique to examine the effects of caloric stimulation on the serotoninergic system in MVN. Twenty four guinea pigs were randomly divided into the groups of irrigation of the ear canal with hot water (n = 6), ice water (n = 6) and 37 degrees C water (n = 4), and the groups of irrigation of the auricle with hot water (n = 4) and ice water (n = 4), according to different caloric vestibular stimulation. We examined the animal's caloric nystagmus with a two-channel electronystagmographic recorder (ENG), and meanwhile examine serotonin (5-hydroxytryptamine, 5-HT) level in the MVN with microdialysis technique after caloric stimulation.</p><p><b>RESULTS</b>In the caloric test the hot water (44 degrees C) irrigation of the right external auditory canal induced horizontal nystagmus towards the right side lasting about 60 seconds and the ice water irrigation of the right external auditory canal induced it towards the left side lasting for about 90 seconds. No nystagmus was induced by 37 degrees C water irrigation of the external ear canal. Therefore, it was used as a negative control stimulation to the middle ear. The MVN 5-HT levels significantly increased in the first 5-minute collecting interval and increased to 254% and 189% of the control group in the second collecting interval in response to caloric vestibular stimulation with ice water and hot water respectively. The serotonin release was not distinctly changed by the irrigation of the auricle with ice water or hot water.</p><p><b>CONCLUSIONS</b>Neither somato-sensory stimulation of the middle ear nor nonspecific cold or hot stress affects the serotonin release. The rise of 5-HT in MVN may be involved in the mechanism of vertigo induced by caloric stimulation.</p>

Inhibition of salicylate on potassium channels in rat inferior colliculus neurons / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To understand what role of the transient outward potassium channels and the delayed rectifier potassium channels play in the mechanism of salicylate-induced tinnitus.</p><p><b>METHODS</b>The effects of salicylate on the transient outward potassium channels and the delayed rectifier potassium channels in freshly dissociated inferior colliculus neurons of rats were studied, using the whole-cell voltage clamp method.</p><p><b>RESULTS</b>Salicylate blocked the transient outward potassium current (I(K(A and the delayed rectifier potassium current (I(K(DR in concentration-dependent manner (0.1-1 mmol/L). The IC50 values for the blocking action of salicylate on I(K(A)) and I(K(DR)) were 2.27 and 0.80 mmol/L, respectively. At a concentration of 1 mmol/L, salicylate did not shift the activation and inactivation curves of I(K(A)), but significantly shifted the activation and inactivation curves of I(K(DR)) negatively by approximately 11 mV and 24 mV.</p><p><b>CONCLUSIONS</b>Salicylate inhibits both I(K(A)) and I(K(DR)) in rat inferior colliculus neurons but only significantly affects the activation and inactivation kinetics of I(K(DR)). Effects of I(K(A)) and I(K(DR)), especially I(K(DR)), by salicylate may play an important role in salicylate-induced tinnitus.</p>