Effect of combined vitamin D and microwave ablation of parathyroid glands on blood pressure and cardiac function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism

Purpose: To investigate the effect of microwave ablation of parathyroid glands in combination with active vitamin D on blood pressure and cardiac function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism. Methods: One hundred and twenty maintenance-hemodialysis patients with uremic secondary hyperparathyroidism admitted to Meizhou People’s Hospital were assigned to 2 groups (A and B) in the order of their admission. Each group had 60 patients. Both groups were treated with active vitamin D, while patients in group A were, in addition, subjected to microwave ablation of parathyroid glands. Blood pressure, and indices for cardiac function, thyroid function s and anemia were determined. Results: After treatment, the blood pressure of group A was significantly lower than that of group B (p < 0.05). Moreover, after treatment, there were significant improvements in indices of cardiac function, thyroid function and anemia in group A patients, relative to group B patients. Conclusion: Microwave ablation of parathyroid glands, when combined with active vitamin D, improves blood pressure, cardiac function and anemia status. Furthermore, the combined therapy enhances recovery of thyroid function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism. However, the combined therapy should be subjected to further clinical trials prior to application in clinical practice. Keywords: Microwave ablation; Parathyroid glands; Active vitamin D; Hyperparathyroidis

Impact of the National Reimbursement Drug List Negotiation Policy on Accessibility of Anticancer Drugs in China: An Interrupted Time Series Study

Objective: Since 2016, the Chinese government has been regularly implementing the National Reimbursement Drug List Negotiation (NRDLN) to improve the accessibility of drugs. In the second round of NRDLN in July 2017, 18 anticancer drugs were included. This study analyzed the impact of the NRDLN on the accessibility of these 18 anticancer drugs in China. Methods: National hospital procurement data were collected from 2015 to 2019. As measurements of drug accessibility, monthly average of drug availability or defined daily dose cost (DDDc) was calculated. Interrupted time series (ITS) analysis was employed to evaluate the impact of NRDLN on drug accessibility. Multilevel growth curve models were estimated for different drug categories, regions or levels of hospitals. Results: The overall availability of 18 anticancer drugs increased from about 10.5% in 2015 to slightly over 30% in 2019. The average DDDc dropped from 527.93 CNY in 2015 to 401.87 CNY in 2019, with a reduction of 23.88%. The implementation of NRDLN was associated with higher availability and lower costs for all 18 anticancer drugs. We found an increasing level in monthly drug availability (β2 = 2.1126), which ascended more sharply after the implementation of NRDLN (β3 = 0.3656). There was a decreasing level in DDDc before July 2017 (β2 = −108.7213), together with a significant decline in the slope associated with the implementation of NRDLN (β3 = −4.8332). Compared to Traditional Chinese Medicines, the availability of Western Medicines was higher and increased at a higher rate (β3 = 0.4165 vs. 0.1108). Drug availability experienced a larger instant and slope increase in western China compared to other regions, and in secondary hospitals than tertiary hospitals. Nevertheless, regional and hospital-level difference in the effect of NRDLN on DDDc were less evident. Conclusion: The implementation of NRDLN improves the availability and reduces the cost of some anticancer drugs in China. It contributes to promoting accessibility of anticancer drugs, as well as relieving regional or hospital-level disparities. However, there are still challenges to benefit more patients sufficiently and equally. It requires more policy efforts and collaborative policy combination

An atypical GdpP enzyme linking cyclic nucleotide metabolism to osmotic tolerance and gene regulation in Mycoplasma bovis

Nucleotide second messengers play an important role in bacterial adaptation to environmental changes. Recent evidence suggests that some of these regulatory molecular pathways were conserved upon the degenerative evolution of the wall-less mycoplasmas. We have recently reported the occurrence of a phosphodiesterase (PDE) in the ruminant pathogen Mycoplasma bovis, which was involved in c-di-AMP metabolism. In the present study, we demonstrate that the genome of this mycoplasma species encodes a PDE of the GdpP family with atypical DHH domains. Characterization of M. bovis GdpP (MbovGdpP) revealed a multifunctional PDE with unusual nanoRNase and single-stranded DNase activities. The alarmone ppGpp was found unable to inhibit c-di-NMP degradation by MbovGdpP but efficiently blocked its nanoRNase activity. Remarkably, MbovGdpP was found critical for the osmotic tolerance of M. bovis under K+ and Na+ conditions. Transcriptomic analyses further revealed the biological importance of MbovGdpP in tRNA biosynthesis, pyruvate metabolism, and several steps in genetic information processing. This study is an important step in understanding the role of PDE and nucleotide second messengers in the biology of a minimal bacterial pathogen

Early transient suppression of immune checkpoint proteins T-cell immunoglobulin mucin-3 and programmed cell death-1 in peripheral blood lymphocytes after blastocyst transfer is associated with successful implantation

Objective To compare the changing peripheral levels of immune checkpoint proteins T-cell immunoglobulin mucin-3 (Tim-3)/galectin-9 (Gal-9), and programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) over a 9-day period after blastocyst transfer between women who did and did not conceive. Design Prospective observational study. Setting University teaching hospital. Patients(s) Fifty-one infertile women undergoing day-5 blastocyst transfer. Intervention(s) Serial blood samples obtained on the day of embryo transfer (ET), and 3, 6, and 9 days afterward for measurement of membranous Tim-3 and PD-1 expression on various peripheral lymphocytes by flow cytometry, and serum concentrations of ligands Gal-9 and PD-L1 by ELISA. Main Outcome Measure(s) Membranous Tim-3 and PD-1 expression on lymphocytes and serum Gal-9 and PD-L1 concentrations and comparison of results between pregnant and nonpregnant women. Result(s) In women who conceived, the measurements exhibited three different types of response: [1] a transient and statistically significant reduction of Tim-3+NK-like T cells, Tim-3+/PD-1+CD8+ T cells, and Tim-3+/PD-1+CD4+ T cells that returned back to baseline level 9 days after ET; [2] a reduction followed by steady increase to above baseline level on day 9 (Tim-3+CD56dimNK cells); [3] a steady increase in expression after ET to reach a level statistically significantly higher than that of the baseline by day 9 (Tim-3+CD56brightNK cells). Women who did not conceive showed no statistically significant fluctuation in any of the parameters measured across the four time pointswith exception of increased Tim-3 expression on NK cells on day 9. Conclusion(s) Successful blastocyst implantation is associated with a reduction of Tim-3 and PD-1 expression in peripheral lymphocytes on days 3 and 6 that is no longer apparent on day 9

Hierarchical Clustering and Similarity Statistics for Solving and Investigating Cell Formation Problems

In cellular manufacturing, cell formation (CF) is to group similar machines into manufacturing cells and parts to product families. This research focuses on advancing hierarchical clustering to solve CF problems and analyzing similarity statistics to investigate CF problems. In the first aspect, the purpose is to find high-quality solutions for CF problems considering production information. Two-mode similarity coefficient is applied to simultaneously form machine groups and part families based on the classical framework of hierarchical clustering. The proposed simultaneous clustering algorithm has been tested through some literature examples. The results demonstrate that the proposed method can at least yield solutions comparable to the solutions obtained by metaheuristics. In the second aspect, the purpose is to distinguish whether a CF problem is difficult or not so that the users can decide whether using economical heuristics or relatively demanding metaheuristics for problem solving. Histograms are used to report the distribution of similarity values. The histogram of a not-difficult problem often presents a U-shape. To further quantify this observation, proxy measure from the Kolmogorov-Smirnov test is used to examine how well the distribution of similarity values fits the normal distribution which the similarity values of a difficult CF problem tend to show. By judging whether the proxy measure is high or low, the difficulty of a given CF problem can be determined. Sixty random matrices are used to examine the statistical approach, and the analysis results are verified by using simultaneous clustering method and genetic algorithm to solve these matrices. The results indicate that the proposed method can discern the difficulty of CF problems so that the users can select proper solutions approaches

Similarity Statistics for Clusterability Analysis with the Application of Cell Formation Problem

This paper proposes the use of the statistics of similarity values to evaluate the clusterability or structuredness associated with a cell formation (CF) problem. Typically, the structuredness of a CF solution cannot be known until the CF problem is solved. In this context, this paper investigates the similarity statistics of machine pairs to estimate the potential structuredness of a given CF problem without solving it. One key observation is that a well-structured CF solution matrix has a relatively high percentage of high-similarity machine pairs. Then, histograms are used as a statistical tool to study the statistical distributions of similarity values. This study leads to the development of the U-shape criteria and the criterion based on the Kolmogorov-Smirnov test. Accordingly, a procedure is developed to classify whether an input CF problem can potentially lead to a well-structured or ill-structured CF matrix. In the numerical study, 20 matrices were initially used to determine the threshold values of the criteria, and 40 additional matrices were used to verify the results. Further, these matrix examples show that genetic algorithm cannot effectively improve the well-structured CF solutions (of high grouping efficacy values) that are obtained by hierarchical clustering (as one type of heuristics). This result supports the relevance of similarity statistics to preexamine an input CF problem instance and suggest a proper solution approach for problem solving.Peer Reviewe

Simultaneous Hierarchical Clustering for Cell Formation Problems with Production Information

The purpose of this paper is to advance the similarity coefficient method to solve cell formation (CF) problems in two aspects. Firstly, while numerous similarity coefficients have been proposed to incorporate different production factors in literature, a weighted sum formulation is applied to aggregate them into a nonbinary matrix to indicate the dependency strength among machines and parts. This practice allows flexible incorporation of multiple production factors in the resolution of CF problems. Secondly, a two-mode similarity coefficient is applied to simultaneously form machine groups and part families based on the classical framework of hierarchical clustering. This practice not only eliminates the sequential process of grouping machines (or parts) first and then assigning parts (or machines), but also improves the quality of solutions. The proposed clustering method has been tested through twelve literature examples. The results demonstrate that the proposed method can at least yield solutions comparable to the solutions obtained by metaheuristics. It can yield better results in some instances, as well