[Genotype-environment interaction on arterial stiffness: A pedigree-based study].

OBJECTIVE: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. METHODS: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. RESULTS: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. CONCLUSION: The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

[Casticin inhibits the proliferation, migration and invasion of bladder cancer cells by inhibition of TM7SF4 expression].

Objective: To explore the effect and mechanism of Casticin (CAS) on the proliferation, migration and invasion of bladder cancer T24 cells. Methods: T24 cells were cultured in vitro and divided into control group, 5, 10, 20 µmol/L CAS groups, si-NC group, si-TM7SF4 group, CAS+ pcDNA group and CAS+ pcDNA-TM7SF4 group. Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell was used to detect cell migration and invasion; western blot was used to detect the protein expressions of cyclin D1, p21, MMP-2, MMP-9 and TM7SF4, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of TM7SF4 mRNA. Results: The inhibition rates of T24 cells in the 5, 10, 20 µmol/L CAS groups were (17.68±1.41)%, (33.54±3.16)% and (61.44±5.50)%, respectively, higher than (0.00±0.00)% of the control group (P<0.001), but the numbers of migration and invasion were 72.83±5.66, 59.13±4.27, 41.25±3.22 and 55.83±5.15, 42.19±3.06, 31.13±3.22, respectively, lower than 86.11±5.16 and 68.82±5.29 of the control group (P<0.001). The protein expression levels of cyclin D1, MMP-2, MMP-9, TM7SF4 and the expression levels of TM7SF4 mRNA in the 5, 10, and 20 µmol/L CAS groups were lower than the control group (P<0.001). However, the protein expression levels of p21 were 0.37±0.03, 0.51±0.04, and 0.66±0.06, respectively, higher than 0.25±0.03 in the control group (P<0.001). The inhibition rate of T24 cells in the si-TM7SF4 group was (50.35±4.67)%, higher than (6.31±0.58)% in the si-NC group (P<0.001), but the numbers of migration and invasion were 53.51±4.18 and 42.92±3.81, lower than 85.26±4.99 and 67.93±4.64 of the si-NC group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2, MMP-9 in the si-TM7SF4 group were lower than the si-NC group (P<0.001). However, the protein expression level of p21 in the si-TM7SF4 group was higher than the si-NC group (P<0.001). The inhibitory rate of T24 cells in the CAS+ pcDNA-TM7SF4 group was (21.45±2.46)%, lower than (64.06±4.49)% of the CAS+ pcDNA group (P<0.001), but the number of migration and invasion in the CAS+ pcDNA-TM7SF4 group were 75.66±6.57 and 59.35±5.40, higher than 40.43±3.85 and 30.25±3.32 in the CAS+ pcDNA group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2 and MMP-9 in the CAS+ pcDNA-TM7SF4 group were higher than the CAS+ pcDNA group (P<0.001), but the protein expression level of p21 was lower than the CAS+ pcDNA group (P<0.001). Conclusion: CAS may suppress the proliferation, migration and invasion of bladder cancer T24 cells by inhibiting the expression of TM7SF4.

[Clinical characteristics of coal worker's peneumoconiosis complicated with acute exacerbation of chronic obstractive pulno-mary disease].

Objective: To investigate the clinical characteristics of acute exacerbation of acute lung disease (AECOPD) and to provide reference for clinical diagnosis and treatment. Methods: From January 2018 to December 2018, 127 patients with AECOPD were investigated retrospectively in March 2020, including 65 cases of pneumoconiosis with AECOPD group, 62 cases of AECOPD group, 127 cases of AECOPD group, the clinical characteristics, length of stay, cost difference and the correlation between pulmonary function and blood gas were analyzed in patients with AECOPD. Results: There was no significant difference in age, height, weight, BMI, ethnicity and smoking between the two groups (P>0.05) . The percentage of Neutrophil and hs-crp in pneumoconiosis combined with AECOPD group were significantly higher than those in AECOPD group (P<0.05) . The oxygen partial pressure in pneumoconiosis combined AECOPD group was lower than that in control group (P<0.05) . VC, FVC/Pred%, FEV(1)/Pred% in pneumoconiosis combined with AECOPD group were lower than those in AECOPD group, RV/Pred% and RV/TLC were higher than those in AECOPD group (P<0.05) . The hospitalization time and cost of the patients with AECOPD were significantly higher than that of the patients with AECOPD (P<0.05) . Conclusion: Compared with AECOPD group, the patients with pneumoconiosis combined AECOPD group had higher infection inflammation level, lower pulmonary function, longer hospitalization time and higher hospitalization cost.

Maximizing the security of chaotic optical communications.

The practical application of chaotic optical communications has been limited by two aspects: the difficulty in concealing the time delay - a critical security parameter in feedback chaotic systems, and the difficulty of significantly enlarging the key space without complicating the implementation. Here we propose an architecture to break the above limits. By introducing a frequency-dependent group delay module with frequency tuning resolution of 1 MHz into the chaotic feedback loop, we demonstrate excellent time delay concealment effect, and an additional huge key space of 1048 can be achieved at the same time. The effectiveness is proved by both numerical simulation and experiment. Besides, the proposed scheme is compatible with the existing commercial optical communication systems, thus pave the way for high-speed secure optical communications.

Clinical characteristics and surgical outcome of thoracic myelopathy caused by ossification of the ligamentum flavum: a retrospective analysis of 85 cases.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: To describe the clinical features and radiological findings, to assess the safety and effectiveness of posterior decompressive laminectomy and resection of the ossification of the ligamentum flavum (OLF), and to determine which presurgical and surgical variables were most closely related to postsurgical prognosis of thoracic myelopathy (TM) caused by OLF in China. METHODS: Eighty-five patients with the diagnosis of TM caused by OLF received surgical treatment from July 1998 to May 2012. Clinical data were collected from medical and operative records. Correlations between the surgical outcome and various factors were also analyzed. RESULTS: All cases were followed up for a mean of 49.2 months (range, 24-190 months) postoperatively. The mean Japanese Orthopaedic Association score was 3.8 points preoperatively and 8.2 points at the final follow-up, yielding a mean recovery rate of 63.0%. Postoperative complications included transient neurological deficits (9 cases), persistent neurological deficits (4 cases), dural tears (17 cases), cerebrospinal fluid leakage (9 cases), wound dehiscence (2 cases) and wound infection (3 cases). The OLF level (middle thoracic), preoperative duration of symptoms, intramedullary signal change on T2WI and preoperative severity of myelopathy were important predictors of surgical outcome. CONCLUSIONS: Biomechanical and anatomical factors may have a key role in thoracic OLF progression. Posterior decompressive laminectomy and resection of the OLF can be considered an effective, reliable and safe alternative procedure. The OLF level, preoperative duration of symptoms, intramedullary signal change on T2WI and preoperative severity of myelopathy were confirmed and significantly correlated with the surgical outcome.

MicroRNA-196a promotes cervical cancer proliferation through the regulation of FOXO1 and p27Kip1.

BACKGROUND: The phosphoinositide 3-kinase (PI3K)/Akt signalling pathway appears to be a key regulator in cervical carcinogenesis. However, the downstream regulatory mechanism of PI3K/Akt signalling remains largely unknown. METHODS: The expression of miR-196a in cervical cancer cell lines and cervical cancer tissues was examined using real-time PCR. The effects of miR-196a on PI3K/Akt signalling and cellular proliferation were evaluated by bromodeoxyuridine labelling, 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide, colony formation assays and luciferase assays. RESULTS: The expression level of miR-196a was markedly increased in cervical cancer tissues and cell lines compared with normal cervical tissue and normal cervical squamous cells. Upregulation of miR-196a was correlated with advanced tumour stage and poor overall and recurrence-free survival in cervical cancer patients. Upregulation of miR-196a enhanced G1/S-phase transition and the proliferative ability of cervical cancer cells, whereas suppression of miR-196a had the opposite effect. Using bioinformatics and biological approaches, we showed that FOXO1 and p27(Kip1), two key effectors of PI3K/Akt signalling, were direct targets of miR-196a. CONCLUSIONS: Our findings suggest that miR-196a has an important role in promoting human cervical cancer cell proliferation and may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in cervical cancer.

The treatment of mild cervical spondylotic myelopathy with increased signal intensity on T2-weighted magnetic resonance imaging.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: To compare clinical outcomes of surgery or non-operated treatment for mild cervical spondylotic myelopathy (CSM) patients with intramedullary increased signal intensity (ISI) on T2-weighted imaging (T2WI) of magnetic resonance imaging (MRI), related factors that may affect prognosis were explored. METHODS: Data from 91 patients treated from July 2008 to June 2011 were retrospectively analyzed. The Japanese Orthopedic Association (JOA) recovery ratio was used to compare outcomes of surgery and non-operated treatment. Correlation and multiple linear regression analyses were performed between JOA recovery ratio and age, disease course, segmental lordosis, total range of motion (ROM), segmental ROM, local slip, extent of spinal cord compression or ISI type. RESULTS: Patients were divided into two groups by therapy methods: Group A (n=53, 33 males, age 36-68 years) underwent anterior cervical decompression and fusion surgery, average follow-up 30.68±8.19 months; Group B (n=38, 14 males, age 28-76 years) received non-operated treatment, average follow-up 34.08±9.05 months. There were no significant differences in clinical outcomes between the two groups. There were significant correlations between JOA recovery ratio and clinical course (P<0.01) or segmental lordosis (P<0.01). Patients with shorter disease course and larger segmental lordosis have better clinical outcomes as shown by multiple linear regression analysis. CONCLUSION: For mild CSM patients with ISI on T2WI-MRI, there are no significant differences in clinical outcome between surgery and non-operated treatment during the short-term follow-up. Patients with shorter disease course and larger segmental lordosis have better clinical outcomes than those with longer course and segmental kyphosis.

Effects of rifampicin on osteogenic differentiation and proliferation of human mesenchymal stem cells in the bone marrow.

This study was designed to investigate the effect of different concentrations of rifampicin on osteogenic differentiation and proliferation of mesenchymal stem cells (MSCs) in human bone marrow. Rifampicin treatment at 0, 4, 8, 16, 32, 64, and 128 mg/mL was applied throughout the whole process, from stromal cells purified from human bone marrow to differentiated bone cells. The effect of rifampicin on MSC proliferation was determined using the MTT assay. The effect of rifampicin on the expressions of type I collagen (COL1A1), osteopontin/bone Gla protein (OPN/BGP), and alkaline phosphatase (ALP) in human osteoblast cells were determined by real-time polymerase chain reaction, and the expressions of COL1A1, OPN/BGP, and the runt-related transcription factor (RUNX2) were determined by Western blot. Results showed that the proliferation of MSCs was significantly inhibited when the rifampicin concentration exceeded 32 mg/mL. In addition, increased rifampicin concentrations inhibited the formation of calcium nodules, OPN/BGP, and COL1A1 in osteoblasts after 28 days of induction. The RNA expressions of OPN/BGP, COL1A1, and ALP were significantly downregulated compared to those of the control group in osteoblasts after induction. The protein expressions of RUNX2, COL1A1, and OPN/BGP were also significantly downregulated compared to those of the control group after induction. In conclusion, rifampicin at exorbitant concentration exerts adverse effects on the proliferation of MSCs in human bone marrow and the differentiation of osteoblasts.

An introduction to clinical practice guideline for Chinese undergraduates in stomatology.

The Society of Dental Education, Chinese Stomatological Association has formulated the Standards of Clinical Practice for Chinese Undergraduate Students Majoring in Stomatology, on the basis of extensively soliciting the views of experts in various fields. The aim of this standard is to guide clinical teaching and improve teaching quality in schools of stomatology in China. The standards include eight parts: the standard of clinical practice for oral and maxillofacial surgery, for cariology and endodontics, for periodontics, for the oral mucosa diseases, for preventive dentistry, for pedodontology, for prosthodontics and for oral imageology. Each part includes introduction to subjects, the clinical practice time period, the purpose and requirements of practice, the disease types of practice and items of clinical operation, the index of the lowest workload of practice and the major methods of assessment. These standards are not only the basic requirements and guiding principles for clinical teaching, but also the major criteria for assessing the clinical teaching quality of stomatological colleges/schools of China.

[Teriparatide regulates osteoblast differentiation in high-glucose microenvironment through the cAMP/PKA/CREB signaling pathway].

OBJECTIVE: To investigate the effect of teriparatide on the differentiation of MC3T3-E1 cells in high-glucose microenvironment and explore the possible mechanism. METHODS: MC3T3-E1 cells cultured in normal glucose or high-glucose (25 mmol/L) medium were treated with 10 nmol/L teriparatide with or without co-treatment with H-89 (a PKA inhibitor). CCK-8 assay was used to detect the changes in cell proliferation, and cAMP content in the cells was determined with ELISA. Alkaline phosphatase (ALP) activity and mineralized nodules in the cells were detected using ALP kit and Alizarin red staining, respectively. The changes in cell morphology were detected by cytoskeleton staining. Real-time PCR was used to detect the mRNA expressions of PKA, CREB, RUNX2 and Osx in the treated cells. RESULTS: The treatments did not result in significant changes in proliferation of MC3T3-E1 cells (P > 0.05). Compared with the cells in routine culture, the cells treated with teriparatide showed significantly increased cAMP levels (P < 0.05) with enhanced ALP activity and increased area of mineralized nodules (P < 0.05). Teriparatide treatment also resulted in more distinct visualization of the cytoskeleton in the cells and obviously up-regulated the mRNA expressions of PKA, CREB, RUNX2 and Osx (P < 0.05). The opposite changes were observed in cells cultured in high glucose. In cells exposed to high glucose, treatment with teriparatide significantly increased cAMP levels (P < 0.05), ALP activity and the area of mineralized nodules (P < 0.05) and enhanced the clarity of the cytoskeleton and mRNA expressions of PKA, CREB, RUNX2 and Osx; the effects of teriparatide was strongly antagonized by co-treatment with H-89 (P < 0.05). CONCLUSION: Teriparatide can promote osteoblast differentiation of MC3T3-E1 cells in high-glucose microenvironment possibly by activating the cAMP/PKA/CREB signaling pathway.

[The role of the high-level public health school in the development of the Center for Disease Control and Prevention].

The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.

Insulin Resistance-Varying Associations of Adiposity Indices with Cerebral Perfusion in Older Adults: A Population-Based Study.

OBJECTIVES: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance. DESIGN: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study. SETTING AND PARTICIPANTS: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans. METHODS: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis. RESULTS: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted ß-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05). CONCLUSION: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging.

New evaluation of the thermodynamics stability for bcc-Fe.

The thermodynamic properties for bcc-Fe were predicted by combination of the first-principles calculations, the quasiharmonic approximation, the CALPHAD method and the Weiss molecular field theory. The hybrid method considers the effects of the lattice vibration, electron, intrinsic magnetism and external magnetic fields on the thermodynamic properties at finite temperature. Combined with experimental data, the calculated heat capacity without external magnetic fields was used to verify the validity of the hybrid method. Close to the Fermi level the high electronic density of states leads to a significant electronic contribution to free energy. Near the Curie temperature lattice vibrations dominant the Gibbs free energy. The order of the other three excitation contributions to Gibbs free energy from high to low is: intrinsic magnetism > electron > external magnetic fields. The investigation suggests that all the excitation contributions to Gibbs free energy are not negligible which provides a correct direction for tuning the thermodynamic properties for Fe-based alloy.

[Analysis on off-label use of drugs in pediatric guidelines and consensus published by Chinese authors].

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.

Computed tomographic angiography study of the relationship between the lingual artery and lingual markers in patients with obstructive sleep apnoea.

AIM: To determine the relationship between the lingual artery and lingual markers for preoperative evaluation of the lingual artery in patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS). METHODS: A 16-section computed tomographic angiography (CTA) of the lingual artery was performed in 87 inpatient cases with OSAHS, from December 2007 to May 2009. The course of the lingual artery and the anatomic relationship between the lingual artery and the lingual markers were analyzed using CTA imaging. RESULTS: The course of the lingual artery with the tongue in a resting position was similar to that of the Big Dipper constellation (Plough) in the sagittal view of CTA imaging. The first segment of the lingual artery declined approximately 19.27 ± 5.24 mm, the middle segment of the lingual artery was forward approximately 19.30 ± 6.79 mm, and the ascending segment of the lingual artery rose approximately 52.49 ± 10.98 mm. The entry point where the lingual artery entered into the tongue was adjacent to the tip of the greater horn of the hyoid bone. The relationship between the second segment of the lingual artery and the greater horn of the hyoid bone was relatively steady with the tongue in whatever position. The interval between the bilateral greater horn of the hyoid bone equalled that between the bilateral lingual arteries. CONCLUSIONS: Recognizing some lingual markers in the patients with OSAHS, such as the greater horn of the hyoid bone, foramen cecum, circumvallate papilla, lingual vein and tongue midline, may facilitate the surgeon's ability to define the course of the lingual artery accurately in the treatment of OSAHS.

[Expression profile of intervertebral disc degeneration-specific genes: a transcriptome sequencing-based analysis].

OBJECTIVE: To identify new therapeutic targets for intervertebral disc degeneration (IDD) by analyzing gene variations in IDD. OBJECTIVE: We analyzed surgical samples of intervertebral disc from 4 patients with IDD and 3 patients with non-IDD using RNA sequencing (RNA-seq) technology to identify significant differentially expressed genes (DEGs) in IDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for gene enrichment studies to acquire the key genes and signal pathways during IDD progression. The differential expressions of the identified genes in IDD were validated in clinical samples with qRT-PCR. OBJECTIVE: The transcriptome profile revealed 512 significant DEGs, which were enriched in terms of keratinization, extracellular matrix (ECM) components, growth factor binding, and inflammatory chemotaxis in GO analysis. The top 10 terms of KEGG enrichment included amoebiasis, viral protein interaction with cytokine and cytokine receptor, ECM-receptor interaction, IL-17 signaling pathway, cytokine-cytokine receptor interaction, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, chemokine signaling pathway and estrogen signaling pathway. Thirteen DEGs selected as the targets for qRT-PCR validation showed significant differential expressions in IDD (P < 0.001), and their expression trends were all consistent with the results of RNA-seq. Among these genes, 10 genes showed significant intergroup fold change (Log2FoldChange>1). OBJECTIVE: ECM, growth factors, collagen components, inflammatory chemokines and such signal pathways as TNF-α and PI3K-Akt all have important contributions to IDD progression and may thus serve as new therapeutic targets for treatment of IDD.

Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.

Colloidal dispersion stability of CuPc aqueous dispersions and comparisons to predictions of the DLVO theory for spheres and parallel face-to-face cubes.

The dispersion stability and the zeta potentials of nonspherical crystalline (beta-form) copper phthalocyanine (CuPc) particles of hydrodynamic diameter d(h) approximately = 90 nm were investigated at 25 degrees C in water and in aqueous solutions of NaNO(3). The electrolyte concentrations c ranged from 1 to 500 mM and the particle concentrations ranged from 50 to 10,000 ppm (0.005 to 1 wt %). In each case, the Fuchs-Smoluchowski stability ratio W was determined from dynamic light scattering (DLS) data and the Rayleigh-Debye-Gans (RDG) scattering theory. The data suggest that electrostatic effects play a major role in the stability of CuPc-based dispersions. The calculated particle charge z per CuPc particle based on the zeta potential data and the area of the particles (assumed to be cubical) suggests that there is preferential adsorption of NO(3)(-) ions on the uncharged CuPc surface, and the surface charge increases with increasing electrolyte concentration. Furthermore, two new models of the DLVO theory, for spheres and for parallel face-to-face cubes, were reformulated in dimensionless form. The Hamaker constant of CuPc particles was calculated by the same authors on the basis of theoretical models in J. Chem. Theory Comput. (2010, in press). The key dimensionless group is the ratio N of the electrostatic double layer energy to the Hamaker constant. The two DLVO models were used to predict the value of a dimensionless maximum potential energy Phi(max), the conditions when it may exist, and then the value of W. In water, the DLVO model for spheres overpredicted the stability, while the model for cubes underpredicted the stability. At c = 1 mM, both models overpredicted the stability. At c = 10 mM, the model for spheres underpredicted the stability, whereas the model for cubes overpredicted the stability. Hence, there seems to be some significant shape effects on the electrostatic stabilization of CuPc particle dispersions. At c = 100 and 500 mM, both models underpredicted the stability substantially, suggesting the existence of additional short-range repulsive forces, which may primarily control the stability. Simple sensitivity analysis on the calculations supported these conclusions.

GPAA1 promotes progression of childhood acute lymphoblastic leukemia through regulating c-myc.

OBJECTIVE: Previous studies have shown that glycosylphosphatidylinositol Anchor Attachment Protein 1 (GPAA1) is a cancer-promoting gene; however, the role of GPAA1 in childhood acute lymphoblastic leukemia (ALL) has not been reported. This study aims to illustrate the role of GPAA1 in promoting the metastasis of ALL by targeting c-myc and the potential mechanism. PATIENTS AND METHODS: Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to examine serum levels of GPAA1 and c-myc in 42 childhood ALL patients and healthy volunteers. The interaction between GPAA1 expression and prognosis of childhood ALL was analyzed. Meanwhile, expressions of GPAA1 and c-myc in ALL cell lines were determined by qRT-PCR. Furthermore, after GPAA1 knockdown model was constructed by lentivirus transfection in MOLT-4 and SUP-B15 cells, cell counting kit-8 (CCK-8), transwell invasion, and cell wound healing assays were conducted to analyze the effect of GPAA1 on the biological functions of ALL cells. Potential mechanism was further explored through Luciferase reporter gene assay and cell recovery experiments. RESULTS: QRT-PCR results indicated that serum level of GPAA1 in childhood ALL patients was remarkably higher than that of healthy volunteers, and the difference was statistically significant. Childhood ALL patients with high expression of GPAA1 had lower overall survival rate compared with those expressing low expression of GPAA1. Proliferation and metastasis abilities of pediatric ALL cells with GPAA1 knockdown remarkably decreased. Subsequently, c-myc expression was also found remarkably upregulated in ALL cell lines and serum samples of childhood ALL patients and it was positively correlated with GPAA1 level. In addition, Luciferase reporter gene assay demonstrated that overexpression of c-myc remarkably attenuated the Luciferase activity of the wild-type GPAA1 vector without attenuating that of the mutant vector or empty vector, further demonstrating that GPAA1 can be targeted by c-myc. At the same time, cell recovery experiment found that the interaction between GPAA1 and c-myc together regulated the malignant progression of ALL. CONCLUSIONS: GPAA1 was up-regulated in serum of childhood ALL patients, which was remarkably associated with the prognosis. In addition, GPAA1 may contribute to the malignant progression of childhood ALL via activating c-myc.

Locomotor transition: how squid jet from water to air.

The amazing multi-modal locomotion of flying squid helps to achieve fast-speed migration and predator-escape behavior. Observation of flying squid has been rarely reported in recent years, since it is challenging to clearly record the flying squid's aquatic-aerial locomotion in a marine environment. The existing reports of squid-flying events are rare and merely record the in-air motion. Therefore, the water-air locomotor transition of flying squid is still unknown. This paper proposes the idea of using CFD to simulate the process of the flying squid (Sthenoteuthis oualaniensis (S. oualaniensis)) launching from water into air. The results for the first time reveal the flow field information of squid in launching phase and show the kinematic parameters of flying squid in quantification. Both a trailing jet and pinch-off vortex rings are formed to generate launching thrust, and the formation number L ω /D ω is 5.22, demonstrating that the jet strategy is to produce greater time-averaged thrust rather than higher propulsion efficiency. The results also indicate that the maximum flying speed negatively correlates with the launch angle, indicating that a lower launch angle could result in a larger flying speed for the flying squid to escape. These findings explore the multi-modal locomotion of flying squid from a new perspective, helping to explain the trade-off strategy of water-to-air transition, and further enhance the performance of aquatic-aerial vehicles.