Evidence for causal effects of neuropsychiatric conditions on risk of venous thromboembolism: A univariable and multivariable Mendelian randomization study.

BACKGROUND: Substantial observational evidence suggests an association between neuropsychiatric conditions and venous thromboembolism (VTE). However, the causal relationship between these two conditions requires further investigation. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the bidirectional causal effects between four neuropsychiatric conditions and VTE, deep vein thrombosis, and pulmonary embolism (PE). METHODS: Genetic variants associated with four neuropsychiatric conditions (ie, schizophrenia, major depressive disorder [MDD], bipolar disorder, and epilepsy) and VTE, deep vein thrombosis, and PE were selected. Bidirectional univariable and multivariable MR methods were applied to evaluate the causal relationships among these conditions. The primary causal estimates were obtained using the inverse variance weighted method with multiplicative random effects, supplemented by MR Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analysis was conducted using the MR pleiotropy residual sum, funnel plots, and outlier (MR pleiotropy and residual sum and outlier) method. RESULTS: Univariable MR results showed that genetic susceptibility to MDD increases the risk of VTE and PE (VTE: odds ratio [OR], 1.25; 95% confidence interval [CI], 1.08-1.46; P = .004; PE: OR, 1.36; 95% CI, 1.09-1.69; P = .006) and that PE has an adverse causal effect on MDD (OR, 1.02; 95% CI, 1.00-1.04; P = .026). Adjustment for confounders such as obesity, sleep duration, smoking, physical activity, and alcohol consumption revealed that increased genetic susceptibility to MDD is also associated with VTE and PE. CONCLUSIONS: Our results suggest that genetic susceptibility to MDD might have an adverse causal effect on the risk of VTE and PE and that PE has a reverse causal effect on MDD. Prevention and early diagnosis of depression are crucial in the management of VTE and PE.

[Research progress in radiotherapy for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China with high morbidity and mortality, and its mortality rate is only lower than that of gastric cancer. It poses a serious threat to patients' life, which needs to be given special concerns by clinicians and patients for active implementation of effective treatment methods. Generally, major operation is the mainstay of management. Radiotherapy has gained its popularity when diagnosed have no indications for surgical therapy. An effective radiotherapy plans promote the remission of hepatocellular carcinoma to improve patients condition, prognosis, and survival rate. Therefore, we conducted this study to know the research progress of radiotherapy for hepatocellular carcinoma.

Inhibition of titanium particle-induced inflammatory osteolysis through inactivation of cannabinoid receptor 2 by AM630.

Wear particle could induce inflammatory osteolysis and is the primary pathological factor for aseptic loosening. Although it is known that cannabinoid receptor 2 (CB2) inhibits osteoclast differentiation, the effect on inflammatory osteolysis induced by wear particles remains unclear. This study examined the effect of CB2 in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which has been shown to be stimulated by titanium (Ti) particles and receptor activator of the NF-kappaB ligand (RANKL). Results showed that CB2 expression in RAW cells cultured with Ti particles and RANKL. CB2 inactivation by AM630, a CB2 selective antagonist, effectively inhibited osteoclastogenesis in the differentiation medium system. AM630 treatment (> or =100 nM) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells when compared with the control. Real-time reverse transcription polymerase chain reaction analysis revealed that AM630 (100 nM) inhibited mRNA expression of RANK and cathepsin K in RAW cells stimulated by Ti particles and RANKL. Moreover, enzyme-linked immunosorbent assay showed that AM630 (100 nM) reduced protein expression of interleukin-1beta and tumor necrosis factor-alpha in RAW cells cultured with Ti particles. In addition, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide revealed that AM630 had no toxic effect on RAW cells. These results suggested that CB2 inactivation by AM630 could provide a promising therapeutic target for treating or preventing aseptic loosening.

Diversity analysis of antagonists from rice-associated bacteria and their application in biocontrol of rice diseases.

AIMS: To understand the diversity, taxonomy and antagonistic potential of rice-associated bacteria, and to discover new bacteria for biocontrol of rice foliar pathogens. METHODS AND RESULTS: Amplified ribosomal DNA restriction analysis (ARDRA), BOX-PCR and 16S rRNA gene sequence analysis were used to identify the diversity of 203 rice-associated antagonistic bacteria. Eleven potential biocontrol bacteria were used to test their biological control of rice blast in a natural field experiment. Eleven different genera were encountered in five divisions, including Bacilli, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and Deinococci. The most prominent genus in all microenvironments was Bacillus (68 x 5%). The efficacy of rice leaf blast biocontrol was 64 x 35% for strain 1Pe2, 57 x 86% for strain 2R37 and 56 x 44% for strain 1Re14. CONCLUSIONS: Biocontrol data from the field experiments demonstrated no positive correlation between antagonism, physiological characteristics and biocontrol efficacy. There was significant diversity among the rice-associated bacteria isolated from different microenvironments. The most prominent genus of all microenvironments was Bacillus. Brevibacillus brevis strain 1Pe2 and Deinococcus aquaticus strain 1Re14 have good potential for field application and commercial use. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first attempt to study the diversity and identification of rice-associated antagonistic bacteria from different microenvironments, and endophytic bacteria Deinococcus aquaticus strain 1Re14, Acidovorax sp. isolate 3Re21 and Brevibacillus brevis strain 1Pe2 are first reported as rice-associated bacteria.

Neuroendocrine differentiation in 32 cases of so-called sclerosing hemangioma of the lung: identified by immunohistochemical and ultrastructural study.

Thirty-two cases of so-called sclerosing hemangioma of the lung observed by light microscopy were further studied by electron microscopy and/or immunohistochemistry. Three histologic patterns were seen: hemangioma-like, papillary, and solid. The only significant component representing the nature of the lesion is characteristic round cells within the stroma in all these patterns, whereas the surface cells lining the papillary projections or cystic spaces are normal or are hyperplastic bronchioloalveolar cells with a few neuroendocrine cells. Immunohistochemical findings showed that the "stromal cells" (tumor cells) were positive for neuroendocrine markers, namely, chromogranin A (19 of 22 cases), neuron-specific enolase (24 of 24), synaptophysin (six of 10), adrenocorticotropic hormone (14 of 15), growth hormone (14 of 15), calcitonin (11 of 15), and gastrin (11 of 14). Besides, some tumor cells were positive for epithelial membrane antigen (four of four), carcinoembryonic antigen (one of four), and vimentin (one of one). All tumor cells were negative for polyclonal antikeratin antibody (25 cases), AE1 (one case), and AE3 (one case). However, in contrast to the "stromal cells," the surface cells of the cystic spaces stained positively for keratin (25 of 25 cases), AE1 (one of one), AE3 (one of one), epithelial membrance antigen (four of four), and carcinoembryonic antigen (four of four); only a few of them expressed neruoendocrine markers. Both surface and tumor cells were negative for factor VIII-related antigen (25 cases), CD31 (one case), and alpha1-antitrypsin (25 cases). Ten cases further studied by electron microscopy and six examined by ultrastructural morphometry showed that the surface cells were mainly type 2 pneumocytes containing many lamellar bodies in the cytoplasm. Lying among them, neuroendocrine cells were occasionally seen. The stromal tumor cells had no lamellar body, but dense core granules (neurosecretory granules) and microtubules. In six cases, 92.3% (345 of 374) of tumor cells contained neurosecretory granules, which were pleomorphic and 73 to 1056 nm in diameter (mean, 302 nm). Two to 193 (mean, 12) neurosecretory granules were found in each tumor cell. Both immunohistochemical findings and ultrastructural evidence indicate that so-called sclerosing hemangioma of the lung is a benign lesion composed of neoplastic neuroendocrine cells with areas of sclerosis. A suggested name for this tumor is benign neuroendocrine tumor of the lung. The differentiation between this tumor and papillary adenoma, bronchioloalveolar carcinoma, or carcinoid tumor of the lung is discussed.

[Biologic effects of hyperthermia and radiation on gastric cancer cells (SGC-7901) in vitro. II. Ultrastructural changes of cells].

Different characteristic damages of the SGC-7901 gastric adenocarcinoma cells were studied by electron microscopy 1, 36, 72, 96 and 120 hours after heating and radiation in vitro. The visible damages, such as the enlarged mitochondria, increase of lysosomes and perichromatin granules could be shown 1 hour after heating (43 degrees C for 30 min) but no visible damages of the cells were shown until 36 hours following radiation (500 rad). In order to study the ultrastructural changes of the gastric cancer cells in mitosis after heating and radiation, we have used the new method of ultrastructural research in selecting and observing the M cell in vitro and found loosened structure of chromosome and disappearance of microtubules 1 hour following hyperthermia. At the same time, no apparent abnormalities of the mitotic cells were observed after radiation. It is the chief cause of division delay in heat injured cells. However, the chromosomes and microtubules of the new mitotic cells could recover 36 hours after heating (43 degrees C for 30 min). After radiation, the giant cells and abnormal morphologic changes of cells gradually increase and the living cells decrease. Unexpectedly, the division of a few giant cells is observed 72 hours after heating and radiation.