[Influence of Social Capital on the Life Quality of Patients with Chronic Diseases-A Study Based on EQ-5D-5L Scale].

OBJECTIVE: To explore the influence of social capital on the quality of life of patients with chronic non-communicable diseases. METHODS: A multi-phase stratified cluster sampling method was adopted to select the survey respondents. Professionally trained surveyors made home visits in order to conduct face-to-face questionnaire surveys in person. European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) and a self-developed social capital scale were used to investigate the quality of life and social capital of the respondents. Factor analysis and Cronbach's α coefficient test were done to verify the reliability and validity of the self-developed social capital scale. The χ 2 test and robust Tobit regression model were used to analyze the impact of social capital on the quality of life of patients with chronic non-communicable diseases. RESULTS: The self-developed social capital scale showed excellent performance. The Cronbach's α coefficient was 0.728, the KMO value was 0.716, and the result of Bartlett's test of sphericity was statistically significant ( P<0.001), indicating that the data were well suited for factor analysis. The four common factors cumulatively explained 68.27% of the total variation. The health utility value of the survey respondents was 0.869±0.181. Those who could walk around, shower and dress themselves, and perform usual activities without any problem accounted for 75.70%, 80.10%, and 74.1% of the respondents, respectively. Those who had pain or discomfort and anxiety or depression, with no self-perceived problem were 43.40% and 58.90%, respectively. In the EQ-5D-5L scale, the self-rated health influencing factors of the physical health dimension were community safety and interpersonal network relationships. The influencing factors of social function health was community safety and mental health was affected by community safety, community trust and interpersonal network relationships. When community safety improved by one level, the health utility value of patients with chronic non-communicable diseases increased by 0.046, and when interpersonal network relationships improved by an additional level, their health utility value increased by 0.037. CONCLUSION: The main problem of the quality of life of patients with chronic non-communicable diseases was found in the mental health dimension. In the process of treating chronic non-communicable diseases, attention should also be given to psychological counseling. Community safety and interpersonal network relationships are the protective factors for self-rated health status. Providing a safe community environment and expanding interpersonal networks help improve the health of patients.

[Analysis of the Status of Depression and the Influencing Factors in Middle-Aged and Older Adults in China].

OBJECTIVE: To understand the status of depression and its influencing factors in the middle-aged and older adult populations aged 45 and above in China on the basis of data from the 2018 China Family Panel Studies (CFPS), and to provide empirical evidence for the improvement of the mental health of the middle-aged and older adults and the alleviation of their depressive symptoms. METHODS: The source of the research data was the 2018 CFPS. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess the prevalence of depression. A two-level two-category unconditional logistics regression method was used to analyze the influencing factors of the prevalence of depressive symptoms. RESULTS: The 80th percentile interval score of depression score was used as the critical value, and the detection rate of depressive symptoms was 23.61%. It was more likely for women to suffer from depressive symptoms than it was for men. Widowed individuals were at an even higher risk for having depression. The more education one had, the lower the possibility of developing depression. Middle-aged and older adults in rural areas were more likely to suffer from depression. Middle-aged and older adults with chronic diseases and self-rated poor health were at higher risk of depression. Sleep time is a protective factor that suppressed symptoms. After controlling the above-mentioned individual-level factors, middle-aged and older adults in coastal and economically developed areas were less likely to suffer from depression than those from inland and economically underdeveloped areas did. CONCLUSION: The health departments concerned should focus on the depressive symptoms of women, widowed individuals, and middle-aged and older adults with chronic diseases. In rural areas and underdeveloped inland regions, the state should invest more health resources in the prevention and improvement of depression among middle-aged and older adults.

[Evaluation of Reliability and Validity of EQ-5D-5L Based on Residents in Southwest China].

OBJECTIVE: To explore the reliability and validity of the EQ-5D-5L scale in the population of southwest China. METHODS: The internal consistency reliability is measured by Cronbach's α coefficient and the structural validity is measured by factor analysis. The difference in health utility value of different characteristic populations is compared by t test and analysis of variance. RESULTS: Cronbach's α coefficient was 0.857. Exploratory factor analysis extracts two common factors whose cumulative contribution rate is 77.311%. The first common factor represents mobility, self-care and uaual activities. The second common factor represents pain/discomfort and anxiety/depression. The results of confirmatory factor analysis showed that the correlation of the two common factors was 0.659, the average variance of the first common factor was 0.862 and the combination reliability was 0.949, and the average variance extracted of the second common factor was 0.587 and the composite reliability was 0.739. The factor loadings for mobility, self-care and uaual activities on the first common factor were 0.871, 0.945 and 0.967, respectively. The loadings for pain/discomfort and anxiety/depression on the second common factor were 0.708 and 0.820, respectively. CONCLUSION: EQ-5D-5L has good reliability and validity when it is applied to the measurement of healthy life quality of residents in Southwest China.

Perinatal polychlorinated biphenyls and polychlorinated dibenzofurans exposure are associated with DNA methylation changes lasting to early adulthood: Findings from Yucheng second generation.

Epigenome-wide DNA methylation has not been studied in men perinatally exposed to PCBs and dioxins. Therefore, we examined whether perinatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) induces sustained methylation changes lasting to early adulthood. We used the Illumina HumanMethylation450 BeadChip to assess DNA methylation in whole blood among Yucheng second generation (people perinatal exposed to high PCBs and PCDFs) compared with referents. Thirty male offspring from the Yucheng cohort were randomly selected and matched with 30 male offspring from the Yucheng' neighborhood referents with similar backgrounds. Methylation differences between the Yucheng second generation and non-exposed referents were identified using a P value < 1.06 × 10-7. Differential DNA methylation with epigenome-wide statistical significance was observed for 20 CpGs mapped to 11 genes, and 19 CpGs were correlated with gestational levels of PCBs or PCDF toxic equivalency (PCDF-TEQ) with the same direction of effect. Among the 11 genes, AHRR and CYP1A1 are involved in the aryl hydrocarbon receptor signaling pathway known to mediate dioxin toxicity. MYO1G, FRMD4A, ARL4C, OLFM1, and WWC3 were previously reported to be related to carcinogenesis. This is the first study examining genome-wide DNA methylation among people perinatally exposed to high concentrations of PCBs and PCDFs. We observed novel differential methylation of several genes, indicating that modifications of DNA methylation associated with perinatal PCB and PCDF exposure may persist in exposed offspring for more than 20 years. Furthermore, involvement of several carcinogesis-related genes suggested a potential in utero epigenetic mechanisms.

Evaluation of a Diagnostic Test of Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Urine KIM-1 in Contrast-Induced Nephropathy (CIN).

BACKGROUND The aim of this study was to assess changes in serum neutrophil gelatinase-associated lipocalin (NGAL) and urine KIM-1 after percutaneous coronary intervention (PCI). MATERIAL AND METHODS A total of 240 patients receiving coronary stent implantation were selected. All patients were divided into 2 groups: a CIN group (n=25) and a non-CIN group (n=215). The serum creatinine (SCr), NGAL, and urine KIM-1 levels of the patients in both groups were measured before and after surgery, and the sensitivity of serum NGAL and urine KIM-1 in diagnosing CIN in the early stage was assessed by the area under receiver operating characteristic (ROC) curve (ROC-AUC). RESULTS In the CIN group, the serum NGAL and urine KIM-1 levels started to rise at 6 h after surgery. The serum NGAL and urine KIM-1 levels in CIN group were significantly higher than those in the non-CIN group at 6, 12, 24, and 48 h after surgery. However, the SCr levels in the CIN group were not higher than those in the non-CIN group at 6 h after surgery. At 6, 12, and 24 h after PCI, the AUCs for serum NGAL and urine KIM-1 were increased compared with that for SCr, while the AUCs for serum NGAL and urine KIM-1 were decreased at 48 h after PCI compared with that for SCr. CONCLUSIONS Serum NGAL and urine KIM-1 levels in the patients after coronary stent implantation can reflect the changes in renal functions early, thus providing a certain basis for the early diagnosis of CIN.

[The Effects of Social Capital on Depressive Symptoms of Elderly Patients with Chronic Diseases in Urbanized Communities].

OBJECTIVE: To understand the effects of social capital on depressive symptoms of elderly patients with chronic diseases in urbanized communities, and to explore preventive measures to promote their mental health. METHODS: A multi-stage stratified cluster sampling method was used to extract 740 elderly patients with chronic diseases in the urbanized communities in Chengdu and Kunming. The questionnaire survey was conducted by using the center of depression rating scale (CES-D) and the self-made social capital scale. Multivariate unconditional logistic regression was used to analyze the impact of urbanized residents' social capital on depressive symptoms. RESULTS: The self-made social capital scale has good reliability and validity. The incidence of depressive symptoms in this study was 24.9%. The incidence of depressive symptoms in elderly females with chronic diseases was higher (P < 0.05); the residents with high "sense of social trust and security" had lower risk of incidence of depressive symptoms 〔odds ratio (OR)=0.489〕; the residents with higher "community belonging" had a lower risk of incidence of depressive symptoms (OR=0.570), and the residents with higher "social support" scores had a lower risk of incidence of depressive symptoms (OR=0.233). CONCLUSION: Targeted measures should be taken to intervene in the social capital factors affecting the depressive symptoms of elderly patients with chronic diseases in urbanized communities to improve their mental health.

Paraneoplastic Cerebellar Degeneration Associated with Pelvic Liposarcoma: A Rare Case Report.

Paraneoplastic cerebellar degeneration (PCD) is one of the most common paraneoplastic neurological syndromes characterized by the rapid development of severe cerebellar ataxia. In this report, a 23-year-old female with noticeable dizziness and gait instability was described. The enhanced CT scanning suggested the presence of a pelvic tumor. Then, PCD was established. Postoperative pathological result defined it as a liposarcoma (LS) with dedifferentiation. Interestingly, clinical symptoms disappeared after the surgical removal of the pelvic tumor. To our knowledge, this was the first case report with PCD due to LS.

Establishment and characterization of a kidney cell line from kelp grouper Epinephelus moara.

A novel cell line, Epinephelus moara kidney cell line (EMK), was established from kidneys of kelp grouper E. moara. Cells were cultured at 24 °C in Leibovitz's L-15 medium (L15) supplemented with antibiotics, basic fibroblast growth factor (bFGF), foetal bovine serum (FBS) and 2-mercaptoethanol (2-ME). EMK cells, fibroblastic in morphology, proliferated to 100% confluency in 3-4 days and were subcultured for over 50 passages. The cells could grow from 18 to 30 °C, with optimal growth at 24 °C. Chromosome analysis indicated that the modal chromosome number was 48 in the cells at passage 42. Green fluorescent signals could be observed in EMK cells when the cells were transfected with pEGFP-N3 plasmid. Moreover, a significant cytopathic effect (CPE) was observed in the cells after infection with Singapore grouper iridovirus (SGIV) or nervous necrosis virus (NNV), and viral replication was confirmed by quantitative real-time PCR (qPCR). These results suggested the potential of the EMK cell line for studies of transgene and pathogenesis of SGIV and NNV.

The Medicago truncatula R2R3-MYB transcription factor gene MtMYBS1 enhances salinity tolerance when constitutively expressed in Arabidopsis thaliana.

MYB-type proteins are known to participate in many stress responses, although their role in legumes is still less clear. Here, the isolation and characterization of MtMYBS1, an R2R3 MYB gene isolated from the model legume Medicago truncatula, is described. MtMYBS1 transcription was inducible by NaCl, polyethylene glycol or abscisic acid (ABA). When tested in yeast, its product was shown to have transactivational activity. The constitutive expression of MtMYBS1 in Arabidopsis thaliana seedlings mitigated the restriction on root growth imposed by either salinity or osmotic stress and raised their sensitivity to ABA. It also resulted in the plants being able to overcome several growth constraints and promoted activity in both the ABA-dependent and -independent stress-responsive pathways. In particular, it enhanced the transcription of P5CS, a gene which encodes a component of proline synthesis. MtMYBS1 may prove to be a useful gene for manipulating the salinity tolerance of legumes.

Clinicopathological significance of cancer stem cell marker CD44/SOX2 in esophageal squamous cell carcinoma (ESCC) patients and construction of a nomogram to predict overall survival.

Background: Esophageal squamous cell carcinoma (ESCC), a prevalent malignancy within the upper gastrointestinal system, is characterized by its unfavorable prognosis and the absence of specific indicators for outcome prediction and high-risk case identification. In our research, we examined the expression levels of cancer stem cells (CSCs), markers CD44/SOX2 in ESCC, scrutinized their association with clinicopathological parameters, and developed a predictive nomogram model. This model, which incorporates CD44/SOX2, aims to forecast the overall survival (OS) of patients afflicted with ESCC. Methods: Immunohistochemistry was utilized to detect the expression levels of CD44 and SOX2 in both cancerous and paracancerous tissues of 68 patients with ESCC. The correlation between CD44/SOX2 expression and clinicopathological parameters was subsequently analyzed. Factors impacting the prognosis of ESCC patients were assessed through univariate and multivariate Cox regression analyses. Leveraging the results of these multivariate regression analyses, a nomogram prognostic model was established to provide individualized predictions of ESCC patient survival outcomes. The predictive accuracy of the nomogram prognostic model was evaluated using the consistency index (C-index) and calibration curves. Results: The expression levels of CD44 were markedly elevated in the tumor tissues of ESCC patients. Similarly, SOX2 was significantly overexpressed in the tumor tissues of ESCC patients. The positive expression of SOX2 in ESCC demonstrated a strong correlation with both the pathological T-stage and the presence of carcinoembryonic antigen. CD44 and SOX2 co-positive expression was significantly associated with the pathological T-stage and tumor node metastasis (TNM) stage. Furthermore, ESCC patients exhibiting CD44-positive expression in their tumor tissue generally had a more adverse prognosis. The co-expression of CD44 and SOX2 resulted in a grimmer prognosis compared to patients with other combinations. Multivariate Cox regression analysis identified the co-expression of CD44 and SOX2, the pathological T-stage, and lymph node metastasis as independent prognostic indicators for ESCC patients. The three identified variables were subsequently incorporated into a nomogram for predicting OS. The C-index of the measurement model and the area under the curve of the subjects' work characteristics showed good individual prediction. This prognostic model stratified patients into low- and high-risk categories. Analysis revealed that the 5-year OS rate was significantly higher in the low-risk group compared to the high-risk group. Conclusions: Elevated CD44 levels, indicative of CSC presence, are intimately linked with the oncogenesis of ESCC and are strongly predictive of unfavorable patient outcomes. Concurrently, the SOX2 gene exhibits a heightened expression in ESCC, markedly accelerating tumor progression and fostering more extensive disease infiltration. The co-expression of CD44 and SOX2 correlates significantly with ESCC patient prognosis, serving as a reliable, independent prognostic marker. Our constructed nomogram, incorporating CD44/SOX2 expression, enhances the prediction of OS and facilitates risk stratification in ESCC patients.

Adiposity in Chinese people with type 1 diabetes.

Adiposity, synonymous with obesity, is prevalent among both children and adults with type 1 diabetes in China. Recent literature underscored the patho-physiological and socioeconomic factors associated with adiposity, and consistently highlighted its impact on cardiovascular, kidney, and metabolic diseases among Chinese individuals with type 1 diabetes. Addressing and managing adiposity in individuals with type 1 diabetes are complicated and entail comprehensive approaches including lifestyle modifications, cognitive-behavioral therapy, insulin dose titration, and other diabetes treatment medications. The condition calls for coordination among policymakers, researchers, clinicians, and patients.

Community factors to promote parents' quality of child-nurturing life.

OBJECTIVES: The purpose of this study was to clarify the role of community factors in parents' quality of child-nurturing life (QCNL). METHODS: We developed a questionnaire to evaluate the degree of QCNL and determine the structural factors related to QCNL as community factors related to parents' QCNL derived from focus group interviews and the Delphi technique. The questionnaire also included the battery of the self-rating depression scale and Tsumori-Inage Infant's Developmental Test. Using the questionnaire, we then conducted a quantitative survey of parents whose children attended nursery schools in Kumamoto Prefecture. Factor analysis, calculation of the mean score and/or ratio to each item, Pearson's correlation coefficient, t test, multiple regression analysis, and covariance structure analysis were performed. RESULTS: The questionnaire we developed consisted of seven items with 75 elements, involving ten elements as community factors. Subjects included 699 parents (mean age 33.6 ± 5.4 years) and 965 children (age range 0-6 years). Factor analysis revealed that community factors consisted of five factors, such as "lifestyle rooted in the ground," "balance of housekeeping and work," "community network," "amenity," and "regeneration of life". These factors may be dominant in a rural area. Finally, we developed a structural model with "community factors," QCNL, QOL, and "child growth" by covariance structural analysis. The analysis revealed that community factors had a positive relation to parents' QCNL (r = 0.81, p < 0.001) and that parental SDS score had a negative relation to parents' QCNL (r = -0.59, p < 0.001). The analysis did show that community factors were positively related to the sound growth of children. CONCLUSION: The covariance structure analysis revealed that community factors were associated with parents' QCNL, SDS, and "child growth."

Phosphorylation of AKT by lysyl oxidase-like 2 activates the PI3K/AKT signaling pathway to promote proliferation, invasion and metastasis in esophageal squamous carcinoma.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy of the gastrointestinal tract for which therapeutic options are scarce. This study screens for LOXL2, a key gene in ESCC, and explains the molecular mechanism by which it promotes the progression of ESCC. METHODS: Immunohistochemical staining was performed to detect the expression level of LOXL2 in ESCC tissues and paraneoplastic tissues. CCK-8 and Transwell assays were performed to assess the effects of LOXL2 knockdown and overexpression on the proliferation, apoptosis, migration and invasion ability of ESCC cells. High-throughput sequencing analysis screens for molecular mechanisms of action by which LOXL2 promotes ESCC progression. Western blotting and qRT-PCR were used to determine the expression levels of relevant markers. RESULTS: LOXL2 is positively expressed in ESCC and highly correlated with poor prognosis. Silencing LOXL2 significantly inhibited the proliferation, migration and invasive ability of ESCC cells, whereas overexpression showed the opposite phenotype. High-throughput sequencing suggested that LOXL2-associated differentially expressed genes were highly enriched in the PI3K/AKT signaling pathway. In vitro cellular assays confirmed that silencing LOXL2 significantly reduced PI3K, p-AKTThr308 and p-AKTSer473 gene and protein expression levels, while overexpression increased all three gene and protein levels, while AKT gene and protein expression levels were not significantly different. CONCLUSION: This study found that LOXL2 may regulate the PI3K/AKT signaling pathway and exert protumor effects on ESCC cells through phosphorylation of AKT. LOXL2 may be a key clinical warning biomarker or therapeutic target for ESCC.

Plant-on-chip: Core morphogenesis processes in the tiny plant Wolffia australiana.

A plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the minimalist known angiosperm to overcome this challenge and provide a model system for plant morphogenesis. We present a detailed morphological description of the monocot Wolffia australiana, as well as high-quality genome information. Further, we developed the plant-on-chip culture system and demonstrate the application of advanced technologies such as single-nucleus RNA-sequencing, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate how W. australiana can decipher the core regulatory mechanisms of plant morphogenesis.

Variations of trophic structure and niche space in fish community along a highly regulated subtropical large river.

The trophic interactions between consumers and resources play a vital role in the stability of communities. In river systems, fragmentation of natural habitats and environmental changes alters the energy basis and community composition, consequently leading to variations in the community's trophic structure and niche space. However, our understanding of how the trophic structure responds to environmental changes is still very limited. Here, based on stable isotope data, we explored and compared trophic positions (TPs), community-wide trophic metrics, and isotope niche space of fish communities in three reaches with different hydrogeomorphic conditions along a highly regulated subtropical river over three seasons. The community trophic structure and niche space showed notable spatiotemporal variations. Overall, the downstream reach had lower TPs, trophic diversity but higher trophic redundancy. The middle reach occupied a wider isotope niche space than other reaches, with the largest niche size during autumn. Furthermore, the niche overlap was relatively high in winter between reaches and in the downstream between seasons. The results implied a homogenization of feeding functional groups and energy flow pathways of species in the downstream community associated with the change of energy source and stability of hydrological conditions. The relationship between trophic structure and environmental factors suggested that the dam-induced alteration in hydrological-related aspects may drive the changes in the functional group composition, together with changes in energy basis, resulting in differences in the trophic structure of the community. The results of the present study deepen our understanding of how ecosystem functions respond to disturbance, thus contributing to improved ability to conserve river ecosystems.

Compare the Efficacy and Safety of Modified Combined Short and Long Axis Method versus Oblique Axis Method for Right Internal Jugular Vein Catheterization in Adult Patients (The MCSLOA Trial): Study Protocol of a Randomized Controlled Trial.

Background: Ultrasound-guided internal jugular vein (IJV) catheterization has become a standard procedure as it yields a higher success rate and fewer mechanical complications compared with an anatomical landmark technique. There are several common methods for ultrasound guidance IJV catheterization, such as short-axis out-of-plane, long-axis in-plane and oblique axis in-plane, but these technologies are still developing. It is important to further study the application of different ultrasound-guided IJV puncture techniques and find an effective and safe ultrasound-guided puncture technique. Methods: A China randomized, open-label, parallel, single center, positive-controlled, non-inferiority clinical trial will evaluate 190 adult patients undergoing elective surgery and need right jugular vein catheterization. Study participants randomized in a 1:1 ratio into control and experimental groups. The control group will take the oblique axis in-plane method for IJV catheterization. The experimental group will take the Modified combined short and long axis method. The primary endpoint of the trial is the rate of one-time successful guidewire insertion without posterior wall puncture (PWP). Secondary endpoints are the number of needle insertion attempts, the total success rate, the procedure time, and mechanical complications. Conclusion: This randomized controlled trial will evaluate the effectiveness and safety of Modified combined short and long axis method and oblique axis in-plane method for right IJV catheterization in adult patients.

Air-polluted environmental heavy metal exposure increase lung cancer incidence and mortality: A population-based longitudinal cohort study.

BACKGROUND: An increased risk of lung cancer has been observed due to exposure to certain environmental heavy metals. This study elucidated the role of air-polluted heavy metals in the development of lung cancer. METHODS: A longitudinal cohort study involving the general population was conducted to compare heavy metal content among lung cancer patients. The urine concentrations of heavy metals were measured. Questionnaire surveys were designed to collect exposure-related demographic and lifestyle data of the study subjects. RESULTS: Participants residing near the petrochemical industrial area with higher air Cd concentration had relatively higher urinary concentration of Cd. After adjusting for sociodemographic and behavioral factors, tobacco smoking and air pollution remained as potential sources of Cd exposure. An increased prevalence of lung cancer was observed in the highly polluted zone. The risk of lung cancer incidence increased 1.25-fold for each 1 µg/g-creatinine increase in urine Cd level. Patients with lung cancer had significantly higher urinary Cd concentrations. Lung cancer patients with higher urinary Cd level had significantly poor survival (urine Cd level ≥ 1.58 vs <1.58 µg/g-creatinine; survival, medium, 192.0 vs 342.5 days, p < 0.001). At the longitudinal follow-up, participants with higher urinary Cd level had a higher risk of lung cancer incidence (urine Cd level ≥ 1.58 vs <1.58 µg/g-creatinine: 3.91% v.s. 0.87%, hazard ratio: 4.65, p < 0.001). CONCLUSIONS: Accumulation of Cd could be a risk of lung cancer occurrence. High exposure to Cd may result in poor prognosis in lung cancer patients.

CXCR4 positive cells from Lewis lung carcinoma cell line have cancer metastatic stem cell characteristics.

There is increasing evidence that cancer stem cells contribute to the initiation and propagation of many tumor. Therefore, to find out and identify the metastatic tumor stem-like cells in Lewis lung cancer cell line (LLC), the expression of CXCR4 was measured in LLC by flow cytometry and observed by laser scanning confocal microscope (LSCM). After the CXCR4(+) LLC cell was isolated from LLC by magnetic cell sorting, its properties were evaluated by their tumorigenic and metastatic potentials. CXCR4(+) cells were counted for 0.18% of the total number of LLC, and immunofluorescent staining cells were identified by LSCM. CXCR4(+) LLC suspension cultured in a serum-free medium, cell spheres expressed a high level of Sca-1. The chemotherapy sensitivity to cisplatin of CXCR4(+) LLC was lower than that of CXCR4(-) LLC. The expression of ABCG2 and IGF1R mRNA in CXCR4(+) LLC was higher than that in CXCR4(-) LLC (P < 0.01). Most of CXCR4(+) LLC cells were close to vascular endothelial cells, aberrant vasculature around it was forming. The expression of VEGF and MMP9 mRNA in CXCR4(+) LLC was higher than that in CXCR4(-) LLC (P < 0.05), the microvessel density (MVD) of CXCR4(+) subsets growing were higher than that of CXCR4(-) subsets growing tumor tissue (P < 0.01). The tumor size, volume, and metastatic foci in the lungs of CXCR4(+) LLC was significantly higher than that in CXCR4(-) LLC (P < 0.001). Similarly, elevated expression of MMP9 and VEGF was also positively associated with CXCR4(+) LLC. Our results demonstrated that CXCR4(+) cells from Lewis lung carcinoma cell line exhibit cancer metastatic stem cell characteristics.

Comprehensive methylation profile of CSF cfDNA revealed pathogenesis and diagnostic markers for early-onset Parkinson's disease.

Background: Early-onset Parkinson's disease (EOPD) is one uncommon Parkinson's disease subtype with characteristic clinicopathological features. The full epigenomic profile of EOPD is largely unknown. Methods: We performed the first study to investigate the EOPD full methylation profile of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) from 26 EOPD patients and 10 control patients. Results: 2220 differentially methylated genes were identified in EOPD. Hypermethylation far outweighed hypomethylation in gene numbers. Clustering and enrichment analyses identified aberrant neuronal function and immune response. Weighted correlation network analysis demonstrated significant correlation between methylation signatures and clock drawing test (CDT), mini-mental state examination (MMSE), education, working status, alcohol drinking history and Hamilton anxiety scale (HAMA). Several key networking genes in EOPD aberrant methylation were also identified. Conclusions: The methylation profile and signatures of CSF cfDNA were revealed for the first time in EOPD. Aberrant methylation signatures were correlated with education, working status, alcohol drinking history, CDT, MMSE and HAMA.

Lay abstract Early-onset Parkinson's disease (EOPD), a progressive disease of the nervous system marked by tremor, muscular rigidity and slow and imprecise movement, is generally found in people under the age of 40 years. In this study, we performed methylation test on cerebrospinal fluid (CSF). The test showed that specific CSF methylation profiles could be used to help EOPD diagnosis. A subset of differentially methylated genes were also identified, which could also be used as markers for EOPD diagnosis. In future, we will validate the methylation test in blood and try to find blood-based diagnostic markers to facilitate the diagnosis of EOPD by a single blood draw.