Evaluation of a pilot cooperative medical scheme in rural China: impact on gender patterns of health care utilization and prescription practices

<p>Abstract</p> <p>Background</p> <p>In 2003 the Chinese government introduced voluntary cooperative medical schemes (CMS), soon to be in place throughout rural China. Families who chose to enroll do so as a single unit and nothing is known about any differential effect of these new schemes on family members. This study evaluates the impact of one pilot CMS in Anhui Province on health care use by girls aged less than 5 years and women 65 years or older, and on the pattern and cost of prescriptions.</p> <p>Methods</p> <p>Health care records were extracted covering a 10 year period, before, during and after the pilot CMS in 4 townships, one with the intervention and 3 comparison townships without. The impact of the intervention on the age and gender distribution of patients presenting for health care and on the prescription of certain drugs was assessed by logistic regression. The cost of prescriptions before, during and after the intervention period was also assessed.</p> <p>Results</p> <p>203,058 registration and 643,588 prescription records were identified. During the intervention there was a reduced likelihood overall that a patient was female (OR = 0.92: 95%CI 0.87 - 0.97) at the intervention site. Girls aged < 5 years had an increased likelihood of health care (OR = 1.41: 95%CI 1.23 - 1.59) during the CMS, but women ≥ 65 years were relatively disadvantaged (OR = 0.84: 95%CI 0.75 - 0.95). The use of antibiotics and systemic steroids increased disproportionately at the intervention site for patients ≥ 5 years. Prescription costs at the township hospital also increased at the intervention site, particularly for older men.</p> <p>Conclusions</p> <p>This evaluation suggests that all family members did not benefit equally from the pilot CMS and that women ≥ 65 years may be disadvantaged by the newly available reimbursements of health care costs through the CMS. It points to the need, in future evaluations, to use individuals rather than families as the unit of analysis, in order to determine whether such health care inequalities are wide-spread and persistent or are reduced in the longer term. The results also support earlier concerns about the influence of new funding resources on prescription practices and the need for regulation of for-profit prescribing.</p

The genome of hibiscus hamabo reveals its adaptation to saline and waterlogged habitat

Hibiscus hamabo is a semi-mangrove species with strong tolerance to salt and waterlogging stress. However, the molecular basis and mechanisms that underlie this strong adaptability to harsh environments remain poorly understood. Here, we assembled a high-quality, chromosome-level genome of this semi-mangrove plant and analyzed its transcriptome under different stress treatments to reveal regulatory responses and mechanisms. Our analyses suggested that H. hamabo has undergone two recent successive polyploidy events, a whole-genome duplication followed by a whole-genome triplication, resulting in an unusually large gene number (107 309 genes). Comparison of the H. hamabo genome with that of its close relative Hibiscus cannabinus, which has not experienced a recent WGT, indicated that genes associated with high stress resistance have been preferentially preserved in the H. hamabo genome, suggesting an underlying association between polyploidy and stronger stress resistance. Transcriptomic data indicated that genes in the roots and leaves responded differently to stress. In roots, genes that regulate ion channels involved in biosynthetic and metabolic processes responded quickly to adjust the ion concentration and provide metabolic products to protect root cells, whereas no such rapid response was observed from genes in leaves. Using co-expression networks, potential stress resistance genes were identified for use in future functional investigations. The genome sequence, along with several transcriptome datasets, provide insights into genome evolution and the mechanism of salt and waterlogging tolerance in H. hamabo, suggesting the importance of polyploidization for environmental adaptation.DATA AVAILABILITY: The data supporting the findings of this work are available within the paper and its Supporting Information files. The data sets generated and analyzed during this study are available from the corresponding author upon request. All the whole-genome raw data generated during this study have been deposited in the SRA database under BioProject number PRJNA759075. Transcriptome clean data have been deposited in the SRA database under BioProject number PRJNA759717. The final chromosome-scale genome assembly and annotation data have been deposited in the Figshare database (https://doi.org/10.6084/m9.figshare.19142558.v1).Six Talent Peaks Project of Jiangsu Province (NY-042); Open Fund of the Jiangsu Key Laboratory for the Research and Utilization of Plant Resources (JSPKLB201928); Talent Training Funds of the Institute of Botany, Jiangsu Province and Chinese Academy of Sciences.https://academic.oup.com/hrBiochemistryGeneticsMicrobiology and Plant Patholog

Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling

Multi-Patterned Dynamics of Mitochondrial Fission and Fusion in a Living Cell

Mitochondria are highly-dynamic organelles, but it is challenging to monitor quantitatively their dynamics in a living cell. Here we developed a novel approach to determine the global occurrence of mitochondrial fission and fusion events in living human epithelial cells (Hela) and mouse embryonic fibroblast cells (MEF). Distinct patterns of sequential events including fusion followed by fission (Fu-Fi), the so-called “kiss and run” model previously described, fission followed by fusion (Fi-Fu), fusion followed by fusion (Fu-Fu), and fission followed by fission (Fi-Fi) were observed concurrently. The paired events appeared in high frequencies with short lifetimes and large sizes of individual mitochondria, as compared to those for unpaired events. The high frequencies of paired events were found to be biologically significant. The presence of membrane uncoupler CCCP enhanced the frequency of paired events (from both Fu-Fi and Fi-Fu patterns) with a reduced mitochondrial size. Knock-out of mitofusin protein Mfn1 increased the frequency of fission with increased lifetime of unpaired events whereas deletion of both Mfn1 and Mfn2 resulted in an instable dynamics. These results indicated that the paired events were dominant but unpaired events were not negligible, which provided a new insight into mitochondrial dynamics. In addition to kiss and run model of action, our data suggest that, from a global visualization over an entire cell, multiple patterns of action appeared in mitochondrial fusion and fission

Ets-1 Targeted by MicroRNA-221 Regulates Angiotensin II-Induced Renal Fibroblast Activation and Fibrosis

Background: Fibroblast activation is one of the most important mechanisms for Angiotensin II (Ang II) in promoting renal fibrosis. Transcription factor Ets-1 is recognized to play a key role in kidney diseases. However, the role and mechanisms of Ets-1 in Ang-II induced fibroblast activation and kidney fibrosis are not fully understood. Methods: Mice were treated with Ang II via osmotic mini-pumps or Ang II expression plasmid (pAng II). Cultured normal rat kidney interstitial fibroblast (NRK-49F) cells were incubated with Ang II. Role of Ets-1 in renal fibrosis and fibroblast activation were assessed by Western blot, Immunohistochemical staining‚MTT, Boyden chamber and Immunofluorescence staining. Effects of miR-221 on Ets-1 and fibroblast activation were investigated by MTT, Boyden chamber, Western blot and Q-PCR. Results: We found that Ets-1 was up-regulated in fibrotic kidneys. Similarly, Ang II could activate NRK-49F cells as demonstrated by up-regulated α-SMA and fibronectin(FN) expression and enhanced cell proliferation and migration. Ang II also induced Ets-1 expression in NRK-49F cells in a dose and time dependent manner. Knock-down of Ets-1 by RNA interference attenuated Ang II-induced activation of NRK-49F cells. Ets-1 was previously reported as a target of microRNA-221 (miR-221). In Ang II-induced fibrotic kidney, miR-221 was down-regulated. Similar results were observed in Ang II treated NRK-49F cells. Ectopic expression of miR-221 mimic attenuated the up-regulation of Ets-1 by Ang II in NRK-49F cells, which further prevented the activation of NRK-49F cells. However, the inhibitor of miR-221 aggravated Ang II induced Ets-1 expression and NRK-49F cells activation. Conclusions: Our study suggests that miR-221/Ets-1 axis takes an important role in mediating AngII induced interstitial fibroblast activation and renal fibrosis

Calmodulin-dependent Protein Kinase II/cAMP Response Element-binding Protein/Wnt/β-Catenin Signaling Cascade Regulates Angiotensin II-induced Podocyte Injury and Albuminuria

Close view of the attic story; A commission that involved Borromini as an architect of both churches and palazzi was the Collegio di Propaganda Fide, the headquarters of the Catholic missionary congregation. Although he took charge of building work in 1646, his greatest contributions to shaping the palazzo belong to his last creative years. The complex includes a dormitory and chapel as well. The College was founded by Urbanus VIII for the training of missionaries. The palace is still devoted to its original purpose, but the ground floor has been converted to shopping. The facade over the Piazza di Spagna is by Bernini, whereas Borromini designed the convex and concave entrance facade facing Via Propaganda. Source: Grove Art Online; http://www.groveart.com/ (accessed 12/2/2007

Autophagy Attenuates Diabetic Glomerular Damage through Protection of Hyperglycemia-Induced Podocyte Injury

<div><p>Despite the recent attention focused on the important role of autophagy in maintaining podocyte homeostasis, little is known about the changes and mechanisms of autophagy in podocyte dysfunction under diabetic condition. In this study, we investigated the role of autophagy in podocyte biology and its involvement in the pathogenesis of diabetic nephropathy. Podocytes had a high basal level of autophagy. And basal autophagy inhibition either by 3-methyladenenine (3-MA) or by Beclin-1 siRNA was detrimental to its architectural structure. However, under diabetic condition in vivo and under high glucose conditions in vitro, high basal level of autophagy in podocytes became defective and defective autophagy facilitated the podocyte injury. Since the dynamics of endoplasmic reticulum(ER) seemed to play a vital role in regulating the autophagic flux, the results that Salubrinal/Tauroursodeoxycholic acid (TUDCA) could restore defective autophagy further indicated that the evolution of autophagy may be mediated by the changes of cytoprotective output in the ER stress. Finally, we demonstrated in vivo that the autophagy of podocyte was inhibited under diabetic status and TUDCA could improve defective autophagy. Taken together, these data suggested that autophagy might be interrupted due to the failure of ER cytoprotective capacity upon high glucose induced unmitigated stress, and the defective autophagy might accelerate the irreparable progression of diabetic nephropathy.</p> </div

Circulating MiR-133a as a biomarker predicts cardiac hypertrophy in chronic hemodialysis patients.

BACKGROUND: MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form and have emerged as potential diagnostic markers in patients with cardiovascular disease. Our study aimed to assess circulating miR-133a levels in MHD patients and the relation of miR-133a to cardiac hypertrophy. METHODS: We profiled miRNAs using RNA isolated from the plasma of participants. The results were validated in 64 MHD patients and 18 healthy controls. RESULTS: Levels of plasma miR-133a decreased in MHD patients with LVH compared with those in healthy controls. Plasma miR-133a concentrations were negatively correlated with LVMI and IVS. After single hemodialytic treatment, plasma miR-133a levels remained unchanged. Cardiac Troponin I and T were not associated with LVMI and IVS. CONCLUSIONS: Our observations supplied the possibility that circulating miR-133a could be a surrogate biomarker of cardiac hypertrophy in MHD patients

Uric acid induces RANTES, MCP-1 and TNF-α expression in hyperuricemia mice kidneys.

<p>(a) Q-PCR results showed that renal RANTES, MCP-1 and TNF-α mRNA expression were increased in kidney of hyperuricemia mice after continuous injection of uric acid for 7d and 14d, respectively. *<i>P</i><0.05 versus sham-control. (b) Western blot results showed that renal RANTES protein expression was increased in hyperuricemia mice kidneys. (c) Graphic presentation of relative RANTES protein abundance normalized to actin. *<i>P</i><0.05 versus control (<i>n</i> = 5).</p

TUDCA attenuates albuminuria and improves histopathological lesion in diabetic mice.

<p>(A) TUDCA attenuates albuminuria in diabetic mice. Shown is graphic presentation of urinary albumin/creatinine ratio. Data are presented as means ± SEM of three experiments. n = 6; <i>* P</i><0.05 vs. normal control. # <i>P</i><0.05 vs. the group of 28 day diabetic mouse. (B) Representative SDS-PAGE shows the urine proteins in different groups of mice as indicated. Numbers (1 and 2) denote each individual animal in a given group. (C–K) The light microscopic appearance of representative glomeruli (400× magnification) is shown stained with H&E (C–E), PAS (F–H), and Masson's trichrome (I–K). The left column (C, F and I): control group; The second column (D, G and J): diabetic group; The third column (E, H and K): diabetic group treated with 500 mg/kg/day TUDCA. (L): Quantification of extracellular mesangial matrix area in relation to glomerular tuft area. Results are expressed as average percentage of glomerular area occupied by the mesangial matrix. 30 glomeruli were evaluated for each experimental animal (n = 6) through the middle part of the kidney. <i>* P</i><0.05 vs. normal control. # <i>P</i><0.05 vs. the group of 28 day diabetic mouse.</p