Interfacial Organization and Forces Arising from Epithelial-Cancerous Monolayer Interactions.

The interfacial interactions between epithelia and cancer cells have profound relevance for tumor development and metastasis. Through monolayer confrontation of MCF10A (nontumorigenic human breast epithelial cells) and MDA-MB-231 (human epithelial breast cancer cells) cells, we investigate the epithelial-cancerous interfacial interactions at the tissue level. We show that the monolayer interaction leads to competitive interfacial morphodynamics and drives an intricate spatial organization of MCF10A cells into multicellular finger-like structures, which further branch into multiple subfinger-like structures. These hierarchical interfacial structures penetrate the cancer monolayer and can spontaneously segregate or even envelop cancer cell clusters, consistent with our theoretical prediction. By tracking the substrate displacements via embedded fluorescent nanobeads and implementing nanomechanical modeling that combines atomic force microscopy and finite element simulations, we computed mechanical force patterns, including traction forces and monolayer stresses, caused by the monolayer interaction. It is found that the heterogeneous mechanical forces accumulated in the monolayers are able to squeeze cancer cells, leading to three-dimensional interfacial bulges or cell extrusion, initiating the p53 apoptosis signaling pathways of cancer cells. We reveal that intercellular E-cadherin and P-cadherin of epithelial cells differentially regulate the interfacial organization including migration speed, directionality, spatial correlation, F-actin alignment, and subcellular protrusions of MCF10A cells; whereas E-cadherin governs interfacial geometry that is relevant to force localization and cancer cell extrusion, P-cadherin maintains interfacial integrity that enables long-range force transmission. Our findings suggest that the collaborative molecular and mechanical behaviors are crucial for preventing epithelial tissues from undergoing tumor invasion.

Mechanically sensitive HSF1 is a key regulator of left-right symmetry breaking in zebrafish embryos.

The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer's vesicle of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation by mechanical clues during embryonic development and other physiological and pathological transformations.

Collective Polarization of Cancer Cells at the Monolayer Boundary.

Cell polarization, a process depending on both intracellular and intercellular interactions, is crucial for collective cell migration that commonly emerges in embryonic development, tissue morphogenesis, wound healing and cancer metastasis. Although invasive cancer cells display weak cell-cell interactions, they can invade host tissues through a collective mode. Yet, how cancer cells without stable cell-cell junctions polarize collectively to migrate and invade is not fully understood. Here, using a wound-healing assay, we elucidate the polarization of carcinoma cells at the population level. We show that with loose intercellular connections, the highly polarized leader cells can induce the polarization of following cancer cells and subsequent transmission of polarity information by membrane protrusions, leading to gradient polarization at the monolayer boundary. Unlike the polarization of epithelial monolayer where Rac1/Cdc42 pathway functions primarily, our data show that collective polarization of carcinoma cells is predominantly controlled by Golgi apparatus, a disruption of which results in the destruction of collective polarization over a large scale. We reveal that the Golgi apparatus can sustain membrane protrusion formation, polarized secretion, intracellular trafficking, and F-actin polarization, which contribute to collective cancer cell polarization and its transmission between cells. These findings could advance our understanding of collective cancer invasion in tumors.

Universal Statistical Laws for the Velocities of Collective Migrating Cells.

Migratory dynamics of collective cells is central to the morphogenesis of biological tissues. The statistical distribution of cell velocities in 2D confluent monolayers is measured through large-scale and long-term experiments of various cell types lying on different substrates. A linear relation is discovered between the variability and the mean of cell speeds during the jamming process of confluent cell monolayers, suggesting time-invariant distribution profile of cell velocities. It is further found that the probability density function of cell velocities obeys the non-canonical q-Gaussian statistics, regardless of cell types and substrate stiffness. It is the Tsallis entropy, instead of the classical Boltzmann-Gibbs entropy, that dictates the universal statistical laws of collective cell migration. The universal statistical law stems from cell-cell interactions, as demonstrated by the wound healing experiments. This previously unappreciated finding provides a linkage between cell-level heterogeneity and tissue-level ensembles in embryonic development and tumor growth.

Health Communication Through News Media During the Early Stage of the COVID-19 Outbreak in China: A Digital Topic Modeling Approach

BackgroundIn December 2019, some COVID-19 cases were first reported and soon the disease broke out. As this dreadful disease spreads rapidly, the mass media has been active in community education on COVID-19 by delivering health information about this novel coronavirus. MethodsWe adopted the Huike database to extract news articles about coronavirus from major press media, between January 1st, 2020, to February 20th, 2020. The data were sorted and analyzed by Python software and Python package Jieba. We sought a suitable topic number using the coherence number. We operated Latent Dirichlet Allocation (LDA) topic modeling with the suitable topic number and generated corresponding keywords and topic names. We divided these topics into different themes by plotting them into two-dimensional plane via multidimensional scaling. FindingsAfter removing duplicates, 7791 relevant news reports were identified. We listed the number of articles published per day. According to the coherence value, we chose 20 as our number of topics and obtained their names and keywords. These topics were categorized into nine primary themes based on the topic visualization figure. The top three popular themes were prevention and control procedures, medical treatment and research, global/local social/economic influences, accounting for 32{middle dot}6%, 16{middle dot}6%, 11{middle dot}8% of the collected reports respectively. InterpretationThe Chinese mass media news reports lag behind the COVID-19 outbreak development. The major themes accounted for around half the content and tended to focus on the larger society than on individuals. The COVID-19 crisis has become a global issue, and society has also become concerned about donation and support as well as mental health. We recommend that future work should address the mass medias actual impact on readers during the COVID-19 crisis through sentiment analysis of news data. FundingNational Social Science Foundation of China (18CXW021) Evidence before this studyThe novel coronavirus related news reports have engaged public attention in China during the COVID-19 crisis. Topic modeling of these news articles can produce useful information about the significance of mass media for early health communication. We searched the Huike database, the most professional Chinese media content database, using the search term "coronavirus" for related news articles published from January 1st, 2020, to February 20th, 2020. We found that these articles can be classified into different themes according to their emphasis, however, we found no other studies apply topic modeling method to study them. Added value of this studyTo our knowledge, this study is the first to investigate the patterns of health communications through media and the role the media have played and are still playing in the light of the current COVID-19 crisis in China with topic modeling method. We compared the number of articles each day with the outbreak development and identified theres a delay in reporting COVID-19 outbreak progression for Chinese mass media. We identify nine main themes for 7791 collected news reports and detail their emphasis respectively. Implications of all the available evidenceOur results show that the mass media news reports play a significant role in health communication during the COVID-19 crisis, government can strengthen the report dynamics and enlarge the news coverage next time another disease strikes. Sentiment analysis of news data are needed to assess the actual effect of the news reports.

The tolerance to 188Re-HEDP treatment in patients with bone pain from osseous metastases / 中华核医学杂志

Objective To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate(HEDP) in patients with bone pain caused by osseous metastases. Methods Thirty-one patients(10with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade Ⅲ- Ⅳ was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg.No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade Ⅰ leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade Ⅰ leucopenia including 1 alone with reversible grade Ⅲ thrombopenia. In the 40 MBq/kg group, reversible grade Ⅰ leucopenia and thrombopenia was observed in 1 patient and reversible grade Ⅱ leucopenia and thrombopenia in another patient. In the .50 MBq/kg group, 3 patients showed reversible grade Ⅱ leucopenia. The lowest level of thrombopenia was at week 4(143.5 × 109/L), leucopenia at week 6 (5.4 × 109/L) and anaemia at week 8(t = 3.1325, 3.3156, 3.4917, all P ＜ 0. 05 compared with baseline). At week 8, the mean level of platelet and leucocyte recovered to baseline. "Bounce pain" was found in 2 of 27 patients (7.41%).Conclusions The dose of 20 MBq/kg, 30 MBq/kg, 40 MBq/kg or 50 MBq/kg of 188Re-HEDP do not cause significant side effects on cancer patients with bone metastases, though there is a tendency that the haematological toxicity may increase as the dose of 188Re-HEDP increases.

Evaluation of mycolic acid analysis in identification of Mycobacterium species through SMIS / 中华检验医学杂志

Objective To evaluate the usefulness of mycolic acid for identification of Mycobacterium species using SMIS. Methods One hundred and eighteen clinical Mycobacterium isolates collected from Beijing Tuberculosis and Thoracic Tumor Research Institute through whole year of 2007 were analyzed. The 118 isolates contain 25 isolates of Mycobacterium tuberculosis and 93 non tuberculosis Mycobacterium identified by PNB method. Mycolic acid analysis using SMIS is evaluated for identification of a broad range of Mycobacteria in comparison with 16S rDNA , 16-23S rDNA ITS sequencing to measure the concordance rate and agreement, and verify the concordance rate and agreement among results of mycolic acid, sequencing and PNB in identifying Mycobacterium tuberculosis and non tuberculosis Mycobacterium. Results The concordance rate between mycolic acid method analysis and DNA sequencing is 92% ( 108/118), of which concordance rate in Mycobacterium tuberculosis complex and non tuberculosis Mycobacterium are 95% (35/37) and 90% (73/81) respectively, agreement of both is great( agreement Kappa value is 0. 96). Through retrospective analysis, the concordance of results between SMIS and PNB method analysis is 90% (106/118)and agreement is well( agreement Kappa value is 0. 73 ), the concordance of results between sequencing and PNB method analysis is also 90% ( 106/118 ) and agreement is well (agreement Kappa value is 0. 74 ),despite the identification results of 11 isolates by PNB method are discordant. Conclusion Mycolic acid analysis by SMIS enables rapid identification of a broad range of clinical Mycobacterium species, which could play an important role in polyphasic identification of Mycobacterium species.

Genotyping and drug resistance analysis of Mycobacterium tuberculosis from China / 中华检验医学杂志

Objective To study the genotypes of representative Mycobacterium tuberculosis (M.tuberculosis) strains from China with spacer oligonucleotide typing (spoligotyping),and to investigate the prevalence of different genotypes TB in China,and analyse the relationship between genotype and drug resistance.Methods 4017 clinical isolates were collected by Chinese Center for Disease Control and Prevention from 2007 to 2008 in 31 provinces in China according to sampling principle of epidemiology.Drug susceptibility testing was performed using proportion method,and spoligotyping was chosen to carry out genotyping of these M.tuberculosis.In addition,chi-square test was used to compare the differences among the detection rate of different genotypes.Results Among the 4017 M.tuberculosis isolates,2500 ( 62.2％ ) isolates belonged to Beijing genotype.The percentage of Beijing genotypes in the northern of China was higher than that in the southern of China ( 76.5％ vs.53.2％,x2 =219.69,P ＜ 0.05 ),while T1 genotypes were more common in the southern China,compared with that in northern China ( 13.3％ vs.4.3％,x2 =219.69,P ＜ 0.05 ).The differences were statistically significant.The proportions of Rifampinresistant (21.7％ vs.21.7％ ),Ofloxacin-resistant (4.9％ vs.2.4％ ) and Multidrug-resistant ( 11.3％vs.7.4％ ) isolates among Beijing genotype strains were significantly higher than those among non-Beijing strains (x2 =22.10,14.42 and 14.83,respectively,P ＜ 0.05 ).Conclusions Beijing genotype was still predominant epidemic genotypes.The percentage of Beijing genotype showed difference between distinct areas,and the percentage of Beijing genotypes in northern China was higher than that in southern China.Beijing genotype strains reveal correlation with Rifampin-resistance,Ofloxacin-resistance and Multidrug-resistance.

Investigation of the frequency shift of a SAD circuit loop and the internal micro-cantilever in a gas sensor.

Micro-cantilever sensors for mass detection using resonance frequency have attracted considerable attention over the last decade in the field of gas sensing. For such a sensing system, an oscillator circuit loop is conventionally used to actuate the micro-cantilever, and trace the frequency shifts. In this paper, gas experiments are introduced to investigate the mechanical resonance frequency shifts of the micro-cantilever within the circuit loop(mechanical resonance frequency, MRF) and resonating frequency shifts of the electric signal in the oscillator circuit (system working frequency, SWF). A silicon beam with a piezoelectric zinc oxide layer is employed in the experiment, and a Self-Actuating-Detecting (SAD) circuit loop is built to drive the micro-cantilever and to follow the frequency shifts. The differences between the two resonating frequencies and their shifts are discussed and analyzed, and a coefficient α related to the two frequency shifts is confirmed.

Cerebral blood flow and related factors in hyperthyroidism patients by SPELT imaging and statistical parametric mapping analysis / 中华核医学杂志

Objective To investigate the cerebral blood flow (CBF) perfusion patterns and related factors in hyperthyroidism patients.Methods Twenty-five patients with hyperthyroidism and twenty-two healthy controls matched for age,sex,education were enrolled.~(99)Tc~m-ethylene cysteinate dimer (ECD) SPECT CBF perfusion imaging was performed at rest.Statistical parametric mapping 5.0 software (SPM5) was used and a statistical threshold of P＜0.05 (corrected) was applied for signifying changes of regional CBF (rCBF).The semiquantitative values of rCBF were extracted automatically by brain search 1.1 software and were correlated with concentrations of serum thyroid hormones(FT_3,FT_4),thyroid autoimmune antibodies:sensitive thyroid stimulating hormone(sTSH),thyroid peroxidase antibody (TPOAb) and TSH receptor antibody (TRAb) by Pearson analysis,with disease duration by Spearman analysis.Results rCBF was decreased significantly in limbic system and frontal lobe,including parahippocampal gyrus,uncus (posterior entorhinal cortex,posterior parolfactory cortex,parahippocampal cortex,anterior cingulate,right inferior temporal gyrus),left hypothalamus and caudate nucleus (P＜0.05,corrected).rCBF in left lingual gyrus,posterior cingulated was negatively correlated with concentration of FT_3(r=-0.468,-0.417,both P＜0.05).rCBF in left lingual gyrus,bilateral inferior temporal gyrus,right superior parietal lobe was negatively correlated with concentration of FT_4(r=-0.4M,-0.418,-0.415,-0.459,all P＜0.05),while that in left mammillary body and putamen was positively correlated with concentration of FT_4(r=0.419,0.412,both P＜0.05).rCBF in left insula was negatively correlated with concentration of sTSH,and right auditory associated cortex was positively correlated with concentration of sTSH(r=-0.504,0.429,both P＜0.05).rCBF in left middle temporal gyrus,left angular gyrus was positively correlated with concentration of TRAb while that in right thalamus,right hypothalamus,left anterior nucleus,left ventralis nucleus was negatively correlated with concentration of TRAb(r=0.750,0.862,-0.691,-0.835,-0.713,-0.759,all P＜0.05).rCBF in right anterior cingulate,right cuneus,right rectus gyrus,right superior marginal gyrus was positively correlated with concentration of TPOAb(r=0.696,0.581,0.779,0.683,all P＜0.05).rCBF in postcentral gyrus,temporal gyrus,left superior marginal gyrus and auditory associated cortex was positively correlated with disease duration(r=0.502,0.457,0.524,0.440,all P＜0.05).Conclusion Hypoperfusions in limbic system and fontal lobe were found in hyperthyroidism Patients,which might be associated with thyroid function and disesse duration.

Clinical curative effect of combination between medicine and acupoint flow on SOD, NO in patients with ulcerative colitis / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the clinical curative effect of the combination between medicine and acupoint flow on SOD, NO in patients with ulcerative colitis.</p><p><b>METHOD</b>Two hundred sixty two patients with ulcerative colitis were randomly divided into four groups: the patients in traditional Chinese medicine group were fed with changpikang, the patients in ear acupoint group were pasted and pressed spleen, large intestine, sympathesis, subcortex; the patients in medicine and acupoint group were taken with Changpikang and ear acupoint; the patients in treatment group were treated by taking sulfasalazine, with a treatment course of four weeks. The changes of SOD, NO before and after treatments were recored.</p><p><b>RESULT</b>There was a significant difference between four groups before and after treatment (P < 0.05), medicine and acupoint group was superior to that others (P < 0.05).</p><p><b>CONCLUSION</b>The method of combination between medicine and acupoint could increase the contents of SOD, decrease the level of NO, elevate the potential of organism to resist oxygen free radical and promote intestinal tract ulcer concrescence.</p>

Intracavitary hyperthermia combined with radiochemotherapy for esophageal carcinoma / 中国癌症杂志

Hyperthermia can enhance the sensitivity of tumors to radiotherapy and chemotherapy, In order to understand the impact of intracavitary hyperthermia on radiochemotherapy in esophageal carcinoma, the biological basis,advances,efficacy and active factors of intracavitary hyperthermia combined with radiochemotherapy in esophageal carcinoma is reviewed and evaluated.

A clinical study in undifferentiated small cell carcinoma of the esophagus / 中国癌症杂志

Background and purpose:Esophageal cancer(EC) is one of the most common cancers that account for cancer-related deaths and over 400,000 new cases has been diagnosed per year.The morbility of small cell carcinoma of the esophagus(SCEC) is very low.This paper was to study was the clinical characteristics,treatment and prognosis of undifferentiated small cell carcinoma of the esophagus(SCEC).Methods:From 1961 to 2003,743 patients with SCEC were treated in different hospitals.The number of small cell carcinoma of the esophagus seen accounted for 1.38% of esophageal cancer treated in those hospitals in the same period.the average age was 56.8(range,51 to 66).511 of patients were male and 232 female.2 of them had primary tumor in the cervical proportion of the esophagus,68 in the upper thoracic proportion,420 in the mid thoracic proportion,252 in the lower proportion and 1 in the whole esophagus.88 patients were treated by surgery alone,23 by radiotherapy alone,24 patients by chemotherapy alone and all other of patients were treated by combined modality.Results:The median survival was 12.4 months for all patients,with 10.8 months for surgery,6.2 months for radiotherapy,6.6 months for chemotherapy,14.7 months for surgery combined with radiotherapy,16.1 months for surgery combined with chemotherapy,12.3 months for chemoradiotherapy and 16.2 months for surgery combined with chemoradiotherapy,respectively.The survival rates at 1,2,3,4,and 5 years were 56.4%、27%、19.3%、11.1%、(9.7%) for the whole group,respectively.Conclusions:We recommend that combined modality should be used for SCEC.The combination of surgery and multi-drug chemotherapy may improve the treatment outcomes for the patients with early stage SCEC.

Late course accelerated hyperfractionated irradiation combined with intraluminal hyperthermia for esophageal carcinoma / 中华放射肿瘤学杂志

Objective To evaluate the effect of late course accelerated hyperfractionated irradiation combined with intraluminal hyperthermia for esophageal carcinoma. Methods From March 2000 to October 2002, totally 91 such eligible patients were entered into the prospective randomized control trial of late course accelerated hyperfractionated irradiation (LCAH-, 44 patients) versus LCAH combined with intraluminal hyperthermia ( LCAH-HT-, 47 patients). Radiotherapy regimen consisted of conventional fractionation radiotherapy (1.8 ?Gy/f, 5f/w, totally 41.4 ?Gy/23fx) during the first two-thirds of the radiotherapy course, followed by accelerated hyperfractionation radiotherapy (1.5?Gy/f, 2f/d, with 6 h interval), using the cone-down fields, to a total dose of 68.4?Gy/41fx . Hyperthermia was given weekly during conventional fractionation irradiation, totally 4 times. Results The CR and PR rates were 47.7% and 72.3%, 52.3%and 27.8% in the LCAH arm and LCAH-HT group,respectively(P=0.016). The median survivals were 30.3 and 30.6 months,the 1-,2-,3-year survival rates were 77.3%,57.4% ,37.3% and 80.5%,68.6%, 46.3%(P= 0.526 ), the 1-,2-,3-year local control rates were 86.3%,70.5%,56.5% and 92.4%,72.5%,65.5% (P= 0.686 )in the LCAH group and LCAH-HT group,respectively. Grade III and severer of esophagitis were 18.2% and 27.6% in LCAH and LCAH-HT (P= 0.498 ), Grade III and severer tracheitis were 11.4% and 19.2% respectively (P=0.191). Conclusions The immediate effect of LCAH combined with hyperthermia is better than that of LCAH alone. Additional hyperthermia to LCAH does not increase the likelihood of radiation injury.