[Analysis on epidemiological characteristics of pneumoconiosis in Qinghai Province from 2011 to 2020].

Objective: To analyze the epidemiological characteristics of pneumoconiosis in Qinghai Province from 2011 to 2020, and to provide a basis for the formulation of prevention and control strategy. Methods: In April 2021 , the cases of pneumoconiosis were monitored by the Occupational Disease and Health Hazard Factors Monitoring Information System in Qinghai Province from 2011 to 2020. The distribution of pneumoconiosis, the composition of diseases and the working years exposed to dust were analyzed. Results: All 1026 cases of pneumoconiosis were newly diagnosed in Qinghai Province from 2011 to 2020, silicosis and coal worker pneumoconiosis were the main diseases (78.36% ,804/1026). Stage Ⅰ pneumoconiosis were 484 (47.17%,484/1026) cases. 359 (34.99%,359/1026) cases, 315 (30.70%,315/1026) cases and 252 (24.56%, 252/1026) cases had been diagnosed respectively in Xining City, Haidong City and Haixi Prefecture; 628 (61.21%,628/1026) cases and 418 (40.74%, 418/1026) cases engaged in mining industry and large-sized enterprise, respectively. The working years exposed to dust in silicosis cases were shorter than that in coal worker pneumoconiosis and other pneumoconiosis (P <0.05). Conclusion: The pneumoconiosis area and industry focus in Qinghai Province is obvious. The supervision and adninistration of small and micro scale employers should be strengthened to protect the health rights and interests of workers, especially for the key area and industry.

[Relationship between occupational stress and working ability of workers in a petroleum processing enterprise in high altitude area].

Objective: To investigate the relationship between occupational stress and working ability of workers in a petroleum processing enterprise in a high altitude area. Methods: A total of 728 workers in a petroleum processing enterprise at an altitude of 2850 m were subjected to a survey using Occupational Stress Inventory (OSI) , Work Ability Index (WAI) Scale, Occupational Role Questionnaire (ORQ) , Personal Strain Questionnaire (PSQ) , and Personal Resource Questionnaire (PRQ) from May 2014 to August 2016. Results: Of the 728 workers, 55 (7.6%) had a poor working ability, moderate in 262 (35.9%) , and good in 411 (56.5%). There were significant differences in WAI between the workers with different types of work, sexes, ages, and working years (P<0.05). There was a significant difference in WAI between different occupational stress groups (P<0.05). WAI was negatively correlated with ORQ score and PSQ score (r(s)=-0.387, P<0.05; r(s)=-0.467, P<0.05) and positively correlated with PRQ score (r(s)=0.343, P<0.05). The multiple linear regression analysis showed that high ORQ score and PSQ score were the inhibitory factors for high WAI (B=-0.058; B=-0.082) and high PRQ score was a contributing factor for high WAI (B=0.029) . Conclusion: Occupational stress is an influencing factor for the working ability of workers in the petroleum processing enterprise in the high altitude area. Hypoxia in high altitude area may further reduce the working ability. In order to reduce occupational stress and improve work ability, it should be considered to strengthen skills training, improve the working environment, and pay attention to mental health.

Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity.

Enterovirus 71 (EV71) infection commonly strike children under the age of 3 years, with an occasionally unfavorable outcome in children. This study was designed to explore the relationship between age and the severity of complications, which may associate with antibody-dependent enhancement (ADE) in EV71. All EV71-infected patients during the outbreak of 2008 were recruited. In total, 134 patients were enrolled and categorized into two age groups, 0-12 months (n = 18) and >12 months (n = 116). Pulmonary edema/hemorrhage more commonly occur in patients younger than 12 months. No difference in the occurrence of herpangina/hand-foot-and-mouth disease (HFMD), uncomplicated brainstem encephalitis (BE), or autonomic nervous system (ANS) dysregulation was noted between the two age groups. Patients with pulmonary edema/hemorrhage (11.9 ± 14.7 months) were younger than patients with herpangina/HFMD (35.8 ± 26.4 months) or ANS dysregulation (33.9 ± 20.9 months). Our findings are in agreement with the data regarding the outbreak in Taiwan, in which a decrease in age corresponded to an increase in disease severity with regard to central nervous system complications. A reduction of maternal antibodies to the subneutralizing level within 1 year of age may be associated with the ADE of the infection. This study could provide possible clinical significance with regard to ADE phenomena in young infants infected by EV71.

Regulation of immune responses by I-J gene products. VI. Recognition of I-E molecules by I-J-bearing suppressor factors.

Poly(Glu50Tyr50) (GT) is not immunogenic in most inbred mouse strains. GT injection produces an I-J--bearing, GT-specific T-cell--derived suppressor factor (GT-TsF1) in H-2b,d,k haplotype mice. GT-TsF1 generates second-order suppressor T cells (Ts2) in H-2a,d,k haplotype mice. Here, we show that in order for GT-TsF1 to act, the recipient strain must express I-E molecules. This suggests that T cells are not the primary target of GT-TsF1. GT-TsF1 can be presented by Ia+ A20-2J B lymphoma cells. GT-TsF1 presentation is blocked by anti-I-E, but not by anti--I-A, mAb, whereas GAT presentation is blocked by anti-I-A, but not by anti--I-E, mAbs. These data suggest that I-J recognizes (or is recognized by) I-E. The existence and role of I-J molecules in immune regulation are discussed in light of these data.

Regulation of immune responses by I-J gene products. II. Presence of Both I-Jb and I-Jk suppressor factors in (nonsuppressor x nonsuppressor) F1 mice.

Antigen-specific suppression to poly(Glu50-Tyr50) (GT) is under the control of two complementary immune suppressor (Is) genes located in the major histocompatibility (H-2) complex of the mouse. Suppressor strains of mice produce both suppressor T (Ts) cells and Ts-derived suppressor factors (TsF) that bear antigenic determinants of the I-J subregion of the H-2 complex. Nonsuppressor strains of mice, on the other hand, are not suppressed by GT preimmunization. These nonsuppressor mice, however, can be classified according to those that lack the ability to make GT-specific T cell-derived suppressor factor (GT-TsF) after GT injection (i.e., H-2a, I-Jk mice) and those that lack the ability to be suppressed by the appropriate GT-TsF (i.e., H-2b,g2, I-Jb mice). In the present study, we demonstrate that (H-2a x H-2b,g2)F1 hybrid mice produce distinct GT-specific suppressor factors of both parental I-J haplotypes. Moreover, only the I-Jb-bearing GT-TsF derived from these F1 hybrid mice is able to induce second-order suppressor cells (Ts2). This is consistent with the observation that injection of GT-TsF1 derived from C57BL/6 (I-Jb) mice into A/J (I-Jk) mice leads to the production of an antigen-specific I-Jk GT-TsF2. Our results suggest that Is gene complementation occurs through a different cellular mechanism that was previously observed for Ir gene complementation. Further, we show that complementing (non-suppressor X nonsuppressor)F1 hybrid mice produce an I-Jb (and not an I-Jk) GT-TsF1 and an I-Jk (not an I-Jb) GT-TsF2, thus suggesting a heterogeneity of Ia loci within the I-J subregion. Data presented in the present study suggest that there may be even more heterogeneity within the I-J subregion than has has been heretofore reported with regard to I-J expression on Ts.

Gain/loss of poly(Glu50Tyr50)/poly(Glu60Ala30Tyr10) responsiveness in the bm12 mutant strain.

The development of inbred strains of mutant mice has proven useful in ascribing specific gene functions to particular genetic loci within the regions and subregions of the H-2 complex. The B6.C-H-2bm12 (bm12) strain is of particular interest in that, compared to parental C57Bl/6Kh (B6) mice, it bears a presumptive single gene mutation altering the Ab beta chain encoded by the I-A subregion. Our data show that bm12 mice have gained the ability to respond to poly(Glu50Tyr50)(GT) and have lost the ability to make plaque-forming cell or delayed-type hypersensitivity responses to the closely related copolymer, poly(Glu60Ala30Tyr10)(GAT), although retaining the ability to mount a GAT-specific T cell proliferative response. This is in sharp contrast to the parental B6 strain, which is a GT nonresponder and a GAT responder. Thus, this study is the first to report the establishment of responder status as a consequence of mutation. Possible mechanisms accounting for the gain/loss of GT/GAT responsiveness in the context of a two-step helper T cell model are discussed.

Inhibition of group A streptococcal infection by Melaleuca alternifolia (tea tree) oil concentrate in the murine model.

AIMS: To investigate the effect of a water-soluble Melaleuca alternifolia concentrate (MAC) on group A streptococcus (GAS; Streptococcus pyogenes)-induced necrotizing fasciitis. METHODS AND RESULTS: MAC pretreatment (1% and 2% v/v) was able to protect mice from GAS infection in an air pouch model. GAS-induced mouse death and skin injury were inhibited dose dependently by MAC. Administration of MAC at 6 h post-GAS infection partially delayed mouse death. Surveys of the exudates of the air pouch of MAC-treated mice revealed that the survival of infiltrating cells was prolonged, the bacteria were eliminated, and the production of inflammatory cytokines was inhibited. MAC could directly inhibit the growth of GAS in vitro, and the minimal inhibitory concentration (MIC) of MAC for GAS was determined as 0.05% v/v using the time-kill assay. Furthermore, a sub-MIC dose of MAC not only enhanced the bactericidal activity of RAW264.7 macrophage cells against GAS but also increased susceptibility of GAS for blood clearance. CONCLUSIONS: These results suggest that MAC may inhibit GAS-induced skin damage and mouse death by directly inhibiting GAS growth and enhancing the bactericidal activity of macrophages. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide scientific data on the use of MAC for the treatment of GAS-induced necrotizing fasciitis in the murine model.

Analysis of the typical unified lattice Boltzmann models and a comprehensive multiphase model for convection-diffusion problems in multiphase systems.

The present paper analyzes the typical unified lattice Boltzmann (LB) models for different convection-diffusion (CD) problems in multiphase systems. The CD problems in multiphase systems can be roughly classified into three groups: CD problems with a continuous scalar value and a continuous flux, a discontinuous scalar value and a continuous flux, a continuous scalar value and a discontinuous flux. The characteristics of the corresponding unified LB models for the three kinds of CD problems are analyzed and the equivalence between the LB models based on different perspectives or numerical schemes is revealed. Finally, a comprehensive multiphase LB model (CMLBM) capable of solving different isotropic and anisotropic CD problems in multiphase systems is proposed. Four typical CD problems in multiphase systems are calculated to validate the CMLBM; the results show that it performs well against the typical isotropic and anisotropic CD problems in multiphase systems.

Suppression of p38 mitogen-activated protein kinase inhibits hepatitis B virus replication in human hepatoma cell: the antiviral role of nitric oxide.

The role of the p38 mitogen-activated protein kinase (MAPK) pathway in hepatitis B virus (HBV) replication was investigated in this study. After transient transfection with HBV plasmid, p38 MAPK, but not JNK or ERK1/2, was significantly phosphorylated in human hepatoma cell Huh7. Interestingly, HBV proteins and RNA synthesis were significantly inhibited by a specific inhibitor of p38 MAPK, SB203580, in a dose-dependent manner. Intracellular core-associated DNA, extracellular virion-associated DNA and covalently closed circular DNA were also significantly inhibited by SB203580. Further results showed the antiviral role of nitric oxide (NO) on the suppression of HBV replication and downregulation of p38 MAPK phosphorylation. In conclusion, these results suggested that suppression of phosphorylation of p38 MAPK by inhibitor or NO could inhibit intracellular HBV replication.

Autophagy induction in T cell-independent acute hepatitis induced by concanavalin A in SCID/NOD mice.

Concanavalin A (Con A) is known to induce acute hepatitis that is mediated by activation of NKT and T-cell and cytokine production in immunocompetent mice. The observation of Con A-induced autophagic cell death of hepatoma cells via a Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 mediated autophagic pathway made us re-evaluate the effect of Con A-induced hepatitis in mice. Con A was administrated intravenously to BABL/c, SCID, or SCID/NOD mice at doses of 20, 30 or 40 mg/kg, respectively, to induce acute hepatitis. The levels of hepatitis and autophagy induction were both analyzed. We found that Con A can induce acute hepatitis in SCID or SCID/NOD mice with kinetics similar to that of BALB/c, but requiring a higher dose of Con A. No lymphocyte infiltrations were found in SCID or SCID/NOD mice, and the cytokine productions were different. An autophagy with microtubule-associated protein light chain 3-II conversion was demonstrated in the liver post-Con A injection in SCID/NOD mice. Due to the mannose/glucose-specific binding on cell membrane, Con A can induce a T-cell-independent acute hepatitis with autophagy in SCID/NOD mice.

Cerebrospinal fluid cytokines in enterovirus 71 brain stem encephalitis and echovirus meningitis infections of varying severity.

Taiwan has experienced several outbreaks of enterovirus 71 (EV71) infections since 1998. This study examined the quantitative relationship between specific cytokines in the cerebrospinal fluid (CSF) and the severity of EV71 brain stem encephalitis (BE), and investigated whether the CSF cytokine response differed from that to uncomplicated echovirus meningitis (EM). The study included 57 children with EV71 BE, of whom 24 had isolated BE, 24 had autonomic nervous system (ANS) dysregulation, and nine had pulmonary oedema (PE), and 15 children with EM. All were confirmed by virus culture. Mean CSF glucose, total protein and lactate levels were increased significantly in association with the severity of EV71 BE. The mean CSF concentration of interleukin (IL)-1beta in children with EV71 PE was significantly higher than in those with isolated BE. IL-6 and interferon (IFN)-gamma levels were significantly higher for EV71 PE and ANS dysregulation than for isolated BE. In contrast, EM was associated with high levels of IL-1beta and low levels of IFN-gamma. Cytokines in the central nervous system, as well as in blood, appear to be involved in the pathogenesis of EV71 BE.

Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family.

A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of alpha 1-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leucine zipper" and its associated DNA-binding domains, while their sequences outside these domains and the sizes of their mRNAs are different. Unlike the limited expression of C/EBP in tissues and cells, AGP/EBP appears to be ubiquitously expressed in tissues like lung, spleen, kidney, heart, testis, and liver and cell lines like p388D1, 129P (hepatoma cell line of C3H/HeJ), FO (mouse myeloma), and L929. Antibody against cloned and expressed AGP/EBP which was raised in rabbits could recognize AGP/EBP from nuclear extract of a number of cells and tissues. On the basis of our findings about the structural relationship and the similarity of motif recognition, we propose that a family of C/EBP-like transcription factors exists.

Purification and characterization of nucleolin and its identification as a transcription repressor.

Expression of the acute-phase response genes, such as that for alpha-1 acid glycoprotein (AGP), involves both positive and negative transcription factors. A positive transcription factor, AGP/EBP, and a negative transcription factor, factor B, have been identified as the two most important factors responsible for the induction of the AGP gene. In this paper we report the purification, characterization, and identification of a B-motif-binding factor from the mouse hepatoma cell line 129p. The purified factor has been identified as nucleolin by amino acid sequence analysis. Biochemical and functional studies further established that nucleolin is a transcription repressor for regulation of AGP and possibly other acute-phase response genes. Thus, in addition to the many known functions of nucleolin, such as rRNA transcription, processing, ribosome biogenesis, and the shuttling of proteins between the cytoplasmic and nuclear compartments, it may also function as a transcriptional repressor.

The potential of soybean foods as a chemoprevention approach for human urinary tract cancer.

Isoflavones are excreted in human urine and can be modulated by soy-rich diets. Recently, isoflavones were suggested to have protective effects against bladder cancer cells. We sought to determine the efficacy of the antitumorigenic effects of isoflavones at concentrations found in the range of human urine excretion and compare normal urothelium and bladder cancer cells for differential cytotoxicity. A total of seven human bladder cancer cell lines and an immortalized uroepithelial cell line were used to examine the effects of genistein, daidzein, and biochanin-A, either individually or as an equal-proportion mixture regimen, on cell growth, DNA synthesis, alterations of cell cycle distribution, and induction of apoptosis. The role of cyclin B1 and cdc2 kinase in cell cycle arrest was analyzed. In addition, severe combined immunodeficient mice were used to confirm the anti-cancer effects of isoflavones in vivo. Cooperative action of isoflavones was more effective in growth inhibition and apoptosis induction than any single compound. Genistein tends to cause a dose-dependent induction of G2-M cell cycle arrest and an inhibition of cdc2 kinase activity. However, both daidzein and biochanin-A directly induced apoptosis without altering cell cycle distribution. The IC50 values in non-transformed cells were higher than those in most cancer cell lines, and the IC50 of the mixture regimen was within reach of the levels observed in urine after a soy challenge. Furthermore, both genistein and combined isoflavones exhibited a significant tumor suppressor effect in vivo (P < 0.05). The results justify the potential use of soybean foods as a practical chemoprevention approach for patients with urinary tract cancer.

Induction of antitumor immunity with combination of HER2/neu DNA vaccine and interleukin 2 gene-modified tumor vaccine.

The therapeutic effects of both cytokine-secreting tumor vaccine and DNA vaccine were studied using mouse MBT-2 bladder cancer cells as a model. Cytokine-secreting MBT-2 cells were obtained by infecting cells with retroviral particles containing interleukin (IL) 2-, IL-4-, or granulocyte-macrophage colony-stimulating factor (GM-CSF)-expression vector. The MBT-2-IL-2 cells were not tumorigenic in syngenic C3H mice at all. Tumor formation decreased significantly for the MBT-2-GM-CSF cells. MBT-2-IL-2, -IL-4, and -GM-CSF cells were killed by irradiation and tested as tumor vaccines. The irradiated MBT2-IL-2 cells could complete protect mice from the growth of the preexisting tumor cells, and the immune memory lasted for 8 months. On the other hand, irradiated MBT-2-IL-4 and MBT-2-GM-CSF cells were less effective. When the loading tumor mass increased, all tumor vaccines lost protective effects. DNA vaccine encoding the tumor antigen neu was additionally tested to improve the therapeutic efficacy. Coinjection of 60 microg pSV-neu DNA was effective in enhancing the antitumor effects of MBT2-IL-2; however, DNA vaccine alone cannot prevent the progression of the preexisting tumor. Immunohistochemical analysis of tumor infiltrate revealed massive increase of CD4+ lymphoid cells in the group of mice treated with both DNA vaccine and IL-2-secreted tumor vaccine. Western blotting demonstrated the presence of anti-neu antibody in the serum from immunized mice. In contrast, combination of DNA vaccine and MBT-2-GM-CSF has no additive effect. The results indicate the combination of DNA vaccine and IL-2-secreting tumor vaccine can additionally improve therapeutic efficacy, and the efficacy is correlated with the increase of CD4+ T lymphocytes and anti-neu antibody.

Antibody-mediated endothelial cell damage via nitric oxide.

Vascular disorders, resulting from endothelial cell dysfunction, may be caused by various stimuli, including infectious pathogens, cytotoxic reagents, and pathophysiological mechanisms mediated by immune responses. Endothelial cell dysfunction characterized by apoptosis and abnormal immune activation is, at least in part, induced by anti-endothelial cell antibody (AECA) in some cases of autoimmune disease. However, the molecular mechanisms of AECA-mediated pathogenetic damage to host vascular system remain unclear. The dual role of nitric oxide (NO) both in endothelial cell apoptosis and survival has been described. In this paper, endothelial cell apoptosis caused by the presence of cross-reactive AECA via a NO-mediated mechanism is demonstrated in dengue virus infection. Endothelial cells undergo apoptosis via the mitochondria-dependent pathway that is regulated by NO production. NO-regulated endothelial cell injury thus may play a role in the disruption of vessel endothelium and contribute to the AECA-induced pathogenesis of vasculopathy. The modulation of NO may provide the therapeutic strategies for autoimmune diseases by preventing the AECA-mediated endothelial cell damage.

V beta 8+CD4-CD8- subpopulation induced by staphylococcal enterotoxin B.

Injection of staphylococcal enterotoxin B (SEB) into BALB/c mice induced the depletion of V beta 8+ T-cells which were either V beta 8+CD4+ or V beta 8+CD8+ cells. The CD8 molecule on V beta 8+CD8+ cells was found to decrease at 72 h after SEB treatment while the V beta 8 molecule on V beta 8+ cells or CD4 molecule on V beta 8+CD4+ cells was not affected. Furthermore, a subpopulation of V beta 8+CD4-CD8- T-cells was also induced after SEB-priming. This subpopulation can be found in spleen or lymph nodes. It was small in size and constituted the major part of V beta 8+ cells in lymph nodes at 72 h after SEB-priming. Some of the V beta 8+CD4-CD8- T-cells might be autoreactive because they could be stimulated to proliferative by syngenic mitomycin C-treated splenocytes.

Expression of CD40 and CD40 ligand among cell populations within rheumatoid synovial compartment.

Augmented and prolonged expression of CD40 ligand (CD40L) was recently reported in lymphoid cells from human lupus patients, suggesting that CD40/CD40L pathway was involved in the pathogenesis of systemic autoimmune diseases. This study was thus designed to study the expression of CD40 and CD40L among cell populations within inflammatory joints of patients with rheumatoid arthritis (RA). The result showed that most B cells and monocytes in synovial fluids (SF) expressed CD40. Cultured synovial fibroblasts also stained positive for CD40. Regarding CD40L, we found that T cells as well as B cells could express CD40L. Compared with normal controls, RA patients had higher levels of CD40L+ T cells (8.71 +/- 17.69% vs 1.74 +/- 2.30%, P > 0.05) and CD40L+ B cells (7.71 +/- 7.64% vs 1.12 +/- 1.59% P < 0.05). After in vitro stimulation, T cells from RA patients had higher and longer CD40L expression than T cells from normal peripheral blood. For investigating the effect of CD40 expressed on synovial fibroblasts on TNF-alpha production in joint compartment, we used anti-CD40 antibody to bind CD40 on fibroblasts for one hour and then co-cultured with synovial fluid mononuclear cells. We found that the levels of TNF-alpha decreased in the presence of anti-CD40 antibody. We concluded that there was an intrinsic hyperexpression of CD40L on lymphoid cells within rheumatoid joints, and synovial fibroblasts could contribute to articular inflammation through surface CD40 molecule.

Increase of intracellular pH in p53-dependent apoptosis of thymocytes induced by gamma radiation.

Irradiation with gamma rays induces apoptosis of thymocytes by a p53-dependent pathway, but its mechanism is not clear. In this study, we report that gamma-ray-induced apoptosis was associated with the intracellular alkalinization of the thymocytes. After exposure to gamma rays, thymocytes underwent apoptosis when cultured in vitro, and the degree of apoptosis was dependent on the incubation period: The longer the incubation period, the greater the number of cells undergoing apoptosis. However, this apoptosis could be inhibited by the acidic condition of the culture. There was a positive correlation between the pHi of thymocytes and the degree of apoptosis. Treatment with gamma radiation induced apoptosis as well as the elevation of the pHi in thymocytes. The intracellular pH was higher in pre-apoptotic thymocytes than in those that did not undergo apoptosis. Furthermore, apoptosis induced by gamma radiation was inhibited by cycloheximide, actinomycin D or the intracellular Ca2+ chelator, TMB-8. The p53 protein is induced after gamma irradiation. Thus it appears that intracellular pH is increased during the gamma-ray-induced p53-dependent apoptosis of thymocytes.