The handgrip strength and risk of depressive symptoms: a meta-analysis of prospective cohort studies.

PURPOSE: Many studies have investigated the association between handgrip strength (HGS) and depressive symptoms, but the conclusion remain controversial. We performed a meta-analysis to evaluate the longitudinal association between HGS and risk of depressive symptoms. METHODS: PubMed, PSYCINFO and EMBASE databases were searched for eligible publications up to April 2020. Pooled relative risks (RRs) with 95% confidence intervals were calculated using random-effects model. Publication bias was estimated using Egger's test and the funnel plot. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of eligible studies. RESULTS: The present meta-analysis included 8 cohort studies with 30,727 participants. Overall, higher HGS was related to a decreased risk of depressive symptoms: the pooled risk ratio (RR) of 0.74 [95% confidence intervals (CI) 0.65-0.85] with a moderate heterogeneity (I2 = 60.5%, P = 0.013). HGS was significantly associated with a reduced risk of depressive symptoms in males (RR = 0.69; 95% CI 0.50-0.94), but not in females. CONCLUSIONS: Lower HGS was associated with an increased risk of depressive symptoms. Further studies are needed to confirm these findings and to investigate the sex differences.

Serum miR-638 Combined with Squamous Cell Carcinoma-Related Antigen as Potential Screening Biomarkers for Cervical Squamous Cell Carcinoma.

Aims: Cervical cancer is the second most common cause of cancer-related deaths in developing nations. Human papillomavirus prophylactic vaccines are not widely available, and there are shortages of gynecologists and cytologists in the already overburdened health care systems. The aim of this study was to identify circulating microRNAs (miRNAs) that could be used as feasible screening tests for cervical cancer in low-resource regions. Materials and Methods: Serum expression levels of five miRNAs were measured and validated by quantitative real-time polymerase chain reaction in cervical squamous cell carcinoma (CSCC) patients, cervical intraepithelial neoplasia patients, and healthy individuals. Squamous cell carcinoma-related antigen (SCC-Ag) was also measured in the serum. Results: Serum miR-638, miR-203a-3p, miR-1914-5p, and miR-521 levels were downregulated in the CSCC group (p < 0.05). Receiver operating characteristic (ROC) curve analysis indicated that the area under the ROC curve (AUC) values for miR-638 and miR-521 were 0.734 and 0.742, respectively, for discriminating CSCC patients from healthy controls. Furthermore, the combined use of miR-638 and SCC-Ag yielded the best screening performance and increased the AUC value, sensitivity, and specificity to 0.956, 94.87%, and 80.00%, respectively. Conclusion: This study suggested that miR-638 and miR-521 have independent screening value and that the combined measurement of miR-638 and SCC-Ag resulted in a better ability to discriminate patients with CSCC from healthy individuals.

Association between triclocarban and triclosan exposures and the risks of type 2 diabetes mellitus and impaired glucose tolerance in the National Health and Nutrition Examination Survey (NHANES 2013-2014).

BACKGROUND: There has been increasing interest in the concept that exposure to environmental chemicals may be contributing factors to epidemics of diabetes mellitus (DM). Triclocarban and triclosan (TCs) are synthetic antibacterial chemicals that are widely used in personal care products. Studies have shown that TCs are endocrine disruptors that alter metabolic conditions. However, it remains unclear whether exposure to TCs is a risk factor for impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). OBJECTIVE: We explored the hypothesis that TCs exposure is associated with an increased risk of IGT and T2DM. METHOD: To test our hypothesis, we analyzed the U.S. National Health and Nutrition Examination Survey (NHANES) cross-sectional data from 2013 to 2014. IGT and T2DM were diagnosed based on an oral glucose tolerance test (OGTT) and the WHO standards. The levels of urinary TCs were measured using an HPLC-MS/MS method that NHANES investigators developed. The association between urinary TCs status and IGT and T2DM was examined separately in men and women using multivariable logistic regression models adjusted for age, race, BMI, education, ratio of family income to poverty, smoking, exercise and hypertension. RESULTS: Nine hundred US participants (429 men and 471 women) were included in the analysis, of whom 242 (26.89%) were diagnosed with T2DM and 117 (13.00%) had IGT. Among women, there was a significant positive association between triclocarban, but not triclosan exposure and T2DM (OR: 1.79, 95% CI: 1.05, 2.05) after adjusting for potential confounding factors. Among men, no significant association between TCs exposure and IGT or T2DM was observed. CONCLUSIONS: Triclocarban exposure may increase the risk of T2DM in the women, although additional studies are needed to confirm the results of this study and to investigate the underlying mechanisms.

PM2.5 promotes replication of VSV by ubiquitination degradation of phospho-IRF3 in A549 cells.

Both PM2.5 and respiratory viruses are part of the atmospheric constituents. Respiratory viruses are often associated with PM2.5 exposure, but the mechanism of toxicity remains to be explored. The vitro models that adequately reproduce healthy cells or diseased cells exposing to PM2.5 and infecting VSV can provide a useful tool for studying innate immune mechanisms and investigating new therapeutic focus. In the environment of PM2.5, an infection model in which VSV infected A549 cells was established, that mimics the state in which the antiviral innate immune pathways are activated after the respiratory system is infected with RNA viruses. Subsequently, the model was exposed to PM2.5 for 24 h. PM2.5 could be ingested by A549 cells and synergize with VSV to inhibit cell viability and promote apoptosis. The expression of VSV-G were more abundant after VSV-infected A549 cells were exposed to PM2.5. Furthermore, PM2.5 inhibits VSV-induced IFN-ß expression in A549 cells. ISG15, CCL-5, and CXCL-10 had the same expression tendency with IFN-ß mRNA, consistently. Interestingly, when MG132 was applied, the expression of p-IRF-3 and IFN-ß proteins reduced by PM2.5 were refreshed. Conversely, the expression of VSV-G proteins were decreased. PM2.5 could degrade p-IRF-3 proteins by ubiquitination pathway to inhibit VSV-induced IFN-ß expression in A549 cells. Therefore, replication of the VSV viruses was promoted.

Association Study Between Methylation in the Promoter Regions of cGAS, MAVS, and TRAF3 Genes and the Risk of Cervical Precancerous Lesions and Cervical Cancer in a Southern Chinese Population.

A case-control study was used to explore the association between the methylation status in the promoter regions of the cGAS, MAVS, and TRAF3 genes and the diseases of cervical precancerous lesions (CPL) and cervical cancer (CC) in a Southern Chinese population, and to further explore their interaction effects with high-risk human papillomavirus (hrHPV) infection and environmental factors in these diseases. The study protocol was approved by the ethics committee of The First Affiliated Hospital of Jinan University, and this study was performed in 97 healthy controls, 75 patients with CPL and 33 patients with CC, while each participant has read and signed the informed consent forms before enrolment. The promoter methylation status genes were detected from the bisulfite-treated DNA by the bisulfite sequencing PCR (BSP) technique, which was carried out using MethPrimer. The cGAS, MAVS, and TRAF3 promoter methylation levels in CPL (CPL cGAS = 35.40%, CPL MAVS = 24.26%, and CPL TRAF3 = 96.76%) were significantly higher than those in the control (Control cGAS = 31.87%, Control MAVS = 21.16%, and Control TRAF3 = 96.26%, PcGAS < 0.001, PMAVS < 0.001, and PTRAF3 = 0.001); however, there was no significant differences between the CC and control. In the logistic regression model with adjusted covariates, compared with the individuals whose cGAS methylation levels were less than or equal to 31.87%, the women with the levels more than 31.87% increased the risk of CPL by 2.49 times (ORa = 2.49, 95% CI = 1.31-4.75, P a = 0.006). The women with MAVS methylation levels above 21.16% were 1.97 times more likely to have CPL than the those with the levels less than 21.16% (ORa = 1.97, 95% CI = 1.06-3.69, P a = 0.033). A synergistic interaction was found between hrHPV and gene promoter methylation levels of cGAS and MAVS in CPL; however, no potential interaction was observed in CC. The promoter methylation levels in cGAS, MAVS, and TRAF3 genes are higher in CPL than in control, indicating that hypermethylation might be an early event in the progression of cervical intraepithelial neoplasia (CIN). The interaction between the promoter methylation levels in cGAS and MAVS genes and hrHPV infection might play a role in the development of CPL.

Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population.

Objective: To evaluate the potential association between the genetic variants in miRNA processing genes (RAN, XPO5, DICER1, and TARBP2) and susceptibility to type 2 diabetes mellitus (T2DM) and its vascular complications, as well as to further investigate their interaction with environmental factors in type 2 diabetes. Methods: We conducted a case-control study in genotyping of five polymorphic loci, including RAN rs14035, XPO5 rs11077, DICER1 rs13078, DICER1 rs3742330, and TARBP2 rs784567, in miRNA processing genes to explore the risk factors for T2DM and diabetic vascular complications. Haplotype analyses, interactions of gene-gene and interactions of gene-environment were performed too. Results: We identified a 36% decreased risk of developing T2DM in individuals with the minor A allele in DICER1 rs13078 (OR: 0.64; 95%CI: 0.42-0.95; P: 0.026). The AA haplotype in DICER1 was also associated with a protective effect on T2DM compared with the AT haplotype (OR: 0.63; 95%CI: 0.42-0.94; P-value: 0.023). T2DM patients with the TT+TC genotype at RAN rs14035 had a 1.89-fold higher risk of developing macrovascular complications than patients with the CC genotype (OR: 1.89; 95%CI: 1.04-3.45; P-value: 0.037). We also identified two three-factor interaction models. One is a three-factor [DICER1 rs13078, body mass index (BMI), and triglyceride (TG)] interaction model for T2DM (OR: 5.93; 95%CI: 1.25-28.26; P = 0.025). Another three-factor [RAN rs14035, hypertension (HP), and duration of T2DM (DOD)] interaction model was found for macrovascular complications of T2DM (OR = 41.60, 95%CI = 11.75-147.35, P < 0.001). Conclusion: Our study provides new evidence that two single nucleotide polymorphisms (SNPs) of the miRNA processing genes, DICER1 and RAN, and their interactions with certain environmental factors might contribute to the risk of T2DM and its vascular complications in the southern Chinese population.

Toxoplasma gondii Cathepsin C1 inhibits NF-κB signalling through the positive regulation of the HIF-1α/EPO axis.

Toxoplasma gondii has evolved many successful strategies for immune evasion. However, the parasite-derived effectors involved in modulating NF-κB signalling pathway are largely unknown. T. gondii Cathepsin C1 (CPC1) is widely conserved among T. gondii strains and is important for T. gondii intracellular growth and proliferation. Our study showed that CPC1 protein could abrogate NF-κB activation after screening dense granule proteins. CPC1 suppressed NF-κB activation at or downstream of p65 and decreased the production of IL-1, IL-8, IL-6, IL-12, and TNF-α. Western blot analysis revealed that CPC1 inhibited phospho-p65 and CPC1 proteins primarily settled in cytoplasm. RNA sequencing analysis revealed that overexpression of CPC1 significantly upregulated erythropoietin (EPO), which can be induced by the hypoxia-inducible factor -1α (HIF-1α) during hypoxia. Furthermore, dual-luciferase reporter assays confirmed that CPC1 upregulated HIF-1α. Finally, both the knockdown of EPO and restriction of HIF-1α partially eliminated the suppression impact of CPC1 on the NF-κB signalling pathway. Our study identified a previously unrecognized role of CPC1 in the negative regulation of NF-κB activation through positive regulation of the HIF-1α/EPO axis. For the first time, CPC1 was shown to play an important role in immune evasion during T. gondii infection.

Silica nanoparticles as an enhancer in the IL-1ß-induced inflammation cycle of A549 cells.

Objective: The industrial production and combustion of coal can produce silica nanoparticles (nano-SiO2). It enters the human body mainly through the respiratory tract and exerts a toxic effect. However, whether nano-SiO2 can increase the IL-1ß-induced inflammatory expression in A549 cells has not been tested. Therefore, the synergistic toxicity of nano-SiO2 and IL-1ß to A549 was observed in our study. Materials and methods: We exposed A549 cells to nano-SiO2 (0, 100, 500, and 1000 µg/ml) for 12 and 24 h. The effect of nano-SiO2 on the viability of A549 cells was observed by the CCK-8 method. The A549 cells were exposed to nano-SiO2 (1 mg/mL) and cytokine IL-1ß (10 ng/mL) for 4 h, and we detected the expression of IL-1ß and IL-6 cytokines by real time quantitative polymerase chain (RT-qPCR) and enzyme linked immunosorbent assay (ELISA). The expression of ß-Actin, I-κB, phospho-ERK1/2 (P-ERK1/2), total-ERK1/2 (T-ERK1/2), phospho-JNK (P-JNK), total-JNK (T-JNK), phospho-P38 (P-P38), and total-P38 (T-P38) in A549 cells was detected by the Western Blot method. Results: The nano-SiO2 treatment resulted in a time-dependent decrease in the viability of A549 cells. The synergistic effect of nano-SiO2 and IL-1ß was observed on the new production of IL-1ß and IL-6 in A549 cells. The Western blot results showed that nano-SiO2 can increase the expression of IL-1ß and IL-6 by promoting the phosphorylation of ERK1/2 and elevating the phosphorylation of I-κB by IL-1ß. IL-1ß and IL-6 were induced by nano-SiO2, and the IL-1ß treatment with 20 µM of I-κBα phosphorylation inhibitor (PD98059) and 20 µM of ERK1/2 inhibitor (BAY11-7082) for 1 h was significantly lower than that of the control group in A549 cells. Discussion and conclusion: These results indicated that nano-SiO2 had a toxic effect on A549 cells, and this effect could increase IL-1ß on the A549 cell-induced inflammatory response. The results suggested that the release of IL-1ß and IL-6 in A549 was enhanced by the synergistic IL-1ß-induced phosphorylation of ERK1/2 and I-κB. This process is similar to a snowball, and it is possible that IL-1ß is continuously produced and repeatedly superimposed in A549 cells to produce an inflammatory effect; then, a vicious circle occurs, and an inflammatory storm is accelerated.

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population.

Persistent high-risk HPV infection is considered as a major cause of cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The RIG-I pathway in innate immunity plays an important role in antivirus response. Here, we hypothesized that altered function of mitochondrial antiviral signaling protein (MAVS) and mitochondrial TNF receptor-associated factor 3(TRAF3), key molecules downstream of the viral sensors RIG-I, may impair their ability of clearing HPV and thereby influence the risk for cervical precancerous lesions. To investigate the effects of MAVS and TRAF3 polymorphisms on susceptibility to cervical precancerous lesions, 8 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene-environment interactions were also calculated. We found that CA genotype of rs6052130 in MAVS gene were at 1.48 times higher risk of developing cervical precancerous lesion than individuals with CC genotype (CA vs. CC: ORadjusted = 1.48, 95% CI, 1.02-2.16). In addition, a significant synergetic interaction between high-risk HPV infection and rs6052130 was found on an additive scale. A significantly decreased risk of cervical precancerous lesions for the TC genotype of rs12435483 in the TRAF3 gene (ORadjusted = 0.67, 95% CI, 0.45-0.98) was also found. Moreover, MDR analysis identified a significant three-locus interaction model, involving high-risk HPV infection, TRAF3 rs12435483 and number of full-term pregnancies. Our results indicate that the MAVS rs6052130 and TRAF3 rs12435483 confer genetic susceptibility to cervical precancerous lesions. Moreover, MAVS rs6052130-mutant individuals have an increased vulnerability to high-risk HPV-induced cervical precancerous lesions.

Association Analysis of NLRP3 Inflammation-Related Gene Promotor Methylation as Well as Mediating Effects on T2DM and Vascular Complications in a Southern Han Chinese Population.

Objective: To explore the association between the methylation levels in the promoter regions of the NLRP3, AIM2, and ASC genes and T2DM and its vascular complications in a Southern Han Chinese population and further analyze their interaction and mediating effects with environmental factors in T2DM. Methods: A case-control study was used to determine the association between population characteristics, the methylation level in the promoter region of the NLRP3, AIM2, and ASC genes and T2DM and vascular complications. A mediating effect among genes-environment-T2DM and the interaction of gene-gene or gene-environment factors was explored. Results: In the logistic regression model with adjusted covariants, healthy people with lower total methylation levels in the AIM2 promoter region exhibited a 2.29-fold [OR: 2.29 (1.28~6.66), P = 0.011] increased risk of developing T2DM compared with higher-methylation individuals. T2DM patients without any vascular complications who had lower methylation levels (

Association Between SLC30A8 rs13266634 Polymorphism and Risk of T2DM and IGR in Chinese Population: A Systematic Review and Meta-Analysis.

Introduction: Published data regarding the association between solute carrier family 30, member 8 (SLC30A8) rs13266634 polymorphism and type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) risks in Chinese population are in-consistent. The purpose of this meta-analysis was to evaluate the association between SLC30A8 rs13266634 and T2DM/IGR in a Chinese population. Material and Methods: Three English (PubMed, Embase, and Web of Science) and three Chinese databases (Wanfang, CNKI, and CBMD database) were used for searching articles from January 2005 to January 2018. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated with the random-effect model. Trial sequential analysis was also utilized. Results: Twenty-eight case-control studies with 25,912 cases and 26,975 controls were included for SLC30A8 and T2DM. Pooled risk allele C frequency for rs13266634 was 60.6% (95%CI: 59.2-62.0%) in the T2DM group and 54.8% (95%CI: 53.2-56.4%) in the control group which had estimated OR of 1.23 (95%CI: 1.17-1.28). Individuals who carried major homozygous CC and heterozygous CT genotype were at 1.51 and 1.23 times higher risk of T2DM, respectively, than those carrying minor homozygous TT. The most appropriate genetic analysis model was the co-dominant model based on comparison of OR1, OR2 and OR3. Five articles that involved 4,627 cases and 6,166 controls were included for SLC30A8 and IGR. However, no association was found between SLC30A8 rs13266634 and IGR (C vs. T, OR = 1.13, 95%CI: 0.98-1.30, p = 0.082). TSA revealed that the pooled sample sizes of T2DM exceeded the estimated required information size but not the IGR. Conclusion: The present meta-analysis demonstrated that SLC30A8 rs13266634 was a potential risk factor for T2DM, and more studies should be performed to confirm the association between rs13266634 polymorphism and IGR.

Prevalence and genotype distribution of human papillomavirus among Hakka women in China.

BACKGROUND: Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. HPV genotypes are associated with varying degrees of pathogenicity. To better formulate strategies for cervical cancer prevention, we investigated the population-specific distribution of HPV genotypes, including those with high carcinogenicity. METHODS: From January to December 2012, a cervical cancer-screening program for HPV infection in Hakka women of Heyuan City Guangdong province was conducted. Of 736,000 women residents, 8,284 volunteers were recruited. The cytology specimens of 107 women were not adequate and excluded. Thus, 8,177 women submitted to polymerase chain reaction (PCR) sequencing of 16 HPV genotypes via MassARRAY spectrometry. RESULTS: Risk stratification based on genotypes indicated that the prevalence of overall, high-risk, and low-risk HPV infections was 12.27%, 14.20%, and 0.79%, respectively. Of the 1,003 women positively infected, 82.75% were infected with a single HPV type; 17.25% were infected with ≥2 types. Analysis revealed a U-shaped curve in HPV prevalence that correlated with age group, with peaks at ages 18-24 y (22.03%) and 60-65 y (25%). The most frequently detected HPV genotype was HPV-52 (26.81%), and then HPV-16 (17.54%), HPV-58 (14.25%), HPV-18 (10.16%), HPV-68 (8.27%), HPV-39 (5.68%), and HPV-51 (5.38%). CONCLUSIONS: HPV-52 is the most prevalent genotype infecting Hakka women. Therefore, vaccination against HPV-52 is imperative. The prevalence of HPV infection is highest in the younger (18-24 y) and older (60-65 y) age groups, indicating that screening for HPV in Hakka women should be performed early and maintained in the elderly.

[The expression of interleukin-25 in blood and nasal tissue of patients with chronic rhinosinusitis with nasal polyps].

OBJECTIVE: To explore the expression of interleukin-25 (IL-25) in chronic rhinosinusitis with nasal polyps (CRSwNP) and its potential significance in pathogenesis. METHOD: IL-25 expression in blood was detected by enzyme-linked immunosorbent assay (ELISA). IL-25 expression in tissue was detected by immunohistochemistry (LSAB method) from polyps (68 CRSwNP patients) and 55 inferior turbinate mucosa from patients with deviation of nasal septum served as control. Complete blood count and HE staining of blood and tissue eosinophil infiltration degree. RESULT: IL-25 expression in CRSwNP group were significantly higher than the control group, the difference was statistically significant (P < 0.01). IL-25 expression in local organizations was positively correlated with the number of eosinophil infiltration in CRSwNP group (r = 0.679, P < 0.01). CONCLUSION: The expression of IL-25 in CRSwNP patients mutually reinforcing and might increase eosinophil infiltration and play an important role in the development of CRSwNP.

[The specificity between "fei and dachang" in the lung injury of rats with ulcerative colitis].

OBJECTIVE: To observe the features of bronchopulmonary lesions in ulcerative colitis (UC) rats and the specificity with Fei and Dachang, thus providing reliance for the theory of "intestinal diseases involved Fei". METHODS: The UC rat model was duplicated by using rabbit intestine mucosa tissue allergenic model and TNBS-ethanol model. A normal rat group was set up as the control. The pulmonary functions [including inspiratory resistance (Ri), expiratory resistance (Re), forced vital capacity (FVC); FEV. 2/FVC, maximal voluntary ventilation (MVV), forced expiratory flow rate (FEF25% - 75%)], and indicators of liver and kidney functions [serum alanine aminotransferase (ALT), aspartate amino transferase (AST), blood urea nitrogen (BUN), and creatinine (Cr)] were detected in the two groups. The pathological changes of colon, lung, liver, and kidney were observed in the two groups. RESULTS: Rats in the model group in both acute and chronic stages had weight loss, mucus and loose stool. Partial rats had such symptoms as dyspnea, shortness of breath, and wheezing. Compared with the normal group, the MW, FVC, FEV0.2 and FEF25% -75% in the acute stage; Ri, Re, MVV, FVC, and FEF25% - 75% in the chronic stage all significantly decreased (P <0.05, P <0.01), and FEV0.2/FVC significantly increased in the model group (P <0.05). The pathological results showed interstitial pneumonia and pulmonary interstitial fibrosis in the model group. But the indicators of liver and kidney functions were all in the normal range. No obvious pathological change was seen in the renal and liver tissues in the two groups. CONCLUSIONS: UC could specifically induce bronchopulmonary lesions. Lung injury was one of UC's intestinal manifestations. The theory of "Fei and Dachang being interior-exteriorly correlated" was demonstrated from the theory of "intestinal diseases involved Fei".

[Change of coagulation functions and its significance in acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the changes and clinical significances of plasma D-dimer, factor X and tissue factor in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and analyze the in-depth changes of these indicators in AECOPD with co-current deep venous thrombosis (DVT). METHODS: A total of 56 AECOPD patients were divided into the DVT and non-DVT subgroups (n = 28 each). And 60 normal control subjects were recruited according to age and gender. For each subject, 2.7 ml whole blood was drawn and then the plasma levels of D-dimer, factor X and tissue factor were detected. The results were statistically analyzed with the software SPSS 13.0. And the analysis of variance was performed between the groups. RESULTS: There was no significant difference between the distribution of the AECOPD group and the control group by gender and age. Therefore two groups were comparable. And in the AECOPD group, there was no significant difference between the distribution of DVT and non-DVT subgroups by gender and age. Therefore these two subgroups were comparable as well. The value of D-dimer in the AECOPD patients was significantly higher than that in the normal control [(0.76 ± 0.30) vs (0.29 ± 0.11) mg/L, P < 0.01]; and in the AECOPD group, the value of D-dimer in the DVT subgroup was significantly higher than that in the non-DVT subgroup [(0.85 ± 0.29) vs (0.67 ± 0.28) mg/L, P < 0.05]. In the AECOPD group, the value of tissue factor was (238 ± 68) mg/L and the value of factor X (1181 ± 337) mg/L. While in the normal control group, the values were (124 ± 30) and (998 ± 260) mg/L respectively. As for tissue factor and factor X, there were significant differences between two groups (all P < 0.01). Yet in AECOPD patients, neither indicator had significant differences between the DVT and non-DVT subgroups (all P > 0.05). CONCLUSION: The blood of AECOPD patients is in a hypercoagulatory state. And an obvious rise in their plasma level of D-dimer suggests that it may be complicated with DVT.

Combination of sildenafil and simvastatin ameliorates monocrotaline-induced pulmonary hypertension in rats.

Sildenafil, a phosphodiesterase-5 inhibitor, and simvastatin, a cholesterol lowering drug, both have therapeutic effects on PAH; however, the combination of these drugs has not been tested in the treatment of PAH. The purpose of this study was to determine whether the combination of sildenafil and simvastatin is superior to each drug alone in the prevention of MCT-induced PAH. Phosphorylated Smad levels were decreased in lung tissue in MCT-injected rats, whereas ERK protein levels were increased. This indicates a possible role for an increase in mitogenic ERK activity in addition to decreased proapoptotic Smad signaling in the MCT model of PAH. Combination sildenafil and simvastatin treatment prevented the MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH), exerted an anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC). Our results indicate that combination therapy with sildenafil and simvastatin attenuated the development of pulmonary hypertension more than either treatment alone.

Decreased plasma soluble thrombomodulin levels as a risk factor for pulmonary thromboembolism.

OBJECTIVE: To observe the changes of the plasma soluble thrombomodulin (sTM) concentrations in patients with pulmonary thromboembolism (PTE) and assess the association between plasma sTM concentration and the risk of PTE. PATIENTS AND METHODS: We measured plasma concentrations of sTM, protein C (PC) and protein S (PS) and examined the association between those plasma markers and the risk of PTE in 72 selected PTE patients and 70 controls. RESULTS: Significant difference was identified in plasma sTM level between overall PTE patients and controls. Female PTE patients had statistically lower sTM concentrations than male patients. A positive linear correlation was found between plasma sTM concentration and age in female patients. Decreased plasma sTM concentration was associated with a continuously and progressively increased risk for PTE in women. The concentrations of plasma PC and PS did not differ between groups and no significant quantitative association was identified between the risk of PTE and the levels of plasma PC or PS. CONCLUSION: Decreased plasma sTM concentration is associated with an increased risk of PTE in women.

[Changes of blood coagulative and fibrinolytic system and function of pulmonary vascular endothelium after therapy in patients with acute pulmonary thromboembolism].

OBJECTIVE: To study the changes of blood coagulative and fibrinolytic system and the function of pulmonary vascular endothelium in the course of acute pulmonary thromboembolism (PTE) and after anticoagulant or thrombolytic treatment. METHODS: Twenty patients with acute non-massive PTE, 10 males and 10 females, aged (57 +/- 11) underwent anticoagulant treatment and 17 sex-, and age-matched acute massive PTE patients underwent thrombolytic treatment. The plasma level of D-dimer (D-D), thrombomodulin (TM), protein C (PC), protein S (PS), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and antithrombin-III (AT-III) activity were measured by ELISA before and after normal subjects severed as control group were included in the study. The plasma level of D-D, PS, PC, TM, t-PA and PAI-1 were measured by a method of ELISA before the treatment and six days after the anticoagulant treatment or 24 hours after the thrombolytic treatment. AT-III activity was measured by chromo-substrate method at the same time points. Forty sex- and age-matched healthy persons were used as controls. RESULTS: The plasma levels of D-D, t-PA, PS, and TM level of the anticoagulant group were all significantly higher and the AT-III activity of the 2 treatment groups was significantly lower than those of the controls before treatment (all P < 0.05); the plasma levels of D-D, t-PA, PAI-1, PS, and TM of the thrombolytic group were ala significantly higher and the AT-III activity was significantly lower than those of the control group before the treatment (all P < 0.05). After anticoagulant therapy, the plasma levels of D-D, t-PA, PS, and PC were significantly lower than those before treatment (all P < 0.05), however, the plasma levels of PAI-1, TM, and AT-III activity after treatment did not differ significantly from those before treatment. The plasma levels of D-D, t-PA, PS, PC, and TM after treatment of the thrombolytic group were all significantly lower than those before treatment (all P < 0.05), however, the plasma levels of PAI-1, TM, and AT-III activity after treatment did not differ significantly from those before treatment. CONCLUSION: Apparent imbalance in the blood coagulative and fibrinolytic system and pulmonary vascular endothelium damage occur in the patients with acute PTE. Combination tests of plasma D-D, AT-III, PS, PC, TM, t-PA and PAI-1 can give a more comprehensive explanation of the imbalance in the blood coagulative and fibrolytic system. Anticoagulant treatment and thrombolytic treatment play important roles in the regulation of the imbalance of coagulative and fibrinolytic system and protection of the function of pulmonary vascular endothelium of PTE patients.

[Changes of blood coagulative and fibrinolytic systems and functions of pulmonary vascular endothelium in patients with pulmonary thromboembolism].

OBJECTIVE: To explore the changes of blood coagulative and fibrinolytic systems and functions of pulmonary vascular endothelium in patients with pulmonary thromboembolism (PTE). METHODS: Twenty patients with acute massive PTE, 40 patients with acute non-massive PTE and 40 control subjects without PTE were included in the study. D-Dimer (D-D), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor1 (PAI-1), plasma protein S (Ps), plasma protein C (Pc), thrombomodulin (TM), anticardiolipin antibody (ACA) and homocysteine (Hcy) were measured by the method of ELISA. Antithrombin-III (AT-III) activity was measured by chromo-substrate method. RESULTS: The levels of D-D, t-PA, PAI-1, and TM were (1.46 +/- 0.62) mg/L, (11.4 +/- 6.9) microg/L, (88.2 +/- 27.5) microg/L, (6.8 +/- 1.1) microg/L respectively in patients with acute massive PTE and (0.92 +/- 0.27) mg/L, (6.6 +/- 1.5) microg/L, (60.1 +/- 26.1) microg/L, and (6.30 +/- 1.50) mg/L in patients with acute non-massive PTE. The levels of both PET groups were significantly higher than those of the control subjects [(0.38 +/- 0.10) mg/L, (4.7 +/- 1.4) microg/L, (35.7 +/- 9.2) microg/L, (3.0 +/- 0.5) microg/L and P < 0.05]. The levels of AT-III were (86.0 +/- 11.8)% in patients with acute massive PTE and (90.1 +/- 9.0)% in patients with acute non-massive PTE. The levels of AT-III in both groups were significantly lower than those of the control subjects, which were (102.6 +/- 9.2)% (P < 0.01 and P < 0.05 respectively). The levels of ACA-IgG, IgM and IgA in patients with acute massive PTE and non-massive PTE were also significantly higher than those in the control group (P < 0.05). CONCLUSION: Imbalance of blood coagulation and fibrolytic systems and pulmonary vascular endothelium damage occur in patients with PTE.