[Survival and disease burden trend analysis of occupational pneumoconiosis from 1963 to 2020 in Shizuishan City].

Objective: To understand the survival status and its influencing factors of occupational pneumoconiosis patients in Shizuishan City, and to analyze the disease burden of occupational pneumoconiosis and its trend, so as to provide scientific basis for formulating comprehensive prevention and treatment measures of occupational pneumoconiosis. Methods: A retrospective survey was conducted during July to December 2020 to explore the survival status of occupational pneumoconiosis patients who had been reported from 1963 to 2020 in Shizuishan City. The Kaplan-Meier method and Life-table method were used for survival analysis, and Cox proportional hazards regression model was used to analyze the influencing factors of survival time. The disability adjusted life years (DALY) was applied to analyze the disease burden of occupational pneumoconiosis and its temporal trend. Results: From 1963 to 2020, a total of 3263 cases of occupational pneumoconiosis were reported in Shizuishan City, of which 1467 died, so that the fatality rate was 44.96%. The median survival time was 26.71 years, average age of death was (70.55±10.92) years old. There were significant differences in the survival rates of occupational pneumoconiosis patients among different types, diagnosis age, exposure time, industry, initial diagnosis stage and whether upgraded (P<0.05) . As the survival time increased, the survival rate of patients decreased gradually. When the survival time was ≥50 years, the cumulative survival rate of patients was 4.20%. Cox regression analysis suggested that the type of pneumoconiosis, industry, diagnosis age, exposure time, initial diagnosis stage and whether upgraded were the influencing factors for the survival time of patients with occupational pneumoconiosis (P<0.05) . The total DALY attributable to occupational pneumoconiosis from 1963 to 2020 in Shizuishan City was 48026.65 person years, of which the years of life lost (YLL) was 15155.39 person years, and the average YLL was 10.33 years/person, and the years lost due to disability (YLD) was 32871.26 person years, and the average YLD was 10.07 years/person. The DALY attributed to coal worker's pneumoconiosis and silicosis were 39408.51 person years and 6565.02 person years, respectively, and they accounted for 82.06% and 13.67% of the total disease burden in Shizuishan City, respectively. The DALY caused by occupational pneumoconiosis in the age group of 40-49 years old and the first diagnosis of stage I occupational pneumoconiosis were higher, which were 20899.71 and 36231.97 person years, respectively. The average YLL and average YLD showed a volatility downtrend over time. Conclusion: The disease burden of occupational pneumoconiosis cannot be ignored in Shizuishan City, and timely targeted measures should be taken for key populations and key industries. It is recommended that life-cycle health management and hierarchical medical should be taken to improve the life quality of patients and prolong their lifes.

Suppression of HAX-1 induced by miR-325 resensitizes bladder cancer cells to cisplatin-induced apoptosis.

OBJECTIVE: MicroRNA-325 (miR-325) is a tumor suppressor in some cancers. However, the role of miR-325 in determining the chemosensitivity to cancer cells is still not clear. The aim of this study was to investigate the effect of miR-325 on reversing the cisplatin resistance of bladder cancer. MATERIALS AND METHODS: Cisplatin-resistant 5637 and T24 bladder cancer cell lines (5637/R and T24/R) were established through long term exposure of them to cisplatin. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assays were performed to evaluate the viability of 5637, 5637/R, T24, and T24/R cells. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was used to examine the expression of miR-325 in these cell lines. The regulatory mechanism was confirmed by Western blot analysis and Luciferase reporter assays. After treatment with miR-325 and cisplatin, mitochondrial membrane potential (MMP) and apoptosis were measured using flow cytometry. Expression of hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) and activation of caspase-9, caspase-7, and caspase-3 were detected by Western blotting. RESULTS: We found the downregulation of miR-325 in 5637/R and T24/R cells compared to their parental 5637 and T24 cells. Moreover, overexpression of miR-325 in cisplatin-resistant bladder cancer cells was found to increase the cytotoxicity of cisplatin to them. However, transfection with HAX-1 plasmid can abolish the effect of miR-325 on cisplatin. We, then, showed that overexpression of miR-325 suppressed the expression of HAX-1. Thus, miR-325 promoted the mitochondria collapse and cisplatin-induced apoptosis in bladder cancer cells. CONCLUSIONS: Downregulation of miR-325 is responsible for the development of cisplatin resistance in bladder cancer. Overexpression of miR-325 may represent a novel strategy to reverse the chemoresistance of bladder cancer.

[A historical review of general medicine].

The first official general medicine was established in the United States, and society of general medicine established in 1947. After that the European and American countries began to study of general medicine and construct system. In 1966, the commonwealth launched the first global residency training program in general medicine.At present, many countries have formed a perfect general practitioner training system. In 1988, the concept of general medicine was introduced into China. In 1989, the Chinese Medical Association established the General Medicine Education Committee, marked the beginning of general medical education in China. In 1993, General Medicine Branch of Chinese Medical Association was set up, was a symbol of the birth of general medicine in China. Compared with some European and American countries, China's general medicine was a late starter, and the training of general practitioners has experienced the development of diversification, at present, it is in line with the international training mode.

Long non-coding RNA TTN-AS1 promotes cell proliferation and inhibits cell apoptosis in prostatic cancer by sponging miR-193a-5p.

OBJECTIVE: Prostatic cancer (PCa) is a common cancer in males. Long non-coding RNA (lncRNA) TTN-AS1 has been reported as an oncogene in diverse cancers. This study aimed to explore the functions and mechanism of TTN-AS1 in PCa. MATERIALS AND METHODS: The levels of TTN-AS1 and miR-193a-5p in PCa cells (DU145, PC3, 22RV1, C4-2B, and LNCaP) were measured by qRT-PCR. The putative target of TTN-AS1 was predicted by starBase v2.0 online database, and this interaction was validated by Dual-Luciferase reporter assay. The cell viability and apoptosis rate in DU145 and PC3 cells were assessed by MTT assay and flow cytometry, respectively. The protein levels of CyclinD1, p21, p27, Bcl-2, Bax, and cleaved-caspase3 were detected by Western blot. RESULTS: The relative expression of TTN-AS1 was apparently up-regulated, and the level of miR-193a-5p was strikingly down-regulated in PCa cells. The interaction between TTN-AS1 and miR-193a-5p was predicted by starBase v2.0 online database and verified by Dual-Luciferase reporter assay. The functional experiments indicated that TTN-ASI knockdown or miR-193a-5p inhibited cell viability and induced cell apoptosis rate in DU145 and PC3 cells. Furthermore, the recuperated experiments exhibited that miR-193a-5p inhibitor counteracted the inhibitory effect on cell viability and the promotion effect on cell apoptosis rate in DU145 and PC3 cells induced by TTN-AS1 silencing. CONCLUSIONS: These data indicated that TTN-AS1 was dramatically up-regulated, and miR-193a-5p was significantly down-regulated in PCa cells. The functional and mechanistical experiments unraveled that lncRNA TTN-AS1 sponged miR-193a-5p to promote cell proliferation and repress cell apoptosis in prostatic cancer, and this new regulatory pathway may shed light on the mechanism of prostatic cancer.

Association of G-protein ß3 subunit C825T polymorphism with essential hypertension: evidence from 63 729 subjects.

Many studies have reported that G-protein ß3 subunit (GNB3) C825T polymorphism is associated with essential hypertension (EH), although this remains subject to debate. Thus, meta-analysis was carried out to clarify this relationship. A total of 75 articles, reporting 81 case-control studies evaluating 28 369 patients and 34 933 control individuals, were assessed. Overall, a significant association was observed in the dominant model (odds ratio (OR)=1.11, 95% CI 1.04-1.19), recessive model (OR=1.09, 95% CI 1.01-1.17), TT vs CC (OR=1.16, 95% CI 1.05-1.28), CT vs CC (OR=1.09, 95% CI 1.02-1.17), and additive model (OR=1.07, 95% CI 1.02-1.13) after pooling all eligible studies. Subgroup analysis by ethnicity and gender demonstrated significantly increased EH only in Caucasians using the dominant (OR=1.22, 95% CI 1.07-1.39; TT vs CC, OR=1.29, 95% CI 1.07-1.54; CT vs CC, OR=1.19, 95% CI 1.05-1.35) and additive (OR=1.16, 95% CI 1.05-1.28) models. In summary, the present meta-analysis indicated the GNB3 C825T polymorphism is related to increased EH exclusively in Caucasians.

Mental health and related influencing factors among the empty-nest elderly and the non-empty-nest elderly in Taiyuan, China: a cross-sectional study.

OBJECTIVE: In China, elderly make up a large proportion of the society, but their mental health is often overlooked. The aim of this study is to compare mental health and related influencing factors among the empty-nest and the non-empty-nest elderly, and attain the purpose of improving their quality of life. STUDY DESIGN: Cross-sectional survey. METHODS: A cross-sectional survey was conducted among 488 elderly people aged 60-92 years in six districts of Taiyuan, China. A demographic questionnaire and SCL-90-R were employed to collect demographic variables and evaluate mental health, respectively. Multiple regression analysis was performed to estimate factors related to mental health of the elderly. RESULTS: The empty-nest elderly were mostly male, married, higher education level, higher income and living in urban areas. The scores of SCL-90-R among the empty-nest elderly were lower than those of the non-empty-nest elderly except for psychoticism. Comparing with scores of national norms, some dimension of SCL-90-R had statistically significant differences. Multiple regression analysis showed that the main risk factors of the empty-nest elderly were gender and income, whereas the main risk factor of the non-empty-nest elderly was chronic diseases. CONCLUSION: The mental health status of the empty-nest elderly was better than that of the non-empty-nest elderly. Overall mental health of the study population was at a high level compared with national norms. The elderly who were male, with younger age, having higher income, and without chronic diseases had better mental health status.

Adsorption of phenolic compounds from aqueous solution onto a macroporous polymer and its aminated derivative: isotherm analysis.

Adsorption of phenolic compounds from aqueous solution to a macroporous polymeric adsorbent (CHA-111), its animated derivative (MCH-111) and a reference weakly anion exchanger (ND-900) was studied. Experimental results indicated that amino functional groups on the polymeric matrix play an important role in phenol adsorption by MCH-111 and ND-900, which was attributed to the formation of hydrogen bonding between the phenol molecule and the amino group on the polymeric matrix. The semi-empirical Freundlich isotherm equation and its reduced form were employed to interpret the adsorption behavior. A site energy distribution model based on the Polanyi adsorption potential theory can elucidate the adsorption mechanism reasonably.

Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1.

The phosphatidylinositol 3-kinase (PI3K) signaling pathway has inherent oncogenic potential. It is up-regulated in diverse human cancers by either a gain of function in PI3K itself or in its downstream target Akt or by a loss of function in the negative regulator PTEN. However, the complete consequences of this up-regulation are not known. Here we show that insulin and epidermal growth factor or an inactivating mutation in the tumor suppressor PTEN specifically increase the protein levels of hypoxia-inducible factor (HIF) 1alpha but not of HIF-1beta in human cancer cell lines. This specific elevation of HIF-1alpha protein expression requires PI3K signaling. In the prostate carcinoma-derived cell lines PC-3 and DU145, insulin- and epidermal growth factor-induced expression of HIF-1alpha was inhibited by the PI3K-specific inhibitors LY294002 and wortmannin in a dose-dependent manner. HIF-1beta expression was not affected by these inhibitors. Introduction of wild-type PTEN into the PTEN-negative PC-3 cell line specifically inhibited the expression of HIF-1alpha but not that of HIF-1beta. In contrast to the HIF-1alpha protein, the level of HIF-1alpha mRNA was not significantly affected by PI3K signaling. Vascular endothelial growth factor reporter gene activity was induced by insulin in PC-3 cells and was inhibited by the PI3K inhibitor LY294002 and by the coexpression of a HIF-1 dominant negative construct. Vascular endothelial growth factor reporter gene activity was also inhibited by expression of a dominant negative PI3K construct and by the tumor suppressor PTEN.

Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells.

Phosphatidylinositol 3-kinase (PI 3-kinase) is a signaling molecule that controls numerous cellular properties and activities. The oncogene v-p3k is a homolog of the gene coding for the catalytic subunit of PI 3-kinase, p110alpha. P3k induces transformation of cells in culture, formation of hemangiosarcomas in young chickens, and myogenic differentiation in myoblasts. Here, we describe a role of PI 3-kinase in angiogenesis. Overexpression of the v-P3k protein or of cellular PI 3-kinase equipped with a myristylation signal, Myr-P3k, can induce angiogenesis in the chorioallantoic membrane (CAM) of the chicken embryo. This process is characterized by extensive sprouting of new blood vessels and enlargement of preexisting vessels. Overexpression of the myristylated form of the PI 3-kinase target Akt, Myr-Akt, also induces angiogenesis. Overexpression of the tumor suppressor PTEN or of dominant-negative constructs of PI 3-kinase inhibits angiogenesis in the yolk sac of chicken embryos, suggesting that PI 3-kinase and Akt signaling is required for normal embryonal angiogenesis. The levels of mRNA for vascular endothelial growth factor (VEGF) are elevated in cells expressing activated PI 3-kinase or Myr-Akt. VEGF mRNA levels are also increased by insulin treatment through the PI 3-kinase-dependent pathway. VEGF mRNA levels are decreased in cells treated with the PI 3-kinase inhibitor LY294002 and restored by overexpression of v-P3k or Myr-Akt. Overexpression of VEGF by the RCAS vector induces angiogenesis in chicken embryos. These results suggest that PI 3-kinase plays an important role in angiogenesis and regulates VEGF expression.

Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium.

Gustducin is a transducin-like G protein selectively expressed in taste receptor cells. The alpha subunit of gustducin (alpha-gustducin) is critical for transduction of responses to bitter or sweet compounds. We identified a G-protein gamma subunit (Ggamma13) that colocalized with alpha-gustducin in taste receptor cells. Of 19 alpha-gustducin/Ggamma13-positive taste receptor cells profiled, all expressed the G protein beta3 subunit (Gbeta3); approximately 80% also expressed Gbeta1. Gustducin heterotrimers (alpha-gustducin/Gbeta1/Ggamma13) were activated by taste cell membranes plus bitter denatonium. Antibodies against Ggamma13 blocked the denatonium-induced increase of inositol trisphosphate (IP3) in taste tissue. We conclude that gustducin heterotrimers transduce responses to bitter and sweet compounds via alpha-gustducin's regulation of phosphodiesterase (PDE) and Gbetagamma's activation of phospholipase C (PLC).

Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B.

The oncogene p3k, coding for a constitutively active form of phosphatidylinositol 3-kinase (PI 3-kinase), strongly activates myogenic differentiation. Inhibition of endogenous PI 3-kinase activity with the specific inhibitor LY294002, or with dominant-negative mutants of PI 3-kinase, interferes with myotube formation and with the expression of muscle-specific proteins. Here we demonstrate that a downstream target of PI 3-kinase, serine-threonine kinase Akt, plays an important role in myogenic differentiation. Expression of constitutively active forms of Akt dramatically enhances myotube formation and expression of the muscle-specific proteins MyoD, creatine kinase, myosin heavy chain, and desmin. Transdominant negative forms of Akt inhibit myotube formation and the expression of muscle-specific proteins. The inhibition of myotube formation and the reduced expression of muscle-specific proteins caused by the PI 3-kinase inhibitor LY294002 are completely reversed by constitutively active forms of Akt. Wild-type cellular Akt effects a partial reversal of LY294002-induced inhibition of myogenic differentiation. This result suggests that Akt can substitute for PI 3-kinase in the stimulation of myogenesis; Akt may be an essential downstream component of PI 3-kinase-induced muscle differentiation.

An essential role of phosphatidylinositol 3-kinase in myogenic differentiation.

The oncogene p3k, coding for a constitutively active form of phosphatidylinositol 3-kinase (PI 3-kinase; EC 2.7.1.137), strongly enhances myogenic differentiation in cultures of chicken-embryo myoblasts. It increases the size of the myotubes and induces elevated levels of the muscle-specific proteins MyoD, myosin heavy chain, creatine kinase, and desmin. Inhibition of PI 3-kinase activity with LY294002 or with dominant-negative mutants of PI 3-kinase interferes with myogenic differentiation and with the induction of muscle-specific genes. PI 3-kinase is therefore an upstream mediator for the expression of the muscle-specific genes and is both necessary and rate-limiting for the process of myogenesis.

Mammalian male and female germ cells express a germ cell-specific Y-Box protein, MSY2.

Here we report the isolation and characterization of mouse testicular cDNAs encoding the mammalian homologue of the Xenopus germ cell-specific nucleic acid-binding protein FRGY2 (mRNP3+4), hereafter designated MSY2. MSY2 is a member of the Y box multigene family of proteins; it contains the cold shock domain that is highly conserved among all Y box proteins and four basic/aromatic islands that are closely related to the other known germline Y box proteins from Xenopus, FRGY2, and goldfish, GFYP2. Msy2 undergoes alternative splicing to yield alternate N-terminal regions upstream of the cold shock domain. Although MSY2 is a member of a large family of nucleic acid-binding proteins, Southern blotting detects only a limited number of genomic DNA fragments, suggesting that Msy2 is a single copy gene. By Northern blotting and immunoblotting, MSY2 appears to be a germ cell-specific protein in the testis. Analysis of Msy2 mRNA expression in prepubertal and adult mouse testes, and in isolated populations of germ cells, reveals maximal expression in postmeiotic round spermatids, a cell type with abundant amounts of stored messenger ribonucleoproteins. In the ovary, MSY2 is present exclusively in diplotene-stage and mature oocytes. MSY2 is maternally inherited in the one-cell-stage embryo but is not detected in the late two-cell-stage embryo. This loss of MSY2 is coincident with the bulk degradation of maternal mRNAs in the two-cell embryo.

Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tension.

Hypoxia-inducible factor 1 (HIF-1) binds to cis-acting hypoxia-response elements within the erythropoietin, vascular endothelial growth factor, and other genes to activate transcription in hypoxic cells. HIF-1 is a basic helix-loop-helix transcription factor composed of HIF-1alpha and HIF-1beta subunits. Here, we demonstrate that HIF-1alpha contains two transactivation domains located between amino acids 531 and 826. When expressed as GAL4 fusion proteins, the transcriptional activity of these domains increased in response to hypoxia. Fusion protein levels were unaffected by changes in cellular O2 tension. Two minimal transactivation domains were localized to amino acid residues 531-575 and 786-826. The transcriptional activation domains were separated by amino acid sequences that inhibited transactivation. Deletion analysis demonstrated that the gradual removal of inhibitory domain sequences (amino acids 576-785) was associated with progressively increased transcriptional activity of the fusion proteins, especially in cells cultured at 20% O2. Transcriptional activity of GAL4/HIF-1alpha fusion proteins was increased in cells exposed to 1% O2, cobalt chloride, or desferrioxamine, each of which also increased levels of endogenous HIF-1alpha protein but did not affect fusion protein levels. These results indicate that increased transcriptional activity mediated by HIF-1 in hypoxic cells results from both increased HIF-1alpha protein levels and increased activity of HIF-1alpha transactivation domains.

Effects of exogenous gangliosides on learning and memory in rats.

After 10 or more consecutive daily injections (I.P. 50 mg/kg for developing, adult and aged, 2.5 mg/mouse for neonatal) of total bovine gangliosides, rats were trained to perform the discrimination tasks. The results show that gangliosides can enhance the learning ability and memory retention in rats at different ages.