Objective To investigate the value of measurement of cardiac output in children by bio-reactance versus echocardiography.Methods Pediatric patients admitted in pediatric department of Peking University First Hospital from September to December 2012 who needed hemodynamic monitoring were enrolled prospectively.Cardiac index(CI)and stroke volume(SV)were measured by echocardiography and non-invasive cardiac output measurement(NICOM)and compared by Spearman correlation and Bland-Alt-man analysis.Results Thirty patients were included.The median age was 7.25 years.CI[M(P5 ,P95 )] measured by NICOM and echocardiography were correlated significantly[3.42(2.28,4.92)L /(min?m2 ) vs.3.51 (2.94,4.85 )L/(min?m2 ),R =0.385,P =0.035 ].Bland-Altman analysis revealed a bias of-0.22 L/(min?m2 )(P =0.051 ),limits of agreement of -1.40 to 0.95 L/(min?m2 ).SV[M(P5 ,P95 )] measured by NICOM and echocardiography were correlated more significantly [36.3 (12.6,87.8 )ml vs.39.4(14.7,86.9)ml,R =0.768,P ﹤0.001 ].Bland-Altman analysis revealed a bias of -3.1 ml(P =0.176),limits of agreement of -27.4 to 21.2 ml.Conclusion There is no significant difference between NICOM and echocardiography for the measurement of CI and SV in pediatric patients.Further validation studies need to be conducted before routine clinical use.

Neurite outgrowth, a cell differentiation process involving membrane morphological changes, is critical for neuronal network and development. The membrane lipid, phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), is a key regulator of many important cell surface events of membrane signaling, trafficking and dynamics. This lipid is produced mainly by the type I PI 4-phosphate 5-kinase (PIP5K) family members. In this study, we addressed whether PIP5Kalpha, an isoform of PIP5K, could have a role in neurite outgrowth induced by nerve growth factor (NGF). For this purpose, we knocked down PIP5Kalpha in PC12 rat pheochromocytoma cells by stable expression of PIP5Kalpha microRNA that significantly reduced PIP5Kalpha expression and PIP2 level. Interestingly, NGF-induced neurite outgrowth was more prominent in PIP5Kalpha-knockdown (KD) cells than in control cells. Conversely, add-back of PIP5Kalpha into PIP5Kalpha KD cells abrogated the effect of NGF on neurite outgrowth. NGF treatment activated PI 3-kinase (PI3K)/Akt pathway, which seemed to be associated with reactive oxygen species generation. Similar to the changes in neurite outgrowth, the PI3K/Akt activation by NGF was potentiated by PIP5Kalpha KD, but was attenuated by the reintroduction of PIP5Kalpha. Moreover, exogenously applied PIP2 to PIP5Kalpha KD cells also suppressed Akt activation by NGF. Together, our results suggest that PIP5Kalpha acts as a negative regulator of NGF-induced neurite outgrowth by inhibiting PI3K/Akt signaling pathway in PC12 cells.
Animals ; Enzyme Activation/drug effects ; Gene Knockdown Techniques ; Mice ; Nerve Growth Factor/*pharmacology ; Neurites/drug effects/*enzymology ; PC12 Cells ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phosphorylation/drug effects ; Phosphotransferases (Alcohol Group Acceptor)/*metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects

[ ABSTRACT] AIM:To investigate the effect of oxidized low-density lipoprotein ( ox-LDL) on autophagy in mac-rophages and the underlying molecular mechanisms.METHODS:RAW264.7 macrophages were pretreated with 2 mg/L anti-CD36 monoclonal antibody (anti-CD36 mAb), 5 μmol/L diphenyleneiodonium (DPI), 3 mmol/L 3-methyladenine (3-MA) or 1μmol/L rapamycin for 1 h and then treated with ox-LDL (100 mg/L) for 12 h.The viability of the cells was measured by MTT assay.The activities of lactic dehydrogenase ( LDH) in the medium and nicotinamide adenine dinucleoti-de phosphate ( NADPH) oxidase, superoxide dismutase ( SOD) in the cells as well as the levels of intracellular reactive ox-ygen species ( ROS) and malondialdehyde ( MDA) were determined to characterize the membrane integrity and the oxida-tive stress, respectively.The protein levels of beclin-1 and microtubule-associated protein 1 light chain 3-II ( LC3-II) , 2 important molecular markers of autophagy, were examined by Western blotting.RESULTS:ox-LDL induced autophagy in
RAW264.7 macrophages as assessed by upregulation of beclin-1 and LC3-II.Similar to 3-MA, an autophagy inhibitor, an-ti-CD36 mAb significantly inhibited the ox-LDL-induced upregulation of beclin-1 and LC3-II.Anti-CD36 mAb suppressed the ox-LDL-induced oxidative stress as revealed by decreased NADPH oxidase activation, ROS and MDA generation as well as increased SOD activity.Similar results were observed in the cells pretreated with DPI, a NADPH oxidase inhibitor.Mo-reover, DPI significantly inhibited the ox-LDL-induced upregulation of beclin-1 and LC3-II.Inaddition, the decrease in the cell viability and increase in LDH release induced by ox-LDL were promoted by 3-MA and blocked by rapamycin ( an auto-phagy inducer).CONCLUSION: ox-LDL induces autophagy in RAW264.7 macrophages, which may be involved in CD36-mediated ox-LDL uptake and subsequent activation of oxidative stress, and moderate activation of autophagy may pro-tect macrophages from ox-LDL-induced injury.

With the promotion of precision medicine , tumor targeted therapy has entered into a new stage .Developments in molecular biotechnology have contributed to the discovery of numerous novel molecular targets .The advent of new targeted drugs and continuous updating data from large clinical research have provided more options for the precise treatments of lung cancer .This article aims to review the latest progress about targeted therapy and precision medicine in lung cancer .

Objective To observe the effect of mechanical horseback riding on balance ability in stroke patient. Methods 40 stroke patients were divided into 2 groups. Treatment group was treated with mechanical horseback riding exercise and routine rehabilitation therapy, while control group was treated with the routine therapy only. They were assessed with the flat pressure test system and the Berg balance scale before and 10 weeks after the treatment. Results Comparing with control group, the whole path length and the unit path length when opening eyes decreased in treatment group （P<0.05）. Conclusion Mechanical horseback riding could improve the balance ability in stroke patients.

Objective To discuss therapeutic effect of mechanical horseback riding on the activities of daily living in the elderly stroke patient.Methods 47 stroke patients were randomly divided into two groups: Treatment group was treated with mechanical horseback riding exercise and routine traditional treatment, while control group was treated the traditional treatment only. 8 weeks after treatment, the degree of activity of daily living and motor function were assessed with the modified Barthel Index and the Fugl-Meyer Motor Scale respectively before and after the treatment.Results Comparing with control group, the score of FMA and modified Barthel index in horseback riding group were higher significantly(P<0.05).Conclusion Mechanical horseback riding could enhance the activity of daily living of elder stroke patients.

Objective To investigate the long-term outcome of old stroke patients after rehabilitation. Methods 25 old hospitalized patients with first attack of stroke in recovery were followed up with Mini-mental Status Examination (MMSE), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), Brunnstrom stages of hemiplegia, modified Ashworth scale (MAS), range of motion (ROM) in hemiplegic ankle, manual muscle test (MMT) of quadriceps femoris, Berg balance scale (BBS), modified Barthel index (BI) and the Zarit burden interview (ZBI) for caregiver before rehabilitation, discharge, 6 and 12 months after discharge. Results The Brunnstrom stages of lower limbs, MAS of upper limbs improved (P<0.05) after 3-month rehabilitation in hospital, as well as the scores of BBS, BI and ZBI. As 6 and 12 months in home, the limb function remained stable, while the scores of BBS, MMSE, BI, SAS, and ZBI improved, but SDS fluctuated (P<0.05). Conclusion It is important to offer the long-term rehabilitation or consultation service when advocating old stroke patients early return to family or community, including psychological support and intervention.

OBJECTIVE: To detect the expression of c-myc in the tissue of laryngeal squamous cell carcinoma. RNA interference(RNAi) was employed to inhibit the expression of c-myc in Hep-2 cells and to evaluate the effects of c-myc as a target for gene therapy in laryngeal carcinoma. METHOD: Immunohistochemistry was used to determine the protein levels of c-myc and Rb in 80 cases of laryngeal squamous cell carcinoma and 30 cases of polyp of vocal cord. Hep-2 cells were transfected with c-myc siRNA, c-myc protein and mRNA levels were detected using Western Blotting and RT-PCR. Cell viability was detected by MTT after the Hep-2 cells were transfected with c-myc siRNA for different times or transfected with different concentrations c-myc siRNA. The sensitivity of Hep-2 cells to 5-Fu transfected with or without c-myc siRNA was evaluated also by MTT. Hep-2 cells were transfected with c-myc siRNA in combination with 5-Fu for 48 h and then analyzed cell apoptosis by flow cytometry. RESULT: Immunohistochemical analysis showed that c-myc was highly expressed in the tissues of laryngeal squamous cell carcinoma while the expression of Rb was lower. The protein and mRNA levels of c-myc decreased after transfected with c-myc siRNA. The results of MTT showed that the c-myc siRNA inhibited Hep-2 cells growth in a concentration-dependent manner. When transfected with c-myc siRNA(50 nmol/L), the cells were inhibited in a time-dependent manner. Compared with the untransfected cells, the viability of transfected Hep-2 cells was significantly suppressed at the same concentration of 5-Fu (P < 0.05). C-myc siRNA combination with 5-Fu could obviously increase cell apoptosis, even in the low concentration of 5-Fu (P < 0.05). CONCLUSION The protein level of C-myc has highly expressed in tumor tissues. C-myc siRNA can effectively inhibit the expression of c-myc and has anti-proliferation effects, increasing the sensitivity of Hep-2 cells to 5-Fu. Therefore,c-myc might be a good target for cancer treatment.
Adult ; Aged ; Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

Objective To study the influence of continuous blood purification(CBP) on cardiac out-put of pediatric patients using bioreactance. Methods Patients underwent CBP in PICU and nephrology ward from March 2014 were prospectively enrolled after approval by ethics committee. CBP therapies were all performed by Fresenius Medical Care hemodialysis machine. Cardiac output values were obtained using the non-invasive cardiac output monitoring ( NICOM) device ( Cheetah Medical). Blood pressure, heart rate, cardiac index(CI) and stroke volume index(SVI) were recorded before the therapy,at the beginning of ther-apy,during the course of therapy,and at the end of each therapy. Results Twenty-one pediatric patients (from 1. 0 year to 15. 5 years) were recruited and 69 treatments were recorded from March 2014 to Decem-ber 2016. The basic CI was 3. 4 (2. 4,6. 1) L/(min·m2),basic SVI was 43 (26,75) ml/(m2·beat). Dur-ing the beginning of therapy,mean arterial pressure(MAP),CI and SVI all dropped from the baseline ( P<0. 001),whereas heart rate increased. During the course of CBP,CI and SVI (were both recorded every 4 hours) kept on dropping and stayed at a relatively lower level. Course CI was 3. 0 (2. 4,4. 6) L/(min·m2) and course SVI was 28 (21,57) ml/(m2·beat). At the end of therapy,CI was 3. 4 (2. 5,5. 3) L/(min· m2),with no significant difference from the baseline CI (P＝0. 073). However,the SVI at the end of therapy was 35 (25,67) ml/(m2·beat),higher than the course SVI but still lower than the basic SVI,the differences were statistically significant ( P<0. 05). Conclusion CI and SVI continue to decline at the beginning of CBP treatment and remain at a lower level throughout the course of treatment. After the therapy, CI has returned to the basic level whereas SVI has not recovered.