Tubiechong patching promotes tibia fracture healing in rats by regulating angiogenesis through the VEGF/ERK1/2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The external use of traditional Chinese medicine (TCM) to treat fractures has a long history of clinical application and theoretical basis, and is also one of the characteristic treatment methods of TCM with significant efficacy and many advantages. Among the commonly used external Chinese medicines, Tubiechong is noteworthy. AIM OF THE STUDY: To elucidate whether local patching of Tubiechong can promote fracture healing and explore its mechanism of action. MATERIALS AND METHODS: A rat tibia fracture model was constructed by the modified Einhorn modeling method. X-ray films were taken to evaluate the progress of fracture healing. Serum bone alkaline phosphatase (BALP), osteocalcin (BGP) and the C-terminal content of collagen type I (CTX-I) were analyzed by ELISA. CD31 immunohistochemistry was used to evaluate angiogenesis in the tibia segment. The effects of Tubiechong decoction (TD) on HUVEC proliferation, migration and invasion were detected by MTT assay, wound healing assay and Transwell migration assay, respectively. RNA-seq was performed to identify differentially expressed genes (DEGs). Enrichment of functions and signaling pathway analysis were performed based on the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real time polymerase chain reaction (qRT-PCR) was used to study gene expression levels. Western blotting (WB) was used to detect the expression of relevant regulatory proteins. RESULTS: The healing time of rat tibia fractures in the three TD dose groups was shortened. The serum levels of BALP, BGP and CTX- I in the TD-treated group were higher than those in the NC group. The X-ray results showed that on the 7th day after surgery, the fracture healing degree of the high-dose TD group was significantly better than that of the NC group, and the fracture healing degrees of each TD treatment group were significantly higher than those of the NC group on the 14th, 17th, and 21st days after the operation. The CD31 immunohistochemistry results showed that the number of blood vessels and the vascular area in the TD treatment group were higher than those in the NC group. In vitro, TD promoted the proliferation, wound healing and migration of HUVECs. GO analysis of transcriptome sequencing results showed that TD significantly altered the expression of genes related to cell growth, metabolism, and motility. According to KEGG annotations, VEGFA was upregulated. Eight DEGs were enriched in the VEGFA-VEGFR2 signaling pathway, of which six were upregulated. KEGG signaling pathway analysis showed that the most abundant DEGs were in mitogen-activated protein kinase (MAPK) signaling pathway. qRT-PCR showed that VEGFA gene expression in HUVECs was 7.8 times that of the control group after 1 mg/mL TD treatment for 24 h, and WB experiments showed that its protein expression was 3 times that of the control group. WB results showed that the phosphorylated ERK gene was highly expressed, while the expression levels of phosphorylated P38 and phosphorylated JNK protein remained unchanged. CONCLUSION: Tubechong patching therapy promotes tibia fracture healing in rats by regulating angiogenesis through the VEGF/ERK1/2 signaling pathway.

[Isolation and Biological Characterization of Lung Cancer Stem Cells].

Objective To explore the methods of screening and biological characteristics of lung cancer stem cells. Methods We selected the ABCG2 +and ABCG2 -cells from SPC-A-1/adriamycin(ADM)cell line induced by ADM and analyzed the tumorigenicity of ABCG2 +and ABCG2 -cells in vivo by flow cytometry and transplantation in nude mice. Results The average fluorescence intensity of SPC-A-1 cells was(1.001±0.014)×10 2,which was significantly lower than that of SPC-A-1/ADM cells [(10.257±0.023) ×10 2 ](t=17.320,P=0.001);the difference was also statistically significant between the ABCG2/BCRP-FITC treatment group and the SPC-A-1 control group(t=5.269,P=0.021) and the SPC-A-1 control group(t=6.869, P=0.012) and between the SPC-A-1/ADM cell control group and the SPC-A-1/ADM cell homotype control group(t=8.112,P=0.015).The positive rate of SPC-A-1/ADM cells treated with ABCG2/BCRP-FITC was 9.8%,39.84 times higher than that of SPC-A-1 cells;it showed significant difference between the ABCG2/BCRP-FITC group and the SPC-A-1/ADM group(t=9.120,P=0.005) and the SPC-A-1/ADM group(t=8.257,P= 0.006).The positive rate of group B cells was 684 times that of group A cells,and the difference was statistically significant(t=11.235,P=0.001),and the fluorescence intensity of group B cells was strong.The average tumorigenic volume of the mice inoculated with SPC-A-1 cells,group A cells,and group B cells was(6.96±1.82),(6.70±2.55),and(9.17±2.41) mm 3,respectively.Among them,group B was the highest,but there was no significant difference among these three groups(F=2.362,P=0.086).The tumorigenic rate of group B cells was 75.00%,which was significantly higher than that of SPC-A-1 cells and group A cells(F=19.780,P=0.002). Conclusion ABCG2 cells from human lung adenocarcinoma SPC-A-1/ADM cell line can be isolated by ABCG2 antibody combined with immunomagnetic beads sorting method,and the tumor formation rate in nude mice can be observed to explore the identification and biological characterization of lung cancer stem cells.

Conversion therapy and suitable timing for subsequent salvage surgery for initially unresectable hepatocellular carcinoma: What is new?

AIM: To review the conversion therapy for initially unresectable hepatocellular carcinoma (HCC) patients and the suitable timing for subsequent salvage surgery. METHODS: A PubMed search was undertaken from 1987 to 2017 to identify articles using the keywords including "unresectable" "hepatocellular carcinoma", "hepatectomy", "conversion therapy", "resection", "salvage surgery" and "downstaging". Additional studies were investigated through a manual search of the references from the articles. The exclusion criteria were duplicates, case reports, case series, videos, contents unrelated to the topic, comments, and editorial essays. The main and widely used conversion therapies and the suitable timing for subsequent salvage surgery were discussed in detail. Two members of our group independently performed the literature search and data extraction. RESULTS: Liver volume measurements [future liver remnant (FLR)/total liver volume or residual liver volume/bodyweight ratio] and function tests (scoring systems and liver stiffness) were often performed in order to justify whether patients were suitable candidates for surgery. Successful conversion therapy was usually defined as downstaging the tumor, increasing FLR and providing subsequent salvage surgery, without increasing complications, morbidity or mortality. The requirements for performing salvage surgery after transcatheter arterial chemoembolization were the achievement of a partial remission in radiology, the disappearance of the portal vein thrombosis, and the lack of extrahepatic metastasis. Patients with a standardized FLR (sFLR) > 20% were good candidates for surgery after portal vein embolization, while other predictive parameters like growth rate, kinetic growth rate were treated as an effective supplementary. There was probably not enough evidence to provide a standard operation time after associating liver partition and portal vein ligation for staged hepatectomy or yttrium-90 microsphere radioembolization. The indications of any combinations of conversion therapies and the subsequent salvage surgery time still need to be carefully and comprehensively evaluated. CONCLUSION: Conversion therapy is recommended for the treatment of initially unresectable HCC, and the suitable subsequent salvage surgery time should be reappraised and is closely related to its previous therapeutic effect.

[Hygroscopic Properties and Closure of Aerosol Chemical Composition in Mt. Huang in Summer].

The hygroscopic properties of aerosol have significant impact on aerosol optical properties, cloud condensation nuclei activity and human health. Aerosol particles growth factor and size-resolved ions chemical compositions were monitored in Mt. Huang. The hygroscopic properties of aerosol particles in Mt. Huang were studied. The results demonstrated that between 70 nm and 230 nm, the mass fractions of (NH4)2SO4, organic matter and other insoluble materials were the highest. The fraction of NH4NO3 standed in the medium. The fraction of NH4HSO4 was the lowest. The fraction of inorganic salts increased with increasing particle diameter. Aerosol particles during daytime had stronger hygroscopicity than that at night and the hygroscopicity of aerosol became stronger when its diameter increased. The calculation hygroscopic parameter κ of aerosol particles showed similar diurnal variation characteristics to the observation κ. Good closure could be achieved when ZSR mixing rule was used based on aerosol chemical composition to calculate aerosol hygroscopic parameter κ and the coefficient of determination was 0.60 for all the diameters.

[Sources Analysis of Heavy Metal Aerosol Particles in North Suburb of Nanjing].

Heavy metal aerosol particles were first measured with Single Particle Aerosol Mass Spectrometry (SPAMS) in north suburb of Nanjing from January to December, 2013. Using the ART-2a neural network algorithm, we studied the chemical characteristics of aerosol particles and found that the main sources of heavy metal aerosols in Nanjing were industrial emissions, biomass burning, traffic emissions, fuel combustion and dust, accounting for 35.7%, 34.45%, 13.6%, 11.03% and 4.07% respectively. Pb, Cd and Cr-containing aerosols mainly came from industrial emissions. Cu, Co and Hg-containing aerosols mainly came from biomass burning. V, Zn and Ba-containing aerosols mainly came from traffic emissions. As and Ni-containing aerosols mainly came from fuel combustion.

[Hygroscopic Properties of Aerosol Particles in North Suburb of Nanjing in Spring].

The hygroscopic properties of submicron aerosol particles have significant effects on spectral distribution, CCN activation, climate forcing, human health and so on. A Hygroscopic Tandem Differential Mobility Analyzer (HTDMA) was utilized to analyze the hygroscopic properties of aerosol particles in the northern suburb of Nanjing during 16 April to 21 May, 2014. At relative humidity (RH) of 90%, for particles with dry diameters 30-230 nm, the probability distribution of GF (GF-PDF) shows a distinct bimodal pattern, with a dominant more-hygroscopic group and a smaller less-hygroscopic group. A contrast analysis between day and night suggests that, aerosol particles during day time have a stronger hygroscopicity and a higher number fraction of more-hygroscopic group than that at night overall. Aerosol particles during night have a higher degree of externally mixed state. Backward trajectory analysis using HYSPLIT mode reveals that, the sampling site is mainly affected by three air masses. For aitken nuclei, northwest continental air masses experience a longer aging process and have a stronger hygroscopicity. For condensation nuclei, east air masses have a stronger hygroscopicity and have a higher number fraction of more-hygroscopic group. Aerosol particles in local air masses have a high number fraction of more-hygroscopic group in the whole diameter range.

The effect of early and late tracheotomy on outcomes in patients: a systematic review and cumulative meta-analysis.

OBJECTIVE: To compare the effect of early tracheotomy (ET) and late tracheotomy (LT) on ventilator-associated pneumonia (VAP) incidence and short-term mortality in critically ill patients who received mechanical ventilation. DATA SOURCES: We searched databases of PubMed, Embase, and others for randomized controlled trials (RCTs) that compared ET (≤ 8 days after admission to the intensive care unit, initiation of translaryngeal intubation, or initiation of mechanical ventilation) with LT (≥ 6 days) in critically ill patients. REVIEW METHODS: The overall odds ratio (OR) was estimated by traditional meta-analysis. In addition, cumulative meta-analysis was conducted by adding 1 study at a time in the order of year of publication. RESULTS: A total of 11 RCTs involving 1436 patients (708 in the ET group and 728 in the LT group) were included in this analysis. Early tracheotomy could significantly reduce the short-term mortality (OR = 0.74; 95% confidence interval [CI] [0.58, 0.95]) but did not reduce the VAP incidence (OR = 0.70; 95% CI [0.47, 1.04]). The cumulative meta-analysis showed that evidence of the benefit of ET on VAP incidence was unstable over time. In contrast, the difference in short-term mortality was stable from the first appearance during the cumulative meta-analysis. CONCLUSION: Early tracheotomy could improve short-term mortality but did not alter VAP incidence. Many factors may be responsible for the unstable results during cumulative meta-analysis, and further study is still needed to explore the optimal timing of tracheotomy.

[Size distributions of aerosol during the Spring Festival in Nanjing].

In order to investigate the firework burning impacts on spectrum distribution of atmospheric aerosol during the Spring Festival in Nanjing, number concentration and mass concentration of aerosol as well as mass concentration of gas pollutants were measured during January 19-31, 2012. The results indicated that the concentration of aerosol between 10-20 nm decreased, aerosol concentration in the range of 50-100 nm, 100-200 nm and 200-500 nm increased during the firework burning period comparing to those during the non-burning period. However, there was no obvious variation for aerosol between 20-50 nm and 0.5-10 microm. The spectrum distribution of number concentration was bimodal during the non-burning period and unimodal during the burning period, with the peak value shifting to large diameter section. The mass concentration presented a bimodal distribution, the value of PM2.5/PM10 and PM10/PM10 increased by 10% during the burning period. The firework burning events had big influence on the density of aerosol between 1.0-2.1 microm.

Risks of proteinuria associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: a systematic review and meta-analysis.

BACKGROUND: Vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) have emerged as an effective targeted therapy in the treatment of cancer patients, the overall incidence and risk of proteinuria associated these drugs is unclear. We performed a systematic review and meta-analysis of published clinical trials to quantify the incidence and risk of proteinuria associated with VEGFR-TKIs. METHODOLOGY: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating VEGFR-TKIs in cancer patients with adequate data on proteinuria. Statistical analyses were conducted to calculate the summary incidence, Odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. PRINCIPAL FINDINGS: A total of 6,882 patients with a variety of solid tumors from 33 clinical trials were included in our analysis. The incidence of all-grade and high-grade (grade 3 or higher) proteinuria was 18.7% (95% CI, 13.3%-25.6%) and 2.4% (95% CI, 1.6%-3.7%), respectively. Patients treated with VEGFR-TKIs had a significantly increased risk of all-grade (OR 2.92, 95%CI: 1.09-7.82, p = 0.033) and high-grade proteinuria (OR 1.97, 95%CI: 1.01-3.84, p = 0.046) when compared to patients treated with control medication. No evidence of publication bias was observed. CONCLUSIONS: The use of VEGFR-TKIs is associated with a significant increased risk of developing proteinuria. Physicians should be aware of this adverse effect and should monitor cancer patients receiving VEGFR-TKIs.

[Analysis on the correlation between SF-36 and QOL-35 in patients and coronary artery disease].

OBJECTIVE: To analyze the correlation between SF-36 and QOL-35 and the consistency of the two kinds of life-quality questionnaires when evaluating the quality of life in patients with coronary heart disease. METHODS: 781 in-hospital-patients, who underwent coronary angiography from June 2008 to April 2009, were included in this study. Quality of life was measured by the Chinese versions of SF-36 and QOL-35. Demographic and clinical information were collected. Correlation Analysis was done between SF-36 and QOL-35 in the patients with coronary artery disease. RESULTS: The total score of SF-36 was 62.63 ± 12.47 and the QOL-35 total score was 62.70 ± 9.69. Data from the simple correlation analysis showed that SF-36 and QOL-35 total scores (r = 0.725, P < 0.01), SF-36 physical functioning and QOL-35 independent living capacity (r = 0.933, P < 0.01), SF-36 mental health and QOL-35 mental health(r = 0.132, P < 0.01), SF-36 social function and QOL-35 social function score (r = 0.215, P < 0.01) were all relevant. Canonical correlation analysis showed that there was significant correlation between SF-36 and QOL-35 (r = 0.946, P < 0.01). CONCLUSION: SF-36 and QOL-35 were consistent in the evaluation on the quality of life, at the overall level.

[Covariance analysis on the change of quality of life affected by percutaneous coronary intervention for patients with coronary heart disease].

OBJECTIVE: To compare changes of quality of life at 3 months from baseline among patients who underwent and did not undergo percutaneous coronary intervention (PCI). METHODS: Sixty one patients with coronary artery disease, who were hospitalized in Cardiology Department in March 2008, were followed-up for 3 months after being discharged. SF-36 and QOL-35 were administered before PCI and at 3 months. Patients were divided into 2 groups according to whether they underwent PCI. Changes of quality of life scores between PCI and non-PCI groups were compared using analysis of covariance. RESULTS: There were 24 cases in non-PCI group and 37 in PCI group. Baseline characteristics were well balanced between PCI and non-PCI groups except gender (67.6% vs. 28.6% for male, P = 0.005), history of angina (56.8% vs. 23.8%, P = 0.015), smoking history (51.4% vs.23.8%, P = 0.037) and Judkins classification of coronary artery (P = 0.001). Multivariate analysis of covariance showed that the change of life quality between non-PCI group and PCI group in 3-months after discharge had statistical differences in total scores (P = 0.044) and mental health scores (P = 0.003) of SF-36, total scores (P = 0.039) and social function scores (P = 0.007) of QOL-35. CONCLUSION: PCI can improve life quality in patients with coronary artery disease.

Potential biomarkers for esophageal carcinoma detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: Currently, no satisfactory biomarkers are available to screen for esophageal squamous cell carcinoma (ESCC). The goal of this study was to find biomarkers and establish a serum protein fingerprint model for early diagnosis of ESCC using the ClinProt protocol of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). METHODS: Serum samples were collected from 62 patients with ESCC, nine patients with esophageal adenocarcinoma (EA) and 38 healthy individuals. Proteomic spectra of mass to charge ratio (m/z) were generated following the application of plasma to weak cationic-exchanger magnetic beads (WCX-MB). The spectral data were analyzed using a support vector machine, and potential biomarkers were chosen for system training and used to construct diagnostic models. RESULTS: Three differential patterns were established using MALDI-TOF MS. Pattern 1, consisting of 11 protein peaks, separated ESCC patients from the healthy individuals with a sensitivity of 90.0% and a specificity of 88.4%. Pattern 2, consisting of eight protein peaks, separated ESCC in stage I and stage II from stage III and stage IV with a sensitivity of 92.9% and a specificity of 82.3%. Pattern 3, consisting of seven protein peaks, separated ESCC from EA with a sensitivity of 91.3% and a specificity of 80.0%. CONCLUSIONS: These results suggested that MALDI-TOF MS combined with MB separation yields significantly higher sensitivity and specificity for the detection of serum protein in patients with ESCC.

[Assessment of life quality in patients with chronic heart failure].

OBJECTIVE: Using Kansas city cardiomyopathy questionnaire (KCCQ) to evaluate the quality of life (QOL) of the patients with chronic heart failure. METHODS: A total of 271 hospitalized patients with heart failure symptoms in cardiology department, Peking Union Medical College Hospital, who undergone coronary angiography from December 2007 to December 2008, were included in this study. QOL of the subjects was measured, and their demographic and clinical data were collected. Patients were divided into 2 groups according to heart function and they were compared by QOL.Multiple linear regression analysis was conducted to identify the variables associated with the quality of life. RESULTS: KCCQ physical limitation scores of the patients of left ventricular elective fraction (LVEF) < 50% (n = 50) and LVEF > or = 50% (n = 221) were (66 +/- 22) points and (73 +/- 22) points (P < 0.05). In the patients of NYHA I/II (n = 227) vs NYHA III/IV (n = 44), KCCQ scores of physical limitation, symptoms and QOL were (74 +/- 20) vs (60 +/- 27) points, (62 +/- 22) vs (49 +/- 25) points and (61 +/- 16) vs (53 +/- 18) points (all P < 0.05). In the patients of heart failure grade A/B (n = 197) vs grade C/D (n = 74), KCCQ scores of physical limitation, symptoms and QOL were (75 +/- 19) vs (61 +/- 26) points, (63 +/- 22) vs (52 +/- 24) points, (61 +/- 16) vs (56 +/- 18) points (all P < 0.05). Multiple linear regression analysis of QOL KCCQ showed that, age, NYHA cardiac function classification, gender and Judkins score were the risk factors of patients' physical limitation (P < 0.01); gender and stages of heart failure were the risk factors of patients'symptoms (P < 0.01); gender was the risk factors of patients'social function (P < 0.01). CONCLUSION: The patients with poor cardiac function have a poor QOL. KCCQ is more sensitive for the evaluation of heart function. Age, NYHA, gender, Judkins score and stages of heart failure can change QOL for the patients with chronic heart failure.

[Assessment of quality of life in patients with coronary artery disease with Seattle angina questionnaire].

OBJECTIVE: To evaluate quality of life (QOL) of patients with different severity of coronary artery disease using Seattle angina questionnaire (SAQ). METHODS: A total of 513 hospitalized patients undergoing coronary angiography from December 2007 to December 2008 were included. QOL of these patients was measured with SAQ and their demographic and clinical data were collected. Patients were divided into 3 groups according to the severity of coronary artery disease by coronary angiography. And comparisons of traditional risk factors and QOL were made among these groups. Multiple linear regression analysis was conducted to identify the variables associated with QOL. RESULTS: The scores of physical limitation were significantly different among 3 groups according to the severity of coronary artery disease by coronary angiography (80 +/- 16, 79 +/- 19 and 71 +/- 22, P < 0.01). Multiple linear regression analysis showed that physical limitation of the patients was affected by age (P < 0.01), gender (P < 0.01) and severity of coronary artery disease (P < 0.01). Angina stability was affected by the history of myocardial infarction (P = 0.03). Angina frequency was affected by the history of myocardial infarction (P = 0.01) and gender (P = 0.04). Treatment satisfaction was affected by the severity of coronary artery disease (P = 0.03) and disease perception by the history of DM (P = 0.03). CONCLUSION: Age, gender, history of myocardial infarction, history of DM and severity of coronary artery disease are independent predictors of QOL in patients with coronary artery disease.