[Consistency of peripheral whole blood and venous serum procalcitonin in children: a multicenter parallel controlled study].

Objective: To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection. Methods: This multicenter cross-sectional parallel control study was conducted in 11 children's hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman's rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection. Results: A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum (r=0.97, P<0.01). The linear regression equation was PCTvenous serum=0.135+0.929×PCTperipheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods (r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 µg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 µg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 µg/L, respectively. Conclusions: There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

MicroRNA-30a-3p inhibits malignant progression of hepatocellular carcinoma through regulating IGF1.

OBJECTIVE: The purpose of this study was to investigate the expression level of microRNA-30a-3p in hepatocellular carcinoma (HCC), and to further study its relationship with HCC clinical parameters and prognosis and the underlying mechanisms. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine microRNA-30a-3p level in 44 tumor tissue specimens and paracancerous normal ones collected from HCC patients, and the interplay between microRNA-30a-3p expression and clinical indicators, as well as prognosis of HCC patients was analyzed. Meanwhile, qPCR was also used to further verify microRNA-30a-3p expression in HCC cell lines. In addition, microRNA-30a-3p overexpression and knockdown models were constructed in HCC cell lines, and the impacts of microRNA-30a-3p on HCC cell functions was evaluated by cell counting kit-8 (CCK-8), transwell and cell wound healing assays. Finally, the Luciferase reporting assay was conducted to uncover the underlying mechanism. RESULTS: In this study, qRT-PCR results showed that the expression level of microRNA-30a-3p in tumor tissues of HCC patients was markedly lower than that in adjacent ones. Compared with patients with high expression of microRNA-30a-3p, the patients with low expression of microRNA-30a-3p had a higher incidence of lymphatic or distant metastasis and a lower overall survival rate. In the Bel-7402 cell line, the proliferation, invasion, and metastasis ability of HCC cells were decreased markedly after microRNA-30a-3p overexpression, while in Hep3B cell line, knockdown of microRNA-30a-3p enhanced the cell proliferation and invasion capacity. In addition, Luciferase reporting assay demonstrated that microRNA-30a-3p could specifically bind to IGF1. Furthermore, Western Blot results also verified a reduced expression of IGF1 after overexpression of microRNA-30a-3p, and an elevated one after knockdown of microRNA-30a-3p. Finally, cell recovery experiment verified that microRNA-30a-3p and IGF1 may regulate each other and thereby together inhibit the malignant progression of HCC. CONCLUSIONS: MicroRNA-30a-3p expression is significantly decreased in HCC tumor tissue samples, which is associated with lymph node or distant metastasis rate, as well as the poor prognosis of HCC. In addition, this research suggests that microRNA-30a-3p may inhibit the malignant progression of HCC by regulating IGF1.

Transcription factor ZNF703 activates linc-UBC1 to stimulate the progression of glioma.

OBJECTIVE: To investigate the role of the transcription factor Zinc finger 703 (ZNF703) in influencing the progression of glioma by regulating linc-UBC1 level. MATERIALS AND METHODS: Linc-UBC1 level in glioma with different staging and tumor sizes was determined. The potential influences of linc-UBC1 on viability, cell cycle progression, and invasiveness of glioma cells were evaluated. Through RNA binding protein immunoprecipitation (RIP) assay and Dual-Luciferase reporter gene assay, the interaction between ZNF703 and linc-UBC1 was assessed. The rescue experiments were conducted to identify the role of ZNF703 in regulating cellular performances of glioma by interacting with linc-UBC1. RESULTS: Linc-UBC1 was highly expressed in glioma. Its level was higher in glioma with larger tumor size or advanced staging. The knockdown of linc-UBC1 reduced viability, arrested cell cycle in the G0/G1 phase, and attenuated invasiveness of U87 and LN229 cells. The presence of the binding sites was observed in the promoter regions of ZNF703 and linc-UBC1. The overexpression of ZNF703 could alleviate the inhibited proliferative and invasive potentials in U87 and LN229 cells with the linc-UBC1 knockdown. CONCLUSIONS: The transcription factor ZNF703 promotes the proliferative and invasive potentials in glioma cells by regulating the transcriptional activity of linc-UBC1.

[Association between the frequency of bowel movements and the risk of colorectal cancer in Chinese adults].

Objective: To examine the association between the frequencies of bowel movement (BMF) and the risk of colorectal cancer (CRC). Methods: In this study, 510 134 participants from the China Kadoorie Biobank (CKB) were included, after excluding those who reported as having been diagnosed with cancer at the baseline survey. The baseline survey was conducted from June 2004 to July 2008. The present study included data from baseline and follow-up until December 31, 2016. We used the Cox proportional hazards regression models to estimate the HR and the 95%CI of incident CRC with BMF. Results: During an average follow-up period of 9.9 years, 3 056 participants were documented as having developed colorectal cancer. In the site-specific analysis, 1 548 colon cancer and 1 475 rectal cancer were included. Compared with participants who had bowel movements on the daily base, the multivariable-adjusted HR (95%CI) for those who had more than once of BMF were 1.24 (1.12-1.39) for CRC, 1.12 (0.95-1.31) for colon cancer, and 1.37 (1.18-1.59) for rectal cancer. We further examined the association between BMF and CRC, according to the stages of follow-up, the corresponding HR (95%CI) for CRC, colon and rectal cancer were 1.59 (1.36-1.86), 1.43 (1.14- 1.80), and 1.76 (1.41-2.19) for the first five years, while such associations became statistically insignificant in the subsequent follow-up (P for all interactions were <0.05), as time went on. As for CRC, colon or rectal cancers among participants who had lower bowel movements, the risks were not significantly different from those who had bowel movements everyday. Conclusions: Participants who had BMF more than once a day, appeared an increased risk of CRC in the subsequent five years. Since abnormal increase of bowel movements is easily recognizable, programs should be set up on health self- management and early screening for CRC.

[The incidence and risk factors of catheter-related-thrombosis during induction chemotherapy in acute lymphocytic leukemia children].

Objective: To investigate the current status of catheter-related-thrombosis (CRT) and the risk factors of Chinese acute lymphocytic leukemia (ALL) children with peripherally inserted central catheter (PICC) . Methods: The clinical data of the 116 inpatients preliminarily diagnosed ALL in the Leukemia Ward of Beijing Children's Hospital with PICC from 1(st) March 2014 to 31(st) December 2014 were collected prospectively. Results: ①Refer to the B-ultrasound on the 15(th) day after catheterization, the incidence of CRT was 28.4% (33/116 cases) , all cases were symptom-free. ②There were no statistical differences in terms of gender, age distribution, degree, immunotype between CRT and CRT-free groups. This study revealed no statistical differences of blood routine test items, coagulation function items, co-infection and catheterization vein between the two groups. While there was significant statistical difference of catheterization side, the frequency of right catheterization was higher in CRT group[75.8% (25/33) vs 55.4% (46/83) , P=0.043]. ③On the 15(th) day after catheterization, significant statistical difference of D-Dimer between the two groups was revealed[0.18 (0.05-2.45) mg/L vs 0.11 (0.01-5.34) mg/L, P=0.001], while no statistical differences of blood routine test items and other coagulation function items. Multivariate Logistic regression analysis verified catheterization on right was a risk factor of CRT. ④During the observation, there were 3 cases of catheter-related complications other than CRT, all of which were CRI, 2 of them had CRT meanwhile. ⑤The B-ultrasound on the 33(rd) day after catheterization showed that 73.1% of the cases had reduced thrombosis, 3.8% had growth thrombosis, 23.1% had no obvious change respectively. Conclusion: CRT was a common catheter related complication among ALL children during induction chemotherapy, and CRT cases with symptoms were rare. Catheterization on right was a risk factor for CRT, and regular test of D-Dimer and B ultrasound contributed to detect CRT. Most of the CRT cases had reduced thrombosis without specific management.

TNF alpha inhibits myogenic differentiation of C2C12 cells through NF-κB activation and impairment of IGF-1 signaling pathway.

Cachexia or muscle wasting is a common condition that occurs in many chronic diseases. The wasting conditions are characterized by increased levels of TNF-α which was also known as cachectin in the past. But how TNF-α exerts its cachetic effects remains controversial. To clarify this issue, we investigated the impact of TNF-α on C2C12 cell myogenic differentiation. Our results demonstrate that myotube formation was completely inhibited by TNF-α when added to differentiating C2C12 myoblasts. The inhibitory effect of TNF-α on differentiation was accompanied by activation of NF-κB and down regulation of myogenin and Akt. Importantly, TNF-α's effect on differentiation was abolished when IGF-1 was added to the culture. IGF-1 treatment also inhibited NF-κB reporter activity and restored Akt levels. Our data suggest that TNF-α inhibits myogenic differentiation through NF-κB activation and impairment of IGF-1 signaling pathway. The reversal of TNF-α induced inhibition of myogenesis by IGF-1 may have significant therapeutic potential.

Preparation and in vitro evaluation of B-lipiodol as a boron delivery agent for neutron capture therapy of hepatoma.

BACKGROUND: We prepared boron containing lipiodol (B-lipiodol), elucidated the retention of B-lipiodol in hepatoma cells and evaluated the in vitro cellular toxicity of B-lipiodol for neutron capture therapy. MATERIALS AND METHODS: Human hepatoma HepG2 cells were used to examine the uptake and retention of B-lipiodol. Light microscopes were used to examine the interaction and retention of B-lipiodol globules in individual hepatoma cells. Boron and lipiodol concentrations were determined by inductively coupled plasma-atomic emission spectroscopy and neutron activation analysis, respectively. RESULTS: The boron concentration in B-lipiodol drug could reach 2500 ppm. B-lipiodol could be stably retained in serum and culture medium. HepG2 cells appeared proficiently at internalization and persistent retention of B-lipiodol. The boron concentration reached 3.5 micrograms/10(6) cells without approaching saturation at 48 h treatment. CONCLUSION: Hepatoma cells could actively uptake B-lipiodol and a sufficient amount of boron was retained inside the HepG2 cells which could be used for neutron capture therapy.

Tissue potassium, selenium, and iron levels associated with gastric cancer progression.

The contents of 10 minor and trace elements in histologically confirmed gastric adenocarcinomas and their corresponding normal gastric mucosal tissues obtained from 39 patients at the time of gastric resection were simultaneously determined by instrumental neutron activation analysis. Specimens were irradiated by reactor neutrons and subsequently subject to direct analysis using a high-resolution HPGe gamma-spectrometer. Univariate analysis revealed that gastric cancer tissues had significantly higher concentrations of Fe, K, Mg, Na, Rb, Se, and Zn than normal gastric mucosal tissues. However, multivariate analysis found that Fe, K, and Se were independent elements that associated with gastric cancer. Upon further evaluation of their clinical significance, we found a high tissue K level was related to lymphatic duct metastasis. High Se tissue levels were linked to intestinal type adenocarcinoma. A positive correlation was found between high Fe levels and vascular involvement. These findings suggest that Fe and K are associated with gastric cancer progression. Se is involved in carcinogenesis of stomach in high-risk areas. The mechanisms that underlie the corresponding pathohistological features deserve further study.

Analysis of elemental absorption and excretion in mice bearing malignant ascites.

Feces, kidney, and small intestine were sampled from the mice bearing malignant ascites at different stages of tumor growth to investigate the kinetics of elemental distribution in the body. The contents of 14 elements in samples were determined by instrumental neutron activation analysis (INAA). The elements Br, Cl, Cu, Na, Se, and Zn increased, whereas Mn and Rb decreased in kidney with the growth of the tumor. The elements Cl, Na, and Fe, however, appeared to have significantly different behavior in the small intestine.

Determination of whole-body nitrogen and radiation assessment using in vivo prompt gamma activation technique.

Body nitrogen content in the phantom is measured by semiconducting and scintillation spectrometers using in vivo prompt gamma-ray activation analysis technique. The effective dose rate equivalents for sensitive organs and tissues inside the phantom are assessed by dosimetric measurement and neutron transport calculation. The bismuth germanate scintillator is found superior to the germanium semiconducting detector to quantitatively measure the photopeak of the 10.829 MeV prompt gamma-ray emitted from the 14N(n, gamma) reaction. Recommended scanning period for current setup using the BGO detector is 1 h on the modified mobile nuclear reactor. The effective dose equivalents from both neutrons and gamma-rays are estimated around 63 microSv per scan in the phantom test, making it a safe and reliable nuclear analytical method for in vivo body nitrogen measurement.

Cytochrome b560 (QPs1) of mitochondrial succinate-ubiquinone reductase. Immunochemistry, cloning, and nucleotide sequencing.

Mitochondrial succinate-ubiquinone reductase is composed of two parts, a water-soluble succinate dehydrogenase and a two-polypeptide membrane-anchoring protein fraction (QPs). The larger polypeptide of QPs is believed to be associated with cytochrome b560 (QPs1). The structure of QPs1 was studied by immunochemistry and molecular cloning and sequencing. Antibodies against QPs1 were raised in rabbits, purified, and characterized by enzyme-linked immunosorbent assay and Western blotting. The purified antibodies inhibited 75% of the reconstitutive activity of QPs and reacted with both submitochondrial particles (SMP) and mitoplasts. The binding of these antibodies to SMP was greatly increased when succinate dehydrogenase was removed from SMP by alkaline treatment, indicating that QPs1 is a transmembranous protein and that some of its specific epitopes are covered by succinate dehydrogenase. Anti-QPs1 antibodies were used to screen one cDNA clone encoding QPs1 from a bovine heart cDNA lambda gt11 expression library. The cDNA insert is 946 base pairs with an open reading frame of 396 base pairs that encodes for 132 amino acid residues. The molecular weight of QPs1, calculated from the deduced amino acid sequence, is 14,320. Although the apparent molecular weight of QPs1, estimated by high resolution SDS-polyacrylamide gel electrophoresis, is approximately 11,000, the existence of a presequence was ruled out by mass spectrometric analysis of protein fragments. QPs1 is a very hydrophobic protein. Three probable membrane-spanning segments were revealed by a hydropathy plot of the sequence. QPs1 has a higher sequence similarity to the sdhC peptide of Escherichia coli than to the sdhC peptide (cytochrome b558) of Bacillus subtilis. Like the bacterial proteins, QPs1 has 2 conserved histidines at positions 34 and 90. The conserved nature and similar location of these 2 histidines, on the matrix-side surface of the membrane, suggest that they are involved in heme ligation of cytochrome b560.

Preparation of [131I]lipiodol as a hepatoma therapeutic agent.

An isotopic exchange method was used to label lipiodol with 131I. The labelling efficiency was > 92.5%, and the radiochemical purity of [131I]lipiodol was above 98% as determined by ITLC. The influencing factors e.g. the heating temperature, reaction time, pH and storage conditions were studied and the optimum conditions were determined. In a pilot study injecting [131I]lipiodol for the treatment of hepatoma, about 70% of hepatoma patients had a response to the treatment with a reduction of alpha-fetoprotein and decrease of hepatoma sizes. The overall median survival was 9 months (range 2-17 months).

Report of a pilot study of intra-arterial injection of I-131 lipiodol for the treatment of hepatoma.

This pilot study in 10 hepatoma patients investigated the feasibility of using selective targeting of radioisotope (I-131) lipiodol in the treatment of hepatoma patients. Lipiodol is a contrast medium that selectively goes to hepatoma and remains there for a long period as compared with that in normal liver and other tissues. Lipiodol was labelled with I-131 and infused into the hepatoma via the hepatic artery. Selective targeting of I-131 to hepatoma was demonstrated with a radiation dose ratio (hepatoma to normal liver) of up to 25 to 1. The biodistribution data of I-131-lipiodol in this study also confirmed the selective targeting of the radioisotope (I-131) to the hepatoma. Tumor radiation dose up to 26,000 rads can be delivered by this method. The treatment results were encouraging. About 70% of hepatoma patients had response to the treatment with reduction of alpha-fetoprotein and decrease of hepatoma sizes. The overall median survival was 9 months (range 2-17 months). This treatment was simple, safe, effective, non-expensive and well tolerated by all patients without major side effects. The optimal dose, schedule, duration of this treatment are still under investigation.