Does information disclosure among public hospitals stimulate medical cost change efforts? A pilot study in Shanghai.

BACKGROUND: In 2013, the Shanghai Hospital Development Center issued a policy to advocate public hospitals to report their information about costs on diseases. The objective was to evaluate the impact of interhospital disclosure of costs on diseases on medical costs and compare costs per case following information disclosure between hospitals of different rankings. METHODS: The study uses the hospital-level performance report issued by Shanghai Hospital Development Center in the fourth quarter of 2013, which covers quarterly aggregated hospital-level discharge data from 14 tertiary public hospitals participating in thyroid malignant tumors and colorectal malignant tumors information disclosure from the first quarter of 2012 to the third quarter of 2020. An interrupted time series model with segmented regression analysis is employed to examine changes in quarterly trends with respect to costs per case and length of stay before and after information disclosure. We identified high- and low-cost hospitals by ranking them on a costs per case basis per disease group. RESULTS: This research identified significant differences in cost changes for thyroid malignant tumors and colorectal malignant tumors between hospitals after disclosing information. A hospital's discharge costs per case for thyroid malignant tumors increased significantly among top-cost hospitals (1629.251 RMB, P = 0.019), while decreased for thyroid and colorectal malignant tumors among low-cost hospitals (-1504.189 RMB, P = 0.003; -6511.650 RMB, P = 0.024, respectively). CONCLUSION: Our findings indicate that information disclosure of costs on diseases results in changes in discharge costs per case. And low-cost hospitals continued to maintain their leading edge, whereas the high-cost hospitals changed their position in the industry by reducing discharge costs per case after information disclosure.

'Immunomers'--novel 3'-3'-linked CpG oligodeoxyribonucleotides as potent immunomodulatory agents.

Oligodeoxyribonucleotides containing CpG dinucleotides (CpG DNAs) are currently being evaluated as novel immunomodulators in clinical trials. Recently, we showed that an accessible 5' end is required for immunostimulatory activity and blocking the 5' end of CpG DNA by conjugation of certain ligands abrogates immunostimulatory activity. Based on these results, we designed and synthesized 3'-3'-linked CpG DNAs that contained two or more identical CpG DNA segments, referred to here as 'immunomers'. The use of solid support bearing diDMT-glyceryl-linker permitted convenient synthesis of immunomers with both segments synthesized simultaneously, giving better yields and purity. The in vitro and in vivo studies suggest that as a result of accessibility to two 5' ends for recognition, immunomers show an enhanced immunostimulatory activity compared with linear CpG DNAs. We also studied the suitability of a number of different linkers for attaching the two segments of immunomers. A C3-linker was found to be optimal for joining the two segments of immunomers. Incorporation of multiple linkers between the two segments of immunomers resulted in different cytokine profiles depending on the nature and number of linkers incorporated. Additionally, the length of immunomer also plays a significant role in inducing immune responses. An immunomer containing 11 nt in each segment showed the highest activity and an 11mer linear CpG DNA failed to stimulate an immune response. These results suggest that immunomers have several advantages over conventional linear CpG DNAs for immunomodulatory activity studies.

Design, synthesis, and immunostimulatory properties of CpG DNAs containing alkyl-linker substitutions: role of nucleosides in the flanking sequences.

Bacterial and synthetic DNA containing unmethylated CpG dinucleotides activate the innate immune system and promote Th1-like immune responses. Recently, a receptor, TLR9, has been shown to recognize CpG DNA and activate immune cascade. But there have been no reports on the molecular mechanisms of recognition between CpG DNA and the receptor(s). Our earlier studies described a number of the chemical and structural characteristics of CpG dinucleotide and the sequences flanking the CpG dinucleotide that are critical for immunostimulatory activity. In the present study, we examined the effect of the presence and absence of a nucleoside in the flanking sequences by replacing one or two natural deoxyribonucleosides at various positions with one or more alkyl- (C2-C12), branched alkyl- (glyceryl or aminobutyryl-propanediol), or ethyleneglycol- (tri or hexa) linkers. The results suggest that a linker substitution at the first two nucleoside positions adjacent to the CpG dinucleotide on the 5'- or the 3'-side neutralizes the immunostimulatory activity, as determined by in vitro mouse spleen cell proliferation, cytokine secretion, and in vivo mouse spleen enlargement. The same substitutions placed about three to six nucleotides away from the CpG dinucleotide either did not affect or potentiated immunostimulatory activity compared with parent CpG-DNA without modifications. Substitution of deoxyribonucleosides with a C3 or C4 alkyl-linker was found to be optimal for potentiating immunostimulatory activity.

Neuroprotective effects of gallic acid against hypoxia/reoxygenation-induced mitochondrial dysfunctions in vitro and cerebral ischemia/reperfusion injury in vivo.

Oxidative stress and mitochondrial dysfunction are frequently implicated in the pathology of secondary neuronal damage following cerebral ischemia/reperfusion. Recent evidence suggests that gallic acid (GA) reverses oxidative stress in rat model of streptozotocin-induced dementia, but the roles and mechanisms of GA on cerebral ischemia/reperfusion injury remain unknown. Here we investigated the potential roles and mechanisms of GA in hypoxia/reoxygenation induced by sodium hydrosulfite (Na2S2O4) in vitro and cerebral ischemia/reperfusion induced by middle cerebral artery occlusion (MCAO) in vivo. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazol carbocyanine iodide (JC-1), Dichlorofluorescin diacetate (DCF-DA) and MitoSOX fluorescent assay, Clark-type oxygen electrode, firefly luciferase assay, and calcium-induced mitochondrial swelling were conducted to detect cell death, mitochondrial membrane potential (MMP), intracellular and mitochondrial reactive oxygen species (ROS), oxygen consumption, ATP level, and mitochondrial permeability transition pore (MPTP) viability. We firstly find that modulation of the mitochondrial dysfunction is an important mechanism by GA attenuating hypoxia/reoxygenation insult. To further assess the effects of GA on cerebral ischemia/reperfusion injury, 2, 3, 5-triphenyl-tetrazolium chloride (TTC) staining, dUTP nick-end labeling (TUNEL) assay, and Cytochrome C (Cyt C) release were performed in MCAO rats. The results support that GA is useful against cerebral ischemia/reperfusion injury as a potential protective agent.

[Effects of aquatic plants during their decay and decomposition on water quality].

Taking 6 aquatic plant species as test objects, a 64-day decomposition experiment was conducted to study the temporal variation patterns of nutrient concentration in water body during the process of the aquatic plant decomposition. There existed greater differences in the decomposition rates between the 6 species. Floating-leaved plants had the highest decomposition rate, followed by submerged plants, and emerged plants. The effects of the aquatic plant species during their decomposition on water quality differed, which was related to the plant biomass density. During the decomposition of Phragmites australis, water body had the lowest concentrations of chemical oxygen demand, total nitrogen, and total phosphorus. In the late decomposition period of Zizania latifolia, the concentrations of water body chemical oxygen demand and total nitrogen increased, resulting in the deterioration of water quality. In the decomposition processes of Nymphoides peltatum and Nelumbo nucifera, the concentrations of water body chemical oxygen demand and total nitrogen were higher than those during the decomposition of other test plants. In contrast, during the decomposition of Potamogeton crispus and Myriophyllum verticillatum, water body had the highest concentrations of ammonium, nitrate, and total phosphorus. For a given plant species, the main water quality indices had the similar variation trends under different biomass densities. It was suggested that the existence of moderate plant residues could effectively promote the nitrogen and phosphorus cycles in water body, reduce its nitrate concentration to some extent, and decrease the water body nitrogen load.

A dinucleotide motif in oligonucleotides shows potent immunomodulatory activity and overrides species-specific recognition observed with CpG motif.

Bacterial and synthetic DNAs containing CpG dinucleotides in specific sequence contexts activate the vertebrate immune system through Toll-like receptor 9 (TLR9). In the present study, we used a synthetic nucleoside with a bicyclic heterobase [1-(2'-deoxy-beta-d-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine; R] to replace the C in CpG, resulting in an RpG dinucleotide. The RpG dinucleotide was incorporated in mouse- and human-specific motifs in oligodeoxynucleotides (oligos) and 3'-3-linked oligos, referred to as immunomers. Oligos containing the RpG motif induced cytokine secretion in mouse spleen-cell cultures. Immunomers containing RpG dinucleotides showed activity in transfected-HEK293 cells stably expressing mouse TLR9, suggesting direct involvement of TLR9 in the recognition of RpG motif. In J774 macrophages, RpG motifs activated NF-kappa B and mitogen-activated protein kinase pathways. Immunomers containing the RpG dinucleotide induced high levels of IL-12 and IFN-gamma, but lower IL-6 in time- and concentration-dependent fashion in mouse spleen-cell cultures costimulated with IL-2. Importantly, immunomers containing GTRGTT and GARGTT motifs were recognized to a similar extent by both mouse and human immune systems. Additionally, both mouse- and human-specific RpG immunomers potently stimulated proliferation of peripheral blood mononuclear cells obtained from diverse vertebrate species, including monkey, pig, horse, sheep, goat, rat, and chicken. An immunomer containing GTRGTT motif prevented conalbumin-induced and ragweed allergen-induced allergic inflammation in mice. We show that a synthetic bicyclic nucleotide is recognized in the C position of a CpG dinucleotide by immune cells from diverse vertebrate species without bias for flanking sequences, suggesting a divergent nucleotide motif recognition pattern of TLR9.