Currently,with the rapid development of drug delivery technologies,more and more efforts are taken into the efficient therapies for various diseases by delivering biologically-active macromolecules into the target cells directly.Although a certain number of positive treatment results were obtained from the therapies by using the biomacromolecules to cure some diseases,the microenvironment around the target cell still has a great influence on the final treatment effect.Since many diseases and injuries interfere the normal architecture of the extracellular matrix (ECM),the cell adhesion to ECM and the subsequent cellular activities,the normal microenvironment of the cell plays a critical role in maintaining body balance,tissue regeneration and repair.Given these points,this paper reviews the effects of the cellular microenvironment constructed by ECM on the efficacy of bioactive macromolecules,and provides a theoretical basis for future drug design and synthesis of pharmaceuticals.

Objective To investigate the relationship of blood pressure circadian rhythm with myocardial hypertrophy and the changes of autonomic nerve function in patients with essential hypertension (EH). Methods Eighty-two female patients with essential hypertension (EH) underwent 24-hours ambulatory blood pressure monitorings (ABPM), dynamic electrocardiogram (Holter) and echocardiography examination. Patients were classified into non-dipping group (n=40) and dipping group (n=42) according to the result of ABPM. Left ventricular mass index (LVMI), heart rate variability (HRV) in time domain (including SDNN, SDANN, rMSSD, PNN50) and heart rate turbulence (HRT) parameters (including turbulence onset [TO] and turbulence slope [TS]) were measured. Results Compared with those in dipping group, patients in non-dipping group have higher incidence of LVH (19.0% vs 52.5%, P<0.01), greater mean LVMI (112.39±12.79 g/m2 vs 121.98±13.35 g/m2, P<0.01), decreased PNN50 and rMSSD. TS value was decreased while TO was increased in non-dipping group compared with those in dipping group (both P <0.01); patients with LVH showed decreased TS and increased TO, compared with those without LVH. Conclusion In female patients with EH, non-dipping blood pressure circadian is associated with higher incidence of LVH. The HRV and HRT were more remarkably blunted in non-dipping patients, as well as those with LVH.

Objective To determine whether sleep-disordered breathing (SDB) may lead to nocturnal myocardial ischemia and whether the severity of this ischemia may be relieved by nasal continuous positive airway pressure (CPAP). Methods Overnight polysomnogram examination and simultaneous 3-channel Holter monitoring were performed on 76 patients with moderate to severe SDB and no history of coronary heart disease. All the cases were treated with CPAP for one night. ST depression was defined as a ST segment decrease of more than 1 mm from baseline and lasting 1 min or more. The total duration (minutes) of ST depression was indexed to the total sleep time (minutes per hour of sleep). Results Twenty-eight patients (37%) showed ST segment depression during their sleep. Before CPAP treatment, the respiratory disturbance index (RDI) and arousal index were significantly higher during periods of ST depression than when ST segments were isoelectric, whereas no significant difference was found in blood oxygen saturation (SaO2). After the CPAP treatment of patients with ST depression, the duration of ST depression was significantly reduced from 36.8±18.9 to 11.4±13.2 min/h (P＜0.05). ST depression-related indexes, including RDI, arousal index and the percentage of sleep time spent at SaO2 below 90% (TS90/ TST), were all significantly decreased, with RDI from 63.4±23.8 to 8.1±6.6 /h, arousal index from 51.2±18.9 to 9.6±5.4 /h, and TS90/ TST from 50.6±21.4 to 12.9±14.7% (P＜0.05). Conclusion ST-segment depression is rather common in patients with moderate to severe SDB, and CPAP treatment can significantly reduce the duration of ST depression. ST depression in these patients may reflect the myocardial ischemia that really exists and the non-ischemic changes associated with recurrent SDB.

Objective To evaluate the clinic effect of dental operating microscope ( DOM) and ul-trasonic root canal technique in removing fractured root canal instruments .Methods Eight cases with frac-tured instruments located in different parts of root canals were treated with ultrasonic technique under DOM and the results were analyzed .The fractured instruments were divided into stainless steel file , Ni-Ti file and post according to material type .Results Twenty-seven fractured instruments were removed and the total success rate was71.1%.Among them, the success rate of stainless steel file was 71.4%,of Ni-Ti file was 37.5%and of post was 100%.No root canal perforation occurred .According to the place fractured instru-ments located , the success rate of stainless steel file located at upper 1/3 root canals was 100%,at middle 1/3 was 81.8%and at apex 1/3 was 33.3%;the success rate of Ni-Ti file located at middle 1/3 was 60%and at apex 1/3 was 0.In bent root canals , the success rate of stainless steel file located at bent part crown square was 86.7%and at bent part apex square was 20%;the success rate of Ni-Ti file located at bent part crown square was 60%and at bent part apex square was 0.Conclusion DOM combined with ultrasonic root canal technique in removing fractured instruments is effective , but the success rate is relatively low for Ni-Ti files and the cases fractured instruments located at root canal apex 1/3 or bent part apex square .

OBJECTIVETo explore the correlation between metabolic tumour volume (MTV) and microvessel density (MVD) and blood-borne metastasis in colorectal carcinoma.

METHODSThirty-six patients with CRC conformed by pathology underwent PET-CT examination before operation. SUVmax and MTV were obtained by PET VCRA software. The blood vessels were identified with CD34 immunohistochemical staining, and the MVD was recorded. The correlation between SUVmax and MTV with histological differentiation, T stage, MVD and blood-borne metastasis was analyzed.

RESULTSThe SUVmax, MTV and MVD in patients with blood-borne metastasis were 5.15 ± 5.41, (22.99 ± 18.63) cm³ and 14.17 ± 3.63, and were 10.65 ± 3.79, (16.95 ± 11.82) cm³ and 11.27 ± 3.69, respectively, in patients with non-blood-borne metastasis. The differences of SUVmax, MTV and MVD between blood-borne metastasis and non-blood-borne metastasis patients were statistically significant (all P > 0.05). Pearson correlation analysis found that there was no linear correlation between SUVmax and MVD, and the SUVmax was not statistically significant between high and low MVD groups (t = 0.919, P = 0.364). But there was a linear correlation between MTV and MVD (r = 0.621, P = 0.000), and the MTV was statistically significant between high and low MVD groups (t = 3.567, P = 0.001). The receiver-operating characteristic curves showed that MTV could be used to predict blood-borne metastasis of CRC, and the best cutoff value for MTV was 14.975 cm³, and the sensitivity, specificity, negative predictive value and positive predictive value were 85.7%, 54.5%, 72.3% and 64.2%, respectively. There were no significant relationships between SUVmax, MTV, MVD, blood-borne metastasis and histological differentiation (P > 0.05). With the increased T stage, the MTV, MVD and the probability of blood-borne metastasis were also increased (all P < 0.05).

CONCLUSIONSThere are correlations between MTV and MVD and blood-borne metastasis in CRC. The risk of blood-borne metastasis in patients with MTV > 14.975 cm³ is higher, and needs to take more effective intervention.

Colorectal Neoplasms ; blood supply ; diagnostic imaging ; pathology ; Fluorodeoxyglucose F18 ; Humans ; Microvessels ; pathology ; Multimodal Imaging ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Positron-Emission Tomography ; ROC Curve ; Radiopharmaceuticals ; Sensitivity and Specificity ; Tomography, X-Ray Computed

Objective: In comparison with thrombus aspiration, to study the safety and effcacy of precise intracoronary retrograde thrombolysis during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).
Methods: A total of 123 consecutive patients with acute STEMI received primary PCI in our hospital from 2014-01 to 2015-12 were enrolled.The patients were randomly divided into 2 groups: RT group, the patients received precise intracoronary retrograde thrombolysis (RT),n=60 and TA group, the patients received thrombus aspiration (TA),n=63, among them, 3 patients with failed TA were excluded. Primary end points included occurrence rates of no-lfow after PCI and ST-segment resolution (STR)≥50% at (60-90) min after PCI; primary safety end points included occurrence rates of in-hospital stroke and TIMI-hemorrhage events.
Results:①Compared with TA group, RT group showed decreased no-lfow rate after PCI (1.7% vs 15.0%),P=0.008 and increased rate of STR≥50% after PCI (65.0% vs 45.0%),P=0.028, improved LVEF by echocardiography (50.7±8.6) % vs (46.7±8.3)%,P=0.011. The in-hospital MACE occurrence rate was similar between 2 groups,P>0.05.②No in-hospital stroke or TIMI-hemorrhage events occurred in neither group.
Conclusion: Intracoronary retrograde precise thrombolysis had the similar safety to thrombus aspiration during primary PCI in patients with acute STEMI, it may reduce no-relfow rate and improve left ventricular function after PCI.

Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both "anabolic responses of mechanical loading" and "BMP-mediated osteogenic signaling"? Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.
Algorithms ; Animals ; Base Sequence ; Binding Sites ; genetics ; Biomechanical Phenomena ; Bone Morphogenetic Proteins ; pharmacology ; Consensus Sequence ; DNA ; genetics ; metabolism ; Databases, Genetic ; Gene Expression Profiling ; statistics & numerical data ; Genomics ; statistics & numerical data ; Mice ; Oligonucleotide Array Sequence Analysis ; statistics & numerical data ; Osteoblasts ; drug effects ; metabolism ; Osteogenesis ; drug effects ; genetics ; physiology ; Transcription Factors ; metabolism

Background and objective Glutl is the main carrier which intervenes the glucose uptake of cell, and the expression of Glutl was positively correlated to the uptake of FDG. The aim of this study is to select the CT characteristics and clinicopathological parameters which can refect the levels of glucose metabolism of human non-small lung cancer (NSLC). Methods Thirty-three cases of the NSLC (squamous carcinoma 11 cases and adenocarcinoma 22 cases) have undergone the scanning of FDG PET/CT before operation. The tumor pathological classification, degree of differentiation and lymph node me-tastasis were collected. The CT characteristics which included the diameter, deep lobulation, thin and short spiculation, spinous protuberance, cavity sign, vessel convergence sign and pleural retraction sign were described. Tracer uptake of suspected lesious was assessed by visual assessment and quantitatively by the maximum standardized uptake values (SUVmax).The expression of Ghitl which were examined by means of SP immunohistochemical technique was also analyzed. Results The positive rate of Glut1 was 66.67% (squamous carcinoma was 90.91% and adenocarcinoma was 54.55%). The positive rate of Glut1 and SUVmax of squamous carcinoma were significant higher than adenocarcinoma (Pbilateral=0.037, Punilateral=0.045). Through visual assess-ment and SUVmax, the uptake and the positive rate of Glutl which size ≥2 cm were higher than the size <2 cm (Pbilateral=0.002,Pbilateral=0.001, Punilateral=0.049). The uptake intense of FDG was related to the thin and short spiculation through visual assessment(Pbilateral=0.006). Conclusion The study suggested that the levels of glucose metabolism of squamous carcinoma higher than ad-enocarcinoma, the diameter upper than 2 cm and the thin and short speculation were higher.

Aim To analyze the risk factor of the cardiac rupture(CR)in patients with acute ST-segment eleva-tion myocardial infarction(STEMI).Based on this,the nomogram model of acute STEMI patients with CR was estab-lished.Methods Through Ningxia Medical University General Hospital's big data research platform and hospital in-formation system retrieval,5 412 patients with acute STEMI from January 2015 to December 2019 were continuously includ-ed in the study,of which 91 patients with CR were included as CR group;5 321 patients non-combined with CR were in-cluded as non-CR group.LASSO regression,univariate and multivariate Logistic regression were used to analyze the risk factors of CR in patients with acute STEMI,and the CR nomogram predictive model was established.The nomogram mod-el was validated and evaluated by using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test and clinical decision curve analysis(DCA).Results LASSO regression results showed that age,female,hypertension history,first medical contact time,shock index,Killip grade,white blood cell count,d-dimer,lactic acid,anterior myocardial in-farction,β-blocker administration within 24 hours,angiotensin converting enzyme inhibitor/angiotensin receptor antagonist(ACEI/ARB)administration within 24 hours,emergency percutaneous coronary intervention(PCI)were 13 risk factors of CR(P＜0.05).The screened 13 risk factors were analyzed by univariate and multivariate Logistic regression,the results suggested that age,Killip grade,first medical contact time,white blood cell count,not undergoing emergency PCI and not taking ACEI/ARB drugs within 24 hours were the risk factors of CR in patients with acute STEMI.The acute STEMI with CR nomogram model was established according to the above 6 risk variables.The area under the ROC curve before and after the internal verification of the nomogram model was 0.946(95％CI:0.927～0.961),0.947(95％CI:0.927～0.959),and the sensitivity was 0.957 and 0.904,respectively,the specificity was 0.858 and 0.876,respectively,which indicated that the model had good discrimination degree.The Hosmer-Lemeshow test showed that the deviation between the predicted value and the observed value was not statistically significant(x2=12.70,P=0.122),indicating that the no-mogram model had a good calibration.The DCA curve indicated that the predictive probability threshold of the model was from 0.00 to 0.40,and the clinical net benefit was the highest,indicating that the model had good clinical efficacy.Conclusion The nomogram model established in this study has better distinction,calibration and clinical effectiveness.It can effectively predict the probability of acute STEMI with CR,and provide some help for clinical diagnosis and treat-ment,so as to reduce the incidence of CR.

Objective To investigate the clinical significance of bone marrow immunopathogenesis in the diagnosis and staging of lymphoma. Methods Clinical data of 266 patients with newly diagnosed lymphoma admitted to Department of Hematology in the First Hospital of Jilin University from August 2015 to December 2017 were retrospectively analyzed. The results of lymphoma diagnosis and staging in different bone marrow detection methods were compared, SPSS 22.0 software was used to make statistical analysis and χ2 test was used to compare the positive rates of lymphoma bone marrow infiltration in different methods. Results In the 266 patients, 64 cases (24.1 %) were diagnosed with lymphoma by using bone marrow detection on the condition that no lymph node pathology was available and all the immunophenotypes of 64 cases were identified by bone marrow immunopathology. Bone marrow infiltration was identified in 121 patients (45.5 %), among which the rate of bone marrow infiltration was 0 (0/12) in Hodgkin lymphoma (HL) and 47.6 % (121/254) in non-Hodgkin lymphoma (NHL). The rate of bone marrow infiltration was 50.0 % (105/210) and 36.4 % (16/44) in B type and T type NHL respectively. The positive rate of bone marrow infiltration detected by bone marrow smear, bone marrow biopsy, bone marrow flow cytometry and bone marrow immunopathology were 78.5 % (95/121), 87.6 % (106/121), 89.3 % (108/121), 96.7 % (117/121) respectively. Bone marrow immunopathology was more advantageous than any other methods, and there was a statistical difference (χ2＝18.38, 9.09, 3.76; all P < 0.05). Among 121 patients who were identified with bone marrow infiltration by bone marrow detection, the staging of 42 patients (34.7 %) were amended, including the staging of 39 amended patients (32.2 %) through bone marrow immunopathologic detection. Conclusion Bone marrow immunopathology can be used for the diagnosis and classification of lymphoma, which has an obvious advantage in detecting bone marrow infiltration of lymphoma compared with bone marrow smear, bone marrow biopsy, bone marrow flow cytometry, and it can be used to amend the clinical staging.