BACKGROUND: Studies are very few regarding the specific reaction of bone marrow mesenchymal stem cells (BMSCs) to activated microglia. Moreover, it remains unclear how MSCs maintain dopaminergic neuronal survival under specific microenvironment.OBJECTIVE: To explore the effect of BMSCs stimulated by activated microglia on dopaminergic neuron survival.METHODS: BMSCs were isolated from Wistar rats by attachment method, and in vitro cultured; microglia was activated, and dopaminergic neurons were cultured by enzyme digestion method. The experiment included 5 groups: BMSCs, microglia, lipopolysaccharide (LPS)+microglia; BMSCs+LPS+microglia groups, in which the dopaminergic neurons were cultured with corresponding culture medium; the dopaminergic neurons alone group was cultured with 10% fetal bovine serum+ DMEM/F12. The effect of different microenvironment on dopaminergic neuron survival and gliocyte-derived neurotrophic factor released from BMSCs were detected by immunofluorescence technique.RESULTS AND CONCLUSION: The release of gliocyte-derived neurotrophic factor in groups involving BMSCs was greater than corresponding control group. Tyrosine hydroxylase immunofluorescence showed that neuronal survival of dopaminergic neurons alone group was 15%, microglia group was 10%, LPS+microglia was 5%, but BMSCs+LPS+microglia group was 28%, significantly greater than the other groups (P < 0.05). In addition, survival of in vitro cultured dopaminergic neurons was decreased with increasing culture duration, but the survival of dopaminergic neurons in group involving BMSCs was significantly greater than corresponding control group. This indicates that microglia activation stimulated BMSCs to upregulate gliocyte-derived neurotrophic factor to prevent dopaminergic neurons from toxic injury, and inhibit delayed death of dopaminergic neurons.

OBJECTIVETo investigate the significance of beta-adrenergic receptor 2 (beta2-AR) and vascular endothelial growth factor-2 (VEGFR-2) in the occurrence and development of infantile hemangioma through detecting the expression of beta2-AR and VEGFR-2 in the different stages of infantile hemangiomas.

METHODSAccording to the Mulliken's classification standard, we classified the specimens as proliferating group (32 cases), involuting group (17 cases) and involuted group (11 cases). Normal skin tissue surrounding the hemangioma from 7 cases were chosen as control group. The expression of beta2-AR and VEGFR-2 was detected by immunohistochemical technique in proliferating hemangioma, involuting hemangioma, involuted hemangioma. The mean optical density was measured by image analysis system (Image Pro Plus 6.0) and SPSS 16.0 software was applied for statistical analysis.

RESULTSThe expression of beta2-AR and VEGFR-2 was strongly positive in proliferating hemangioma, while positive in involuting hemangioma and weakly positive in the involuted stage. The mean optical density of each phase was 0.064 751 2 +/- 0.012 747, 0.031 6017 +/- 0.006 848,0.011 869 8 +/- 0.039 349 for beta2-AR, and 0.068 940 9 +/- 0.029 274, 0.028 445 5 +/- 0.006 396, 0.011 184 1 +/- 0.004 198 for VEGFR-2. The differences between different stages had a statistically significance (P < 0.05). Correlation analysis on the mean optical density between beta2-AR and VEGFR-2 had a statistically significance (P < 0. 05).

CONCLUSIONSBeta2-AR and VEGFR-2 may be involved in the occurrence and development of infantile hemangioma.

Child ; Child, Preschool ; Female ; Hemangioma ; metabolism ; Humans ; Infant ; Male ; Receptors, Adrenergic, beta-2 ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; metabolism

Today, the understanding of the sequence and structure of biologically relevant targets is growing rapidly and researchers from many disciplines, physics and computational science in particular, are making significant contributions to modern biology and drug discovery. However, it remains challenging to rationally design small molecular ligands with desired biological characteristics based on the structural information of the drug targets, which demands more accurate calculation of ligand binding free-energy. With the rapid advances in computer power and extensive efforts in algorithm development, physics-based computational chemistry approaches have played more important roles in structure-based drug design. Here we reviewed the newly developed computational chemistry methods in structure-based drug design as well as the elegant applications, including binding-site druggability assessment, large scale virtual screening of chemical database, and lead compound optimization. Importantly, here we address the current bottlenecks and propose practical solutions.

Objective To explore the effectiveness and precision of 3D printing navigational template in puncturing of foramen rotundum for radiofrequency thermocoagulation to treat primary trigeminal neuralgia (V2).Methods Forty-three patients (27 males,16 females,aged 45-85 years,ASA grade Ⅰ or Ⅱ) with primary trigeminal neuralgia (V2) were included and randomly divided into experimental group (group A,n=21) and control group (group B,n=22).After taking a CT scan and 3D reconstruction of each patient's skull,puncture simulations were carried out,then the final puncture schemes were decided.In group A,puncture was performed under guidance of navigational template but was conducted empirically in group B.In both groups,3D-CT image and electrical stimulation were used in all the procedures to confirm the location of point of needle before radiofrequency thermocoagulation.The cases of successful puncture in one-time,times of CT scanning,radiant quantity,operation time during the operation in both groups were recorded.Furthermore,NRS scores and complications including hypoesthesia,motor function degeneration,hematoma,absence of corneal reflex,cerebrospinal fluid leakage were recorded after procedure.Results The rate of successful puncture in one-time of group A was superior than that of group B (90.4% vs.22.7%).Compared with group B,CT scan times [(1.1±0.3) times vs.(2.8±1.3) times],radiant quantity [(323.1±108.7) mGy*cm vs.(787.8±355.7) mGy*cm],operation time [(15.3±5.5) min vs.(28.5±6.5) min] in group A were significantly reduced (P<0.05).NRS scores of both two groups were obviously reduced after surgery [group A: (3.1±1.7) scores vs.(8.5±0.7) scores;group B: (3.1±1.5)scores vs.(8.5±0.7) scores] (P<0.05),but the effectiveness in group A was not superior than group B.No serious complications occurred in all patients.Conclusion On the basis of sufficient preoperative planning of puncture approach,3D printing template can significantly enhance the effectiveness and precision of puncture of foramen rotundum,improving the efficiency and quality of radiofrequency treatment of primary trigeminal neuralgia (V2).

Objective To investigate the efficacy and safety of lauromacrogol foam sclerosant in the treatment of peripheral venous malformations.Methods 21 patients with peripheral venous malformations were treated with foam sclerotherapy.The sclerosing foam was produced by Tessari's method using 1％ lauromacrogol.When necessary,the injections were repeated at an interval of four weeks,and this process contained 3 to 5 injections.Therapeutic outcomes and safety were established by evaluating size of lesion,symptom,duration of treatment and side-effects of treatment before and after treatment.Results 21 patients were followed up for 3 to 18 months.10 cases showed markedly shrinked or even disappeared of treated malformations,9 cases showed a reduction in size over 50 ％,and 2 cases showed a reduction in size less 50 ％.Local swelling occurred in almost per session,pyrexia in 5 patients,which resolved spontaneously within several days to 1 week.No major complication occurred.Conclusions Foam sclerotherapy using lauromacrogol seems to be a safe and effective therapeutic method for peripheral venous malformations.

Objective To prepare a kind of superparamagnetic iron oxide (SPIO) and doxorubicin loaded multifunctional polymer microbubbles (MPMBs),and to explore its potential application as an ultrasound(US)/magnetic resonance (MR) imaging contrast agent in vitro.Methods The MPMBs and normal polymer microbubbles (PMBs) were made by double emulsion and freeze-drying methods.The physical property,drug encapsulation efficiency and the drug-loading efficiency of MPMBs were determined,and the release property and US/MR imaging enhancement of MPMBs were observed.Results The MPMBs had a regular shape and narrow size distribution.The drug encapsulation efficiency was (60.20±2.69) ％,and the drug-loading efficiency was (6.02 ± 0.27) ％.The in vitro release experiment showed that ultrasound can promote the release of doxorubicin in MPMBs.US imaging in vitro showed that the enhancement of MPMBs was better than PMBs,and MR imaging in vitro conformed that MPMBs could well enhance MR imaging.Conclusions The MPMBs is a multifunctional contrast agent with the treatment function as well as US/MR dual-mode imaging enhancement effect.

Objective To prepare polyclactic-co-glycolic acid(PLGA) polymer ultrasound contrast agent loading sudan black dye (SB-PLGA) and study the enhancement effect of it on rabbit lymph nodes imaging and as a sentinel lymph node (SLN) biopsy in the feasibility and value of the indicator.Methods SB-PLGA ultrasound contrast agent was made by double emulsion and freeze-drying methods.Thigh subcutaneous rabbit VX2 tumor model of eight lymph nodes were set up with the foot pad subcutaneous injection of contrast agents to get contrast-enhanced ultrasound imaging of the popliteal lymph node and the second inguinal lymph node stations.Then the blue stained lymph nodes were resected by popliteal lymph node dissection and the second station lymph nodes were also observed after 30 mins respectively,lymph nodes were examined by frozen sections HE staining in parallel.Results SB-PLGA microbubbles had a tight size distribution.Ultrasound imaging can be significantly enhanced lymph node imaging,the second station lymph node imaging was not obvious.Popliteal lymph node dissection for lymph node staining,30minutes later,frozen sections HE staining were seen within the lymph node contrast agent present in the lymphatic sinus and a large entry of macrophages.Inguinal lymph node dissection showed the second station of lymph nodes no blue staining.Conclusions SB-PLGA ultrasound contrast agent is good for sentinel lymph node imaging and biopsy indicator.Contrast agent retention and accumulation in the lymph nodes by the uptake of macrophages may be associated with the mechanisms of lymph node enhanced imaging.

Objective:To establish a preliminary diagnostic criteria of pathological internet use for field test in China.Methods:Through searching common "pathological internet use" diagnostic criteria or screen criteria in literature,a diagnostic criteria items pool and a preliminary diagnostic criteria of "pathological internet use" were established .According to the diagnostic criteria,each 2 senior professional psychiatrists in turn interviewed 79 patients and their parents,and then made diagnosis respectively. In addiction,44 high school students were each evaluated by one psychiatrist.The definite diagnosis was made when 2 evaluators make the same diagnosis for one patient.Result:In 123 patients,54 were pathological internet use.For diagnosis,the value of kappa for inter-rater reliability was 0.812( P<0.001).In the 12 criteria items,2 for poor inter-rater reliability and 4 for little contribution to diagnosis were eliminated.In the reserved 6 items,if 4 items(or more)were positive,the diagnostic sensitivity was 78.9% and specificity was 95.3%.Functional impairment criteria were made strictly.In the patients who were made the definite diagnosis,90.7% had duration of illness above 3 months,and 77.7% above 6 months.Conclusion:The preliminary diagnostic criteria of pathological internet use after revised includes 6 symptom criteria,3 functional impairment criteria,duration of illness and exclusive criteria.The criteria proposed is with high consistency on evaluations made by psychiatric raters,and with operational convenience.The criteria,after further revised,may fit the clinical application.

Objective To compare the clinical effect and safety of limited fluid resuscitation and aggressive/normotensive fluid resuscitation in treatment of earthquake-induced traumatic hemorrhagic shock patients so as to provide reference for clinical application.Methods A total of 62 patients with traumatic hemorrhagic shock in earthquake were employed and divided randomly into limited fluid resuscitation group(Group Ⅰ,30 patients)and aggressive/normotensive fluid resuscitation group(Group Ⅱ,32 patients).All the patients were resuscitated by using halanted solution and HAES-steril as resuscitanaid resuscitation.Then,surgical hemostasis was carried out and dynamic changes of mean blood pressure(MAP),heart rate and central venous pressure(CVP)observed.The base excess,lactic acid and creatinine were detected at four resuscitation points.Results Before full fluid resuscitation,MAP remained at 50-70 mm Hg and 70-90 mm Hg respectively in both groups.After early resuscitation.heart rate showed significant decrease,while CVP increased(P＜0.01)but still changed at normal range.Total transfusion volume in Group Ⅰ was less than that of GroupⅡ(P＜0.01).There was no statistical difference upon urine volume(P＞0.05).There was statistical difierence upon base excess value after resuscitation within group(P＜0.01)but no statistical difference between two groups(P＞0.05).After resuscitation,hetic acid level wag obviously reduced in both groups(P＜0.01),with more significant change in Group Ⅰ,with statistical difference compared with Group Ⅱ(P＜0.01).There showed a significant decrease of creatinine in both groups after resuscitation.with statistical difierence within group (P＜0.01)but without statistical difference between two groups(P＞0.05).Conclusions Compared with aggressive/normotensive fluid resuscitation,limited fluid resuscitation is a more safe and effective way for fluid resuscitation of traumatic hemorrhagic shock,for it can not only reduce transfusion volume and ameliorate hemodynamic indices,but also can increase oxygen supply,improve microcirculation and protect renal function.

Objective To assess the effectiveness and safety of propranolol in infantile hemangiomas by comparing with prednisone.Methods A systematic literature search of PubMed,Embase,Cochrane,Ovid,Google Scholar and CNKI,VIP,Wanfang database was conducted to identify studies about the treatment of propranolol in children with hemangiomas.We chose randomized controlled trials and clinical controlled trials.We selected literatures by certain standards.Results Eight papers including 9 studies were identified by the strategy mentioned above.These 8 literatures met our inclusion criteria after review by two independent reviewers.The studies comprised 407 patients.Six of the control group were oral prednisone,and there was no statistic heterogeneity (P =0.09,I2 =0％).The fixed model was used to do the statistic analysis.The outcome showed the effective rate of propranolol was higher than that of prednisone,with statistically significant difference (OR=7.56,95％ CI:3.18-17.98).Three of the control group included observation or oral placebo,without statistic heterogeneity (P=0.48,I2=0％) either.The outcome showed the effective rate of propranolol on hemangioma was higher than that of the control group (OR=23.15,95％CI:7.15-74.94).Of all the eight researches,five reported adverse effects,with statistic heterogeneity (P=0.0003,I2 =81 ％).In addition,the adverse rate of propranolol was lower than that of prednisone,with statistically significant difference (OR=0.12,95％ CI:0.02-0.75).Conclusions The results of this meta-analysis show that oral propranolol could obviously decrease the volume and improve the color of infantile hemangiomas.And propranolol is a significantly more effective for IH than steroids.The incidence of adverse effects of propranolol is also lower than that of prednisone.As a result,propranolol should be recommended as the first choice therapy for infantile hemangioma.