Objective Combination of nanoparticle with p53 and Rb gene therapy by gene targeting was applied to investigate its curative effect and safety evaluation on colorectal rabbit hepatic VX2 metastasis for tumor eradication and survival enhancement. Methods Recombinant expressing plasmids harboring wild type p53 and Rb were cotransferred or transferred separately to the rabbit hepatic VX2 metastasis by the emulsion of PLL-nHAP nanoplex and lipodiol through the hepatic artery in a tumor target manner. Subsequent co-expressions of p53 and Rb protein within the treated tumors were detected by Western blot and in situ analysis of confocal laser scanning microscope. The therapeutic effect was evaluated by the tumor growth velocity and the survival time of animals. Eventually, investigations of liver function were applied to evaluate the safety of the process. Results With safe procedure for the rabbits liver function, both p53 and Rb local nano-therapy showed favorable anti-tumor effects and increased animal survival time. p53+Rb local nano-therapy could significantly inhibit hepatic VX2 metastasis and enhance the animal survival time compared with p53 local nano-therapy or Rb local nano-therapy. Local nano-therapy showed no significant influence to animal liver function. Conclusions Rb can work synergistically with p53 in the combined therapy mediated by PLL-nHAP nanoplex to augment the anti-tumor effect. The local nano-therapy with p53 and Rb is likely to be an effective and safe anti-tumor therapy for hepatic colorectal metastasis.

Metabonomics involves the unbiased quantitative and qualitative analysis of the complete set of metabolites present in cells, body fluids and tissues (the metabolome) based on modern analytic technique with high throughput, high sensitivity, and high resolution. Gas chromatography-mass spectrometry (GC-MS) is used to gain qualitative results of detected metabolites for biological samples as it provides superior distinguishability, detection sensitivity and integrated standard mass spectrometry library. In this article, the historic developments of GC-MS and its application in metabonomics in the past several years were reviewed. Firstly, the classification and the derivative methods of GC-MS were introduced. Subsequently, sample pretreatment process, qualitative and quantitative analysis and data analysis during detecting metabolites by GC-MS were introduced, then its application in microorganism, plant and disease diagnosis was systematically summarized. Finally, the problems in metabonomics study based on GC-MS and the research prospect in the future were discussed.
Gas Chromatography-Mass Spectrometry ; methods ; Metabolomics ; methods

OBJECTIVE: To investigate the feasibility of applying ultracision-harmonic scalpel in tonsillectomy. METHOD: Thirty-one cases treated with tonsillectomy which applied with nasal endoscope and ultracision-harmonic scalpel (ultrasonic scalpel group) and 31 cases treated with routine operation (routine group) respectively. The operating time and blood loss during operation and the degree of pain and the region of inflammation humidity as well as hospitalization days were observed. RESULT: All indexes in ultrasonic scalpel group were lower than that in the routine group, including operating time and blood loss during operation, and they were obviously difference in statistics (P < 0.01). CONCLUSION The application of ultracision-harmonic scalpel in tonsillectomy was safe, efficient and feasible, and would have a nice application prospect during ear-nose-throat operation.
Adolescent ; Adult ; Chronic Disease ; Endoscopy ; Female ; Hemostasis, Surgical ; methods ; Humans ; Male ; Nasal Cavity ; surgery ; Tonsillectomy ; instrumentation ; methods ; Tonsillitis ; surgery ; Treatment Outcome ; Ultrasonic Therapy ; instrumentation ; Young Adult

Objective To synthesize the antifungal tetrapetide by solid-phase synthesis method .Methods The solid-phase peptide synthesis was chosen for getting the desired target tetrapeptide and its structure was confirmed by MS and 1 H NMR.Results The synthesis of the D-Phe-Val-D-Val-Tyr-OH was realized with yield of 47%.Conclusion The synthetic method was feasible and practical.The desired target tetrapeptide could be used for screening of antifungal activity .

Objective:To construct a fall risk prediction model for patients with hematologic malignancies and to provide a reference for the risk assessment and accurate management of falls.Methods:The prospective study design was adopted to facilitate the selection of 510 patients with hematologic malignant in Qilu Hospital of Shandong University for investigation, and relevant data such as patient demographic characteristics, disease treatment and drugs were collected. The LASSO-Logistic regression was used to screen the risk factors of falls in patients with hematologic malignancies, to construct a nomogram risk prediction model. The receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the predictive performance of the model. Bootstrap resampling were used to validate internal validation of the model.Results:Among 510 patients with hematological malignancies, there were 273 males and 237 females, aged 53.0 (41.0, 63.0) years old. A total of 6 risk factors were included in the fall risk prediction model for patients with hematological malignancies, which were disease type ( OR = 0.185, 95% CI 0.061 - 0.562), body temperature ≥38 ℃ ( OR = 2.239, 95% CI 1.128 - 4.445), pain ( OR = 15.581, 95% CI 6.592 - 36.829), anemia ( OR = 4.097, 95% CI 1.536 - 10.927), days of bone marrow suppression ( OR = 3.341, 95% CI 1.619 - 6.893), and assessment of daily self-care ability ( OR = 3.160, 95% CI 1.051 - 9.506)(all P<0.05). The ROC curve of the fall risk prediction model was 0.884 (95% CI 0.841-0.927). The optimal threshold, sensitivity, and specificity of the risk prediction model were 0.248, 87.4% and 75.6%. The internal validation C statistic was 0.873. The Calibration curve was almost coincides with the ideal curve, and the model Brier score was 0.080. Conclusions:The constructed fall risk prediction model has good predictive performance, which can efficiently and objectively quantify the risk of falls, and provide a reference for the early assessment and effective prevention of falls in patients with hematological malignancies.

Objective:To analyze the application value of sakubatril valsartan in the treatment of chronic heart failure (CHF) based on cardiopulmonary test system.Methods:One hundred and thirty-five CHF patients admitted to the Affiliated Hospital of Jining Medical Collegefrom January 2019 to August 2020 were divided into the observation group (67 cases) and the control group (68cases) by random number table method. Both groups were treated with bisoprolol. The observation group was treated with the combination of sakubatril valsartan, and the control group was treated with the combination of benapril. The efficacy and cardiac function indicators of the two groups were compared. The cardiopulmonary exercise test system was used to measure the patient′s maximum exercise time (Tmax), maximum exercise Watt (Wmax), peak volume oxygen (Peak VO 2) and volume of anaerobic threshold oxygen (VO 2AT), and the incidence of adverse reactions were calculated. Results:The total effective rate in the observation group was higher than that in the control group: 92.54% (62/67) vs. 77.94%(53/68), the difference was statistically significant ( χ2 = 5.70, P<0.05). After the treatment, the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) in the observation group were lower than those in the control group: (2 000.47 ± 517.85) ng/L vs. (2 777.39 ± 812.49) ng/L, (0.33 ± 0.10) μg/L vs. (0.37 ± 0.09) μg/L, and the left ventricular ejection fraction (LVEF) was higher than that in the control group: (8.12 ± 6.44)% vs. (41.93 ± 6.73)%, the differences were statistically significant ( P<0.05). After the treatment, the left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), left ventricular mass index (LVMI), left atrial volume index (LAVI) in the observation group were lower than those in the control group: (55.47 ± 6.93) mm vs. (62.00 ± 7.18) mm, (37.14 ± 6.36) mm vs. (41.35 ± 6.43) mm, (136.76 ± 7.13) mg/m 2 vs. (140.98 ± 7.47) mg/m 2, (28.23 ± 2.59) ml/m 2 vs. (31.98 ± 2.17) ml/m 2; the Tmax, Wmax, PeakVO 2 and VO 2AT in the observation group were higher than those in the control group: (619.08 ± 65.36) s vs. (58.70 ± 52.44) s, (142.96 ± 16.05) W vs. (124.19 ± 13.38) W, (20.00 ± 5.74) ml/(min·kg) vs. (18.13 ± 3.58) ml/(min·kg), (13.89 ± 3.69) ml/(min·kg) vs. (11.23 ± 2.36) ml/(min·kg), the differences were statistically significant ( P<0.05). However, there was no statistically significant in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Sakubatril valsartan in the treatment of CHF can not only optimize the efficacy and improve cardiac function, but also benefit cardiac exercise rehabilitation of patients, and not increase the safety risk.

Objective:To compare the efficacy of sakubatril valsartan and valsartan in the treatment of patients with chronic cardiac insufficiency and the influence on zinc finger protein A20 and nuclear factor-κB (NF-κB) in peripheral bloodmononuclear cells (PBMCs).Methods:Ninety-senven patients with chronic cardiac insufficiency admitted to the Affiliated Hospital of Jining Medical College from February 2019 to January 2020 were continuously selected and randomly divided into the control group (48 cases) and the observation group (49 cases). Both groups received routine anti-heart failure according to the guidelines. The control group added with valsartan and the observation group added with sakubatril valsartan treatment. Before the treatment and after 3 months of treatment, the changes of cardiac function indexes and the changes of inflammatory markers such as hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP-9), and N-terminal pro B-type natriuretic peptide (NT-proBNP) were compared. PBMCs was extracted to detect zinc finger protein A20 and NF-κB levels. The incidence of adverse reactions in the two groups was recorded, and the relationship between zinc finger proteins A20, NF-κB and the myocardial injury marker NT-proBNP were analyzed.Results:After 3 months of treatment, the changes of cardiac function indexes in the observation group were better than those in the control group and the levels of hs-CRP, TNF-α, MMP-9, NT-proBNP in the observation group were lower than those in the control group: (1.96 ± 0.57) mg/L vs. (2.87 ± 0.79) mg/L, (7.11 ± 1.46) μg/L vs. (8.24 ± 1.57) μg/L, (110.14 ± 10.63) μg/L vs. (129.52 ± 17.96) μg/L, (716.91 ± 105.78) ng/L vs. (965.25 ± 97.41) ng/L, there were statistical differences ( P<0.05). After 3 months of treatment, the levels of finger protein A20, NF-κB in the observation group were lower than those in the control group: (3.57 ± 1.13) % vs. (4.41 ± 1.32) %, (29.87 ± 6.58) ng/L vs. (35.71 ± 10.02) ng/L, there were statistical differences ( P<0.05). Finger protein A20 and NF-κB in patients with chronic cardiac insufficiency were positively correlated with NT-proBNP ( r = 0.487, 0.738, P<0.01). Conclusions:On the basis of conventional treatment, compared with valsartan, the addition of sakubatril valsartan, can improve the cardiac function of patients with chronic cardiac insufficiency, reduce the body′s inflammatory response, reduce the expression of myocardial injury marker NT-proBNP, inhibit the activation of PBMCs NF-κB, and reduce the level offinger protein A20.

Objective To investigate the effect of temperature on cell proliferation and osteogenic differentiation inhibition of preosteoblast induced by hydrogen peroxide(H2 O2).Methods The MC3T3-E1 cells in the logarithmic phase were randomly divided into 0,450,500,550,600,650 μmol·L-1 H2O2 intervention groups and incubated with 0,450,500,550,600,650 μmol·L-1 H2O2 for 2 h,respectively.Other MC3T3-E1 cells in the logarithmic phase were selected and randomly divided into the control group,model group,low-temperature group,and high-temperature group.Cells in the control group were cul-tured in an incubator with 5％CO2 for 24 h at 37 ℃;cells in the model group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 37 ℃;cells in the low-temperature group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 32 ℃;cells in the high-temperature group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 40 ℃.The cell proliferation in all groups was detected by cell counting kit-8.The expression levels of Runt-related transcription factor 2(RUNX2),osteopontin(OPN)and osteocalcin(OC)mRNA were detected by real-time fluorescence quantitave polymerase chain reaction;and the expression levels of RUNX2,OPN and OC protein were detected by Western blot.Results There was no statistically significant difference in cell proliferation among the 0,450 and 500 μmol·L-1 H2O2 intervention groups(P＞0.05);the cell proliferation rate in the 550,600 and 650 μmol·L-1 H2O2 intervention groups was significantly lower than that in the 0,450 and 500 μmol·L-1 H2O2 intervention groups,showing a significant decrease in cell proliferation with the increase of H2O2 concentrations(P＜0.05).In order to ensure that there were enough cells to perform the following experiments,550 μmol·L-1 H2 O2 was chosen.The cell proliferation rate in the model group and the low-temperature group was significantly lower than that in the control group and high-temperature group(P＜0.05);there was no significant difference in the cell proliferation rate between the control group and high-temperature group(P＞0.05).The relative expression of RUNX2 mRNA in the model group and high-temperature group were significantly higher than that in the control group and low-temperature group(P＜0.05);the relative expression of RUNX2 mRNA in the low-temperature group was significantly lower than that in the control group(P＜0.05);there was no significant difference in the relative expression of RUNX2 mRNA between the model group and high-temperature group(P＞0.05).The relative expression of OPN mRNA in the model group,low-temperature group and high-temperature group was significantly higher than that in the control group(P＜0.05);the relative expression of OPN mRNA in the low-temperature group and high-temperature group was significantly higher than that in the model group(P＜0.05);the relative expression of OPN mRNA in the low-tem-perature group was significantly higher than that in the high-temperature group(P＜0.05).The relative expression of OC mRNA in the model group,low-temperature group and high-temperature group was significantly than that in the control group(P＜0.05);the relative expression of OC mRNA in the low-temperature group and high-temperature group was significantly higher than that in the model group(P＜0.05);there was no significant difference in the relative expression of OC mRNA between the low-temperature group and high-temperature group(P＞0.05).The relative expressions of RUNX2,OPN and OC protein the model group,low-temperature group and high-temperature group were significantly lower than those in the control group(P＜0.05);the relative expressions of RUNX2 and OPN protein in the low-temperature group were significantly lower than those in the model group and high-temperature group(P＜0.05);the relative expression of OC protein was significantly lower than that in the high-temperature group(P＜0.05);and there was no siqnificantly difference in the relatiwe experesson of OC protein between the low-temperature group and model group(P＞0.05);the relative expressions of RUNX2,OPN and OC protein in the high-temperature group were significantly higher than those in the model group(P＜0.05).Conclusion The inhibitory effects of H2O2 on cell proliferation and osteogenic differentiation are observed in MC3T3-E1 cells;low-tempera-ture incubation can enhance the inhibition of H2O2 on cell proliferation and osteogenic differentiation in MC3T3-E1 cells,while high-temperature incubation can relieve its inhibitory effect on cell proliferation and osteogenic differentiation.RUNX2,OPN and OC protein might play an important role in cell proliferation and osteogenic differentiation mediated by temperature.

Objective: To explore the clinical features and complications of foreign bodies in the upper gastrointestinal tract in children and to investigate the effectiveness of endoscopic management. Methods: Data of patients with foreign bodies in upper gastrointestinal tract were collected retrospectively at Endoscopy Center, the Children's Hospital, Zhejiang University School of Medicine, from January 2011 to December 2016. Clinical characteristics, the types of foreign bodies, the location and duration of foreign body impaction were summarized. The risk factors of complications and endoscopic removal failure were analyzed by using Logistic regression analysis. Results: A total of 1 334 patients (825 males and 509 females) were enrolled. The median age was 2.5 years, with a range from 0.25 to 15 years and peak age 1-3 years. Twenty patients had esophageal diseases. The most common foreign body ingested was coin (n=964, 72.3%). Foreign bodies were most commonly located in the esophagus (n=1 002, 75.1%), especially in the upper esophagus (n=857, 85.5%). The duration of foreign body impaction ranged from 3 hours to 5 years. Among 1 334 patients, 252 patients (18.9%) developed complications, including ulcers (n=101, 40.0%) and perforations(n=13, 5.2%). The success rate of endoscopic removal was 96.6% (n=1 288). By Logistic regression analysis, sharp foreign body ingestion (OR=6.893, 95%CI: 4.421-10.746) , esophageal impaction (OR=5.253, 95%CI:3.352-8.233) and foreign body impaction longer than 24 hours (OR=4.336, 95%CI:3.091-6.082) were risk factors of complications. Sharp foreign body ingestion was the risk factor of endoscopic failure (OR=5.372, 95%CI:2.773-10.406) . Conclusions Coin is the most common foreign body in upper gastrointestinal tract. Sharp foreign bodies impacted in the esophagus over 24 hours increase the risk of complications. Endoscopic removal of foreign bodies from the upper gastrointestinal tract in children has a high success rate. Sharp foreign body ingestion increases the risk of failure in endoscopic removing.