ABSTRACT
Objective: To investigate the expressions of Nod-like receptor protein 3 (NLRP3), cysteine-aspartic acid protease 1 (Caspase-1), and Gasdermin D (GSDMD) in nasopharyngeal carcinoma (NPC), and their relationships with the recurrence and metastasis of NPC. Methods: A retrospective study was conducted on 421 patients diagnosed with NPC between December 2014 and January 2020. The expressions of NLRP3, Caspase-1, and GSDMD in pathological specimens were examined with immunohistochemistry and multiplex immunofluorescence staining. Univariate and multivariate Cox regression analyses were applied to identify the factors influencing NPC recurrence and metastasis. In vitro experiments with NPC cell line HNE-2 were used to explore the functional mechanisms of NLRP3, Caspase-1, and GSDMD. Results: Multivariate Cox analysis revealed that tumor staging of â ¢-â £(HRrecurrence=2.74, 95%CIrecurrence: 1.61-4.65; HRmetastasis=1.90, 95%CImetastasis: 1.04-3.49) and pre-treatment plasma EBV-DNA levels≥1 500 copies/ml (HRrecurrence=1.91, 95%CIrecurrence: 1.13-3.23; HRmetastasis=2.07, 95%CImetastasis: 1.23-3.50)were independent risk factors for NPC recurrence and metastasis, while positive expression of NLRP3(HRrecurrence=0.17, 95%CIrecurrence: 0.08-0.35; HRmetastasis=0.30, 95%CImetastasis: 0.15-0.59), Caspase-1(HRrecurrence=0.32, 95%CIrecurrence: 0.18-0.59; HRmetastasis=0.43, 95%CImetastasis: 0.25-0.76), and GSDMD(HRrecurrence=0.48, 95%CIrecurrence: 0.25-0.91; HRmetastasis=0.96, 95%CImetastasis: 0.53-1.74) served as independent protective factors. Age (HR=1.02, 95%CI: 1.01-1.04) and intensity-modulated radiotherapy (HR=0.51, 95%CI: 0.30-0.88) were independent factors for NPC recurrence, whereas chemotherapy (HR=0.50, 95%CI: 0.29-0.88) acted as an independent protective factor for NPC metastasis (all P<0.05). NPC patients with positive expressions of the three proteins had higher locoregional recurrence-free survival, distant metastasis-free survival, and overall survival compared to those with negative expressions (all P<0.05). In vitro experiments revealed that the overexpression of NLRP3 activated the NLRP3/Caspase-1/GSDMD signaling pathway, as evidenced by Western Blot analysis. Enzyme-linked immunosorbent assay and scanning electron microscopy demonstrated that overexpression of NLRP3 promoted pyroptosis in HNE-2 cells. Cellular functional assays further confirmed that overexpression of NLRP3 significantly inhibited the proliferation, invasion, and migration of HNE-2 cells. Conclusion: Positive expressions of NLRP3, Caspase-1, and GSDMD serves as independent protective factors for recurrence and metastasis of NPC, potentially by promoting cell pyroptosis and thus inhibiting NPC cell proliferation, invasion, and migration.
Subject(s)
NLR Family, Pyrin Domain-Containing 3 Protein , Nasopharyngeal Neoplasms , Humans , Caspase 1 , Gasdermins , Nasopharyngeal Carcinoma , Phosphate-Binding Proteins , Retrospective StudiesABSTRACT
It has been known for decades that the observed number of baryons in the local Universe falls about 30-40 per cent short1,2 of the total number of baryons predicted 3 by Big Bang nucleosynthesis, as inferred4,5 from density fluctuations of the cosmic microwave background and seen during the first 2-3 billion years of the Universe in the so-called 'Lyman α forest'6,7 (a dense series of intervening H I Lyman α absorption lines in the optical spectra of background quasars). A theoretical solution to this paradox locates the missing baryons in the hot and tenuous filamentary gas between galaxies, known as the warm-hot intergalactic medium. However, it is difficult to detect them there because the largest by far constituent of this gas-hydrogen-is mostly ionized and therefore almost invisible in far-ultraviolet spectra with typical signal-to-noise ratios8,9. Indeed, despite large observational efforts, only a few marginal claims of detection have been made so far2,10. Here we report observations of two absorbers of highly ionized oxygen (O VII) in the high-signal-to-noise-ratio X-ray spectrum of a quasar at a redshift higher than 0.4. These absorbers show no variability over a two-year timescale and have no associated cold absorption, making the assumption that they originate from the quasar's intrinsic outflow or the host galaxy's interstellar medium implausible. The O VII systems lie in regions characterized by large (four times larger than average 11 ) galaxy overdensities and their number (down to the sensitivity threshold of our data) agrees well with numerical simulation predictions for the long-sought warm-hot intergalactic medium. We conclude that the missing baryons have been found.
ABSTRACT
OBJECTIVE: To investigate the effects of HOXD cluster antisense RNA 1 (HOXD-AS1) in cervical cancer and its underlying mechanism. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of HOXD-AS1 in human cervical cancer tissues. x2-test was used for analyzing the association of HOXD-AS1 expression and clinical parameters. Cell viability, colony formation capacity, and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) in treated HeLa and CaSki cells were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, colony formation assay, and Western blot analysis, respectively. RESULTS: The results indicated that HOXD-AS1 was upregulated in cervical cancer cells significantly. Meanwhile, HOXD-AS1 expression was involved in tumor-node-metastasis stages, lymphovascular invasion, lymph node metastasis, as well as recurrence. HOXD-AS1 knockdown remarkably suppressed cervical cancer cell proliferation, colony formation capacity, and the Ras/ERK signaling pathway in vitro. Furthermore, xenograft assays confirmed the results in vivo. CONCLUSIONS: Our data elucidate that silencing HOXD-AS1 remarkably suppresses cell growth by inactivating the Ras/ERK pathway in cervical cancer, providing a more detailed understanding of cervical cancer pathogenesis and providing a possible theoretical foundation for long non-coding RNA for the diagnosis and therapy for cervical cancer.
Subject(s)
Cell Proliferation , Extracellular Signal-Regulated MAP Kinases/metabolism , RNA, Long Noncoding/metabolism , Signal Transduction , Uterine Cervical Neoplasms/pathology , ras Proteins/metabolism , Animals , Cell Line, Tumor , Female , HeLa Cells , Humans , Lymphatic Metastasis , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neoplasm Recurrence, Local , RNA Interference , RNA, Long Noncoding/antagonists & inhibitors , RNA, Long Noncoding/genetics , RNA, Small Interfering/metabolism , Up-Regulation , Uterine Cervical Neoplasms/metabolismABSTRACT
The phylogenetic and epidemic relationships of 104 clinical isolates of Clostridium difficile from three hospitals of different geographical and population sources in China were investigated by multilocus sequence typing. Twenty-two sequence types (STs) were identified, four of which, ST117, ST118, ST119 and ST129, were novel. No geographically specific and host population-specific phylogenetic lineages were found and there was no correlation between geographical origin or host population and strain genotype. ST37 was the dominant type in our survey but the four novel STs underline the high genetic diversity and unique polymorphisms in C. difficile from China.
Subject(s)
Clostridioides difficile/classification , Clostridioides difficile/isolation & purification , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Multilocus Sequence Typing , Adolescent , Adult , Aged , Aged, 80 and over , Child, Preschool , China/epidemiology , Clostridioides difficile/genetics , Cluster Analysis , Female , Humans , Infant , Male , Middle Aged , Molecular Epidemiology , Phylogeny , Young AdultABSTRACT
The formation rate of luminous galaxies seems to be roughly constant from z approximately 2 to approximately 4 from the recent observations of Lyman break galaxies (LBGs). The abundance of luminous quasars, on the other hand, appears to drop off by a factor of more than 20 from z approximately 2 to z approximately 5. The difference in evolution between the two classes of objects in the overlapping, observed redshift range (z=2-4) can be explained naturally if we assume that quasar activity is triggered by mergers of luminous LBGs and one quasar lifetime is approximately 107-108 yr. If this merger scenario holds at higher redshift, for the evolutions of these two classes of objects to be consistent at z>4, the formation rate of luminous LBGs is expected to drop off at least as rapidly as exp-&parl0;z-4&parr0;6&solm0;5 at z>4.
ABSTRACT
The development and the tendency of the problems of developing flow in the vessel are reviewed in this paper. It is pointed out that the problems of developing flow of viscoelastic blood vessel are front subjects, and that consideration shouldbe be give to three aspects, namely the blood flow, the blood vessel's wall motion and the coupling between the blood and the wall.
Subject(s)
Blood Flow Velocity/physiology , Blood Vessels/physiology , Elasticity , Models, CardiovascularABSTRACT
BACKGROUND: Previous studies of western populations have shown an inverse association between lung function and blood pressure. METHODS: As part of a People's Republic of China-United States cardiopulmonary epidemiology study, we investigated the cross-sectional relationship between lung function and blood pressure in 6757 Chinese men and women, aged 35-54, from Beijing and Guangzhou, China. We also evaluated the longitudinal association between lung function and incident hypertension among 4818 initially normotensive subjects followed up between 2 and 4 years later. RESULTS: In our cross-sectional analyses of baseline data, lung function varied inversely with baseline systolic (SBP) and diastolic blood pressure (DBP) in all women and in Beijing men. This association held for absolute and height-standardized forced vital capacity (FVC) and one-second forced expiratory volume (FEV1) (correlations: 0.10, -0.18, P < 0.0001), but was weaker after adjustment for age (correlations: -0.02, -0.11). The longitudinal follow-up showed that lower initial lung function levels were associated with a higher incidence of hypertension (SBP > or = 140 mmHg or DBP > or = 90 mmHg or currently using antihypertensive medications), but only among women in Guangzhou. Relative risks for hypertension incidence for those in the two lowest quintiles for FEV1 and FVC, compared to those in the two highest quintiles, ranged from 1.9 to 2.3 for Guangzhou women and from 0.9 to 1.4 for all other gender-city subgroups. Logistic regression analyses adjusting for age, baseline SBP, body mass index, smoking, education, and urban versus rural setting generally confirmed these patterns. CONCLUSIONS: These results suggest a statistically significant, though weak, inverse relationship between lung function and blood pressure in Chinese men and women. This association is largely attributable to age and is present prospectively only in women.
Subject(s)
Blood Pressure Determination , Hypertension/epidemiology , Respiratory Function Tests , Adult , Age Distribution , China/epidemiology , Cohort Studies , Cross-Sectional Studies , Female , Humans , Hypertension/diagnosis , Incidence , Logistic Models , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Risk Factors , Sex DistributionABSTRACT
OBJECTIVE: To assess comparative changes in systolic and diastolic blood pressure and incidence of high blood pressure over 4 years, and factors related to these changes, in northern and southern, urban and rural adults in the People's Republic of China. SETTING: This is a prospective study of populations surveyed by standardized methods in 1983-1984 and 1987-1988 in north China, Beijing area steel mill workers and farmers, and south China, Guangzhou area shipyard workers and farmers. SUBJECTS: The subjects were 8805 men and women aged 35-54 years at baseline (1983-1984), of whom 7338 were non-hypertensive (systolic blood pressure < 140, diastolic blood pressure < 90 mmHg, not being administered antihypertensive drugs). MAIN OUTCOME MEASURES: The main outcome measures were 4-year changes in systolic and diastolic blood pressures and the 4-year incidence of high blood pressure in persons not hypertensive at baseline. RESULTS: At baseline, the average systolic and diastolic blood pressures were higher for Beijing than for Guangzhou cohorts. At resurvey the average systolic blood pressure had increased for seven of eight sex-city-setting cohorts (all but Guangzhou urban men). The Beijing urban cohorts had the greatest increases (men 6.2 mmHg, women 4.9 mmHg, slopes of 1.6 and 1.2 mmHg/year). The incidence of high blood pressure was higher for Beijing than for Guangzhou cohorts in all four comparisons (men and women, urban and rural). Beijing men, urban and rural, had the highest incidence rates (about 21%). In multiple logistic analyses by sex, variables significantly related to 4-year high blood pressure incidence were city, baseline systolic blood pressure and body mass index, change in weight, and, for men, baseline alcohol use and heart rate. CONCLUSION: Modifiable lifestyle traits, previously shown to be related to blood pressure and high blood pressure in cross-sectional studies, also relate to the incidence of hypertension.
Subject(s)
Blood Pressure , Hypertension/epidemiology , Adult , China/epidemiology , Cohort Studies , Diastole , Female , Follow-Up Studies , Humans , Hypertension/physiopathology , Incidence , Male , Middle Aged , Prospective Studies , SystoleABSTRACT
Gravitational lensing provides a strict test of cosmogonic models because it is directly sensitive to mass inhomogeneities. Detailed numerical propagation of light rays through a universe that has a distribution of inhomogeneities derived from the standard CDM (cold dark matter) scenario, with the aid of massive, fully nonlinear computer simulations, was used to test the model. It predicts that more widely split quasar images should have been seen than were actually found. These and other inconsistencies rule out the Cosmic Background Explorer (COBE)-normalized CDM model with density parameter Omega = 1 and the Hubble constant (H(o)) = 50 kilometers second(-1) megaparsec(-1); but variants of this model might be constructed, which could pass the stringent tests provided by strong gravitational lensing.
ABSTRACT
The associations of body mass index and abdominal adiposity, represented by an elevated waist/hip circumference ratio, with cardiovascular risk factors were examined in men and women, aged 28-69 years, from urban and rural areas of Guangzhou, China. Mean body mass index ranged from 20.1 to 21.9 kg/m2 across the four sex- and area-groups. Mean waist/hip ratio was 0.84 in men and 0.80 in women. After accounting for age and body mass index, waist/hip ratio was associated negatively (p < 0.05) with fasting serum HDL cholesterol (both sexes), and positively with serum triglycerides (both sexes), total and LDL cholesterol (men only), uric acid (both sexes), glucose (women only), and mean systolic blood pressure (women only). Body mass index was associated in a similar direction with most of these risk factors. These data confirm that abdominal adiposity is independently associated with cardiovascular disease risk factors, even in a lean Asian population.
Subject(s)
Adipose Tissue/anatomy & histology , Body Constitution , Body Mass Index , Cardiovascular Diseases/epidemiology , Abdomen , Adult , Aged , Alcohol Drinking , Anthropometry , Blood Glucose/analysis , Blood Pressure , China/epidemiology , Cholesterol, HDL , Cholesterol, LDL/blood , Cohort Studies , Female , Humans , Linear Models , Male , Middle Aged , Risk Factors , Rural Population , Triglycerides/blood , Urban Population , Uric Acid/bloodABSTRACT
As part of the PRC-USA collaborative research project on the epidemiology of cardiovascular disease, baseline surveys were conducted in four random urban and rural samples in Guangzhou, Guangdong Province in southern China on 334 men and women aged 35-54 in the fall of 1983-84 with the aim of studying the correlation between dietary intakes and serum lipids. Methods standardized by the US Centers for Disease Control were used for measuring different parameters, and quality control was emphasized to assure comparability between workers and farmers. Three 24-hour recalls were collected from each participant in each survey. Mean values of daily intakes of nutrients per capita for the four groups were as follows: 59-69% kcal carbohydrate; 10-12% kcal protein; 22-26% kcal fat. Dietary total fat, saturated fatty acid (SFA), polyunsaturated fatty acid (PUFA) and cholesterol were higher in the urban than the rural areas. Mean levels of serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were 4.6 mmol/l, 1.1 mmol/l, 1.3 mmol/l and 2.8 mmol/l respectively. The TC, TG and LDL-C and HDL-C were significantly higher in the urban than the rural areas. Analyses of correlation showed that the Keys 'dietary lipid score' was positively associated with TC, LDL-C and HDL-C; specifically, dietary cholesterol was positively associated with serum TC. Saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) were positively correlated with HDL-C. It seems that the traditional dietary pattern of Guangzhou favours serum lipids being at an optimal level.
ABSTRACT
In 1983 and 1984, surveys were conducted in four Chinese population samples, urban and rural for both Beijing and Guangzhou, as part of PRC-USA collaborative research in cardiovascular and cardiopulmonary epidemiology. Serum total cholesterol (TC), HDL-cholesterol (HDL-C), and triglycerides (TG) were measured in 4280 men and 4695 women aged 35-54 years, in laboratories standardized by the US Centers for Disease Control. Age-adjusted mean serum TC was higher in urban than rural samples and generally higher in Beijing than Guangzhou, ranging from 155 mg/dL for Guangzhou rural women to 187 mg/dl for Guangzhou urban women. Group mean values of HDL-C varied from 48 to 59 mg/dl, higher in Beijing than Guangzhou, and higher in women than men. TC/HDL-C ratio ranged from 3.05 to 3.82. Serum TG values were higher for Beijing than Guangzhou; the lowest group mean values of 78 mg/dl and 75 mg/dl were in rural Guangzhou men and women. Mean body mass index (BMI) was uniformly low, ranging from 20 kg/m2 for rural Guangzhou to 24 kg/m2 for urban Beijing. Multiple regression analyses showed that BMI was positively and independently related to serum TC, LDL-C, TG, and TC/HDL-C, and inversely related to HDL-C. Smoking was positively related in both sexes to TG and TC/HDL-C, and inversely related to HDL-C. Smoking was also positively related to TC and LDL-C in men. In men, alcohol was positively related to TC and HDL-C, and was inversely related to TG and TC/HDL-C. Heavy manual work was inversely related to TC, LDL-C, and TC/HDL-C in men, but not related to lipids in women. Thus, for these Chinese population samples, despite their lower serum TC and BMI, the correlates of serum lipids are similar to those in western populations. These variables accounted for only part of the observed urban-rural and north-south differences in serum lipids among these Chinese population samples. The significance of the relatively low serum TC and TG and high HDL-C in relation to low cardiovascular disease in Chinese populations is the object of further investigation in follow-up studies.
Subject(s)
Lipids/blood , Rural Population , Urban Population , Adult , Alcohol Drinking/epidemiology , China/epidemiology , Cholesterol/blood , Coronary Disease/epidemiology , Female , Humans , Male , Middle Aged , Regression Analysis , Smoking/epidemiology , Triglycerides/blood , United StatesABSTRACT
As part of the International Cooperative Cardiovascular Diseases and Alimentary Comparison (CAR-DIAC) Study surveys to determine the relationship of dietary factors to blood pressure were carried out in 1985 (pilot study) and 1989 (core study). Thirteen men and 16 women, and 102 men and 115 women aged 50-54 in the rural population of Panyu county in Guangzhou were randomly selected for the pilot and core studies, respectively. Blood pressure was measured by an automatic system and 24-h urine collection by aliquot cups. All urinary specimens were analyzed in the WHO Collaborating Center (Izumo, Japan). Seven hypertensive cases and 17 borderline cases of hypertension were found in 1989 but none in 1985. Mean systolic blood pressure (SBP) and diastolic blood pressures (DBP) were increased, and the intake of dietary sodium (Na), sodium chloride (NaCl), and the ratio of sodium to potassium (Na/K) were increased markedly. The intake of magnesium (Mg) was decreased in 1989. Correlation analyses showed that body mass index was positively related to SBP and DBP (p less than 0.05), Na and NaCl were positively related only to DBP (p less than 0.05), and Mg was inversely related to SBP but with no statistical significance. These results indicate that trends of rise of prevalence rate of hypertension and mean values of SBP and DBP in association with increased dietary Na and decreased Mg intake may be due to rapid changes in dietary habits, changes in lifestyle, and the differing socioeconomic status in the area and may highlight the importance of dietary factors in the prevention of hypertension.
Subject(s)
Blood Pressure , Diet/trends , Hypertension/epidemiology , China/epidemiology , Female , Humans , Hypertension/physiopathology , Magnesium/urine , Male , Middle Aged , Pilot Projects , Sodium/urineABSTRACT
Mortality data obtained from the Health Statistics Office of the Ministry of Health, People's Republic of China (PRC), were compared to data for other countries taken from the World Health Statistics Annual. The crude death rate for coronary heart disease (CHD) in China in 1984 is estimated to be about one-tenth of that for North America and Australia. However, a high stroke to CHD ratio of about 5.0 was observed in China. The age-standardized CHD mortality rates were significantly higher for Beijing in north China than for Shanghai and Guangzhou in the south, and for urban than rural populations in all years from 1976 to 1986. Data on hospital admissions and autopsy material provide evidence for an increase in CHD incidence and prevalence in the last three to four decades. A low mean serum total cholesterol, related to a low habitual dietary intake of fat and cholesterol, is considered to be the main cause underlying low CHD mortality rates in China.
Subject(s)
Coronary Disease/mortality , Adult , Aged , China/epidemiology , Cholesterol/blood , Coronary Disease/epidemiology , Diet , Female , Hospitalization , Humans , Hypertension/epidemiology , Male , Middle Aged , Rural Population , Smoking/epidemiology , Urban PopulationABSTRACT
The problem of oscillatory flow in a circular pipe was analyzed by Atabek and associates more than two decades ago. Their formulas for velocity and pressure distributions in developing pipe flows under oscillatory conditions have been often cited. However, the application of these formulas for flow field computations requires a rather complex procedure involving plotting of a set of curves and predetermination of the phase angles. This paper presents a method using the imaginary argument of the Bessel function to solve the Navier-Stokes equations. A different set of solution formulas are obtained. A comparison of the formulas obtained in this paper with those of Atabek shows that the former is considerably simpler and more convenient to use in flow computations. Numerical results computed using this paper's formulas are consistent with Atabek's and with the experimental measurements.