Local administration of mononuclear cell, platelet-rich plasma and zoledronic acid for the prevention and treatment of early femoral head osteonecrosis and collapse: study / 中国组织工程研究

BACKGROUND: There are various treatment methods for osteonecrosis of the femoral head (ONFH) and collapse, but conservative treatment is invalid. Once femoral head collapse occurs, the development is irreversible. Our previous research has shown that local administration of zoledronic acid can prevent necrotic femoral head collapse. Moreover, bone marrow mononuclear cells obtain satisfactory short-term efficacy in the treatment of ONFH. OBJECTIVE: To investigate the curative efficacy of local administration of mononuclear cell, platelet-rich plasma and zoledronic acid for the prevention and treatment of early ONFH and collapse. METHODS: This prospective, single-center, randomized, parallel, controlled clinical trial was conducted at the Chinese PLA General Hospital, Beijing, China. One hundred patients with ONFH (stages I-II by Ficat and Arlet classification) were enrolled and randomly assigned into either the treatment group or control group (n=50 per group). Patients were given an injection of mononuclear cell, platelet-rich plasma and zoledronic acid into the necrotic femoral head, or drilling decompression at the necrotic area. Patients in both groups were then followed up for 4, 8, 12, and 18 months. The primary outcome measures were the blood supply, osteogenesis and appearance of the necrotic femoral head observed on hip perfusion by dynamic MRI, CT restruction of the hip joint and radiography of the hip joint, as well as Harris hip scores and numerical rating scale scores. Secondary outcome measures included SF-36 Health Survey and Activities of Daily Living scores. DISCUSSION: The outcomes of this trial have provided quantitative data for analyzing the effectiveness of local administration of mononuclear cell, platelet-rich plasma and zoledronic acid on ONFH and collapse. Written approval for this protocol was obtained from the Ethics Committee of the Chinese PLA General Hospital in China (approval No. S2015-082-01). Participants and their families are informed of the study protocol and procedures, and signed an informed consent. The study was in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. Trial began in January 2015 and will be completed in December 2017. Trial results will be published in scientific reports, or in peer-reviewed journals. This trial was registered with the ClinicalTrials.gov identifier: NCT02721940. Patient recruitment is ongoing.

Role of ubiquitin E3 ligase TRIM10 in regulating cardiomyocyte hyper-trophy / 中国病理生理杂志

AIM:To explore the role of ubiquitin E3 ligase tripartite motif 10 (TRIM10) in the development of cardiomyocyte hypertrophy .METHODS: Primary cultured neonatal rat cardiomyocytes ( NRCMs ) were infected with siRNA-TRIM10, siRNA-control, Ad-TRIM10 or Ad-GFP for 24 h respectively, and then stimulated with phenylephrine ( PE) for additional 24 h.The protein levels of TRIM10, AKT and ERK1/2 were determined by Western blot .The size of the NRCMs was measured by immunofluorescence staining .The mRNA expression of atrial natriuretic peptide ( ANP) and brain natriuretic peptide ( BNP) was detected by RT-qPCR.RESULTS:Compared with the control , PE treatment signifi-cantly increased the protein expression of TRIM 10.Moreover, transfection of NRCMs with siRNA-TRIM10 markedly inhibi-ted cardiomyocyte size , the mRNA expression of ANP and BNP , and the phosphorylation levels of AKT and ERK as com-pared with siRNA-control after PE treatment.In contrast, overexpression of TRIM10 significantly enhanced PE-induced hy-pertrophic effect on NRCMs above .CONCLUSION:TRIM10 regulates cardiomyocyte hypertrophy partially through AKT and ERK signaling pathways .

Role of ubiquitin E3 ligase TRIM10 in regulating cardiomyocyte hyper-trophy / 中国病理生理杂志

AIM:To explore the role of ubiquitin E3 ligase tripartite motif 10 (TRIM10) in the development of cardiomyocyte hypertrophy .METHODS: Primary cultured neonatal rat cardiomyocytes ( NRCMs ) were infected with siRNA-TRIM10, siRNA-control, Ad-TRIM10 or Ad-GFP for 24 h respectively, and then stimulated with phenylephrine ( PE) for additional 24 h.The protein levels of TRIM10, AKT and ERK1/2 were determined by Western blot .The size of the NRCMs was measured by immunofluorescence staining .The mRNA expression of atrial natriuretic peptide ( ANP) and brain natriuretic peptide ( BNP) was detected by RT-qPCR.RESULTS:Compared with the control , PE treatment signifi-cantly increased the protein expression of TRIM 10.Moreover, transfection of NRCMs with siRNA-TRIM10 markedly inhibi-ted cardiomyocyte size , the mRNA expression of ANP and BNP , and the phosphorylation levels of AKT and ERK as com-pared with siRNA-control after PE treatment.In contrast, overexpression of TRIM10 significantly enhanced PE-induced hy-pertrophic effect on NRCMs above .CONCLUSION:TRIM10 regulates cardiomyocyte hypertrophy partially through AKT and ERK signaling pathways .

Effect of diphenylhydantoin sodium polybutylcyanoacrylate nanoparticles on rat models of epilepsy / 中华神经医学杂志

Objective To evaluate the effects of diphenylhydantoin sodiumpolybutylcyanoacrylate nanoparticles (DPH-PBCA-NPs) and DPH-PBCA-NPs modified with Tween-80on rat models of epilepsy, and investigate the advantage of nanoparticle as the drug delivery system.Methods The rat models of acute epilepsy induced by lithium pilocarpine were established and randomly divided into 5 groups: group Ⅰ (performing injection of DPH-PBCA-NPs modified with Tween-80), group Ⅱ (performing injection of DPH-PBCA-NPs), group Ⅲ (performing injection of diphenylhydantoin sodium), group Ⅳ (performing injection of PBCA-NPs) and group Ⅴ (performing injection of physiological saline). The changes of electroencephalogram (EEG) manifestations of these rats were observed by using video-EEG monitoring; and their behavioral changes were noted too.Results The lithium pilocarpine induced rat models of acute epilepsy were successfully established and their status epilepticus were confirmed by EEG and their behaviors. The effective rate of DPH-PBCA-NPs modified with Tween-80 and DPH-PBCA-NPs was 91.67% and 54.55%, respectively;the effective rate of rats in group Ⅲ was 50%, and the effective rate of rats in group Ⅳ and Ⅴ was 0%;DPH-PBCA-NPs modified with Tween-80 enjoyed a better effect than DPH-PBCA-NPs and DPH (P＜0.05). Conclusion DPH-PBCA-NPs and DPH-PBCA-NPs modified with Tween-80 can be used to improve the behaviors of rats with acute epilepsy and modify the results of EEG of these rats.Nanoparticles as drug delivery system can help the drugs having their effects much quickly and effectively.

Clinical significance of 5-HT and DA levels in serum and cerebrospinal fluid of the patients with delayed encephalopathy after acute carbon monoxide poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the changes and the clinical significance of 5-hydroxytryptamine (5-HT), dopamine (DA) levels in serum and cerebrospinal fluid (CSF) of patients with delayed encephalopathy (DEACMP) after acute carbon monoxide poisoning.</p><p><b>METHODS</b>The dynamic detection of 5-HT and DA levels in serum and CSF from 42 patients with DEACMP was performed with high performance liquid chromatography (HPLC). The condition changes of patients with DEACMP were analyzed with three types of scales: the activity of daily living scale (ADL), information memory concentration test (IMCT) and Hasegawa's dementia scale (HDS); these changes were compared with those from 38 other encephalopathy patients and 38 non-encephalopathy patients, respectively.</p><p><b>RESULTS</b>Before treatment, the serum 5-HT and DA levels [(662.61 ± 178.50) and (155.74 ± 60.32) nmol/L, respectively] of DEACMP group were both significantly lower than those [(914.08 ± 198.04) and (225.70 ± 48.53) nmol/L] of non-encephalopathy group (P < 0.05); the serum DA level of DEACMP group was also significantly lower than that [(243.57 ± 66.94) nmol/L] of other encephalopathy group (P < 0.05); the serum 5-HT level of DEACMP group was not significantly different from that [(729.54 ± 299.87) nmol/L] of other encephalopathy group (P > 0.05). After treatment, the serum 5-HT and DA levels [(714.08 ± 170.47) and (192.18 ± 33.07 nmol/L, respectively)] of DEACMP group elevated to various extent, but only serum DA level was significantly higher than that before treatment (P < 0.05). Before treatment, the CSF 5-HT and DA levels of DEACMP group were significantly lower than those of non-encephalopathy group and those of other encephalopathy group (P < 0.05). After treatment, the CSF 5-HT level (232.44 ± 54.28 nmol/L) was similar to normal level and significantly higher than that before treatment (P < 0.05); the CSF DA level [(56.83 ± 12.85) nmol/L] of DEACMP group increased only slightly (P > 0.05). In DEACMP group, ADL score (50.64 ± 7.23), HDS score (8.55 ± 8.08) and IMCT score (4.95 ± 7.30) before treatment were significantly different from those (8.5 ± 8.08, 4.95 ± 7.30 and 15.64 ± 10.90) after treatment (P < 0.01). In DEACMP group, there wasa negative correlation between DA level changes and HDS score changes, when the DA levels and HDS scores before treatment were compared with those after treatment (P < 0.05).</p><p><b>CONCLUSION</b>The dynamic changes of 5-HT and DA levels in serum and CSF of patients with DEACMP consisted basically with the patient's condition change. The dynamically detected 5-HT and DA levels can be used as the biological indicators to reflect the condition change and treatment effects of DEACMP patients.</p>

Serum levels of endothelin-1, tumor necrosis factor-α and its clinical significance in patients with delayed encephalopathy after acute carbon monoxide poisoning / 中华神经医学杂志

Objective To investigate the serum levels of endothelin-1 (ET-1), tumor necrosis factor- α (TNF-α) and their dynamic changes in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) and their relation with the condition variation of the patients.Methods The serum ET-1 and TNF-α levels were determined with enzyme-linked immunno-sorbent assay (ELISA) in 31 patients with DEACMP, and the dynamic changes of patients' condition were monitored by use of the activity of daily living (ADL) scale, the information-memory-concentration test (IMCT) and the Hasegawa's dementia scale (HDS). The comparisons between patients with DEACMP and both 30 patients with acute carbon momoxide poisoning (ACMP) but without DEACMP and 30 normal controls were also conducted. Results At the acute stage of the DEACMP group, the serum levels of ET-1 and TNF-α were both significantly higher than those in the normal control group (P＜0.05); that of TNF-α was significantly lower than that in the ACMP group (P＜0.05), but that of ET-1 was not significantly different from that in the ACMP group (P＞0.05). The serum levels of ET-1 and TNF- α in the ACMP group were both significantly higher than those in the normal control group(P＜0.05). In the DEACMP group, the serum level of ET-1 at the convalescent stage was significantly lower than that at the acute stage (P＜0.05), but the serum level of TNF-α was not significantly different from that at the acute stage (P＞0.05). At the acute stage of the DEACMP group, ADL scores were significantly higher than those in norms, and IMCT scores and HDS scores were significantly lower than those in norms (P＜0.05). In the DEACMP group, the ADL scores at the convalescent stage were significantly lower than those at the acute stage (P＜0.05), IMCT scores and HDS scores were significantly higher than those at the acute stage (P＜0.05). Significant correlations between scores of any 2 of 3 scales in patients with DEACMP at both acute and convalescent stage were noted (P＜0.05). Conclusion The dynamic detection of serum ET-1 and TNF-α level variations could be used as an indicator for condition severity in patients with DEACMP.

Changes of Cognitive Function before and after Magnesium Valproate Sustained Release Tablets Treatment on Epileptic Children / 实用儿科临床杂志

Objective To observe the effect of magnesium valproate sustained release tablets on children with epilepsy and its effects on cognitive function.Methods Magnesium valproate sustained release tablets were conducted on 38 cases.Close attention was paid to both the degree of paroxysm control and side effects during treatment while periodic examinations on liver function and blood routine were also conducted.The intelligence and P300 of children with epileptics were respectively measured before and after 6-month treatment.Forty children of control group was set up.Results Eighteen cases were totally under controlled(47.4%),11 obviously effect(28.9%),6 effect(15.8%).The total effective rate in total was 92.1%.Obvious differencees in intelligence between children with epileptics and control group before and after 6-month treatment were observed(all P0.05).Conclusions Magnesium valproate sustained release tablets is a new type of broad-spectrum anti-epileptic drug,which has an obvious effect on treatment of children with epileptic without any obvious adverse reaction.It imposes little influence on children′s cognitive function.