Policy analysis in the field of rare diseases in China: a combined study of content analysis and Bibliometrics analysis.

Introduction: The Chinese government has made significant strides in addressing the needs of individuals affected by rare diseases in recent years. This paper aims to provide a comprehensive analysis of national rare disease policies in China from 2009 to 2022, using a mixed-methods approach. Methods: A two-dimensional analytical framework, which includes policy tools and policy themes, is introduced to analyze the rare disease policies comprehensively. Drawing on the policy tools theory proposed by Rothwell and Zegveld, this paper evaluates the tools used in rare disease policies. Co-word analyses and network analyses are employed to identify key themes in rare disease policies and collaboration among government departments. Results: The rare disease policy landscape in China is undergoing rapid growth, with an increasing number of government departments involved in policy formulation. However, further collaboration between departments is needed to strengthen these policies. Environment-based and supply-based tools are preferred in rare disease policies. The policy themes can be grouped into four categories: (1) Registration, Approval and Supply of Rare Disease Drugs, (2) Construction of Diagnosis and Treatment System for Rare Diseases, (3) Development and Genericization of Rare Disease Drugs, and (4) Social Security for Patients with Rare Diseases. Discussion: The study provides valuable insights into the current state of rare disease policies in China and offers suggestions for policy improvement. The results show that the Chinese government has made efforts to address the needs of individuals affected by rare diseases, but there is still room for improvement. The collaboration between government departments needs to be strengthened to achieve better rare disease policies. The findings of this study have implications for other countries with similar healthcare systems and can contribute to a better understanding of the impact of rare disease policies on public health.

Effects of Hypothermic Hypoxia/Reoxygenation Fibroblast Culture Medium Containing Sevoflurane on Cardiomyocytes.

We established a model of hypothermic hypoxia/reoxygenation injury of fibroblasts, simulated the process of ischemia/reperfusion injury during cardiopulmonary bypass, and studied the effects of cardiac fibroblasts on cardiomyocyte activity, connexin 43 (Cx43), and calmodulin kinase II (CaMKII) expression. Furthermore, the effects of sevoflurane-treated fibroblast culture medium on cardiac activity, Cx43 protein, and CaMKII expression were observed. The results showed that the fibroblast culture medium damaged by hypothermic hypoxia/reoxygenation could reduce the beating frequency of cardiomyocytes, increase the mortality of cardiomyocytes, decrease the relative expression of Cx43, and increase the relative expression of CaMKII. However, sevoflurane containing hypothermic hypoxia/reoxygenation injury fibroblast culture medium can increase the beating frequency of cardiomyocytes, reduce the mortality of cardiomyocytes, increase the relative expression of Cx43 protein, and decrease the relative expression of CaMKII. The results suggest that the antiarrhythmic effects of sevoflurane on the expression of Cx43 and CaMKII are related to fibroblasts.

Prolonged duration of repolarization and decreased conduction velocity in the atrial myocardium after hypothermic ischemia-reperfusion may be related to expressions of inward rectifier potassium channel 2.1 protein and connexin 40.

OBJECTIVES: The study aimed to determine the role of inward rectifier potassium channel 2.1 protein and connexin 40 expressions in regulating the duration of repolarization and conduction velocity of right atrial myocardium in rats following hypothermic ischemia-reperfusion. METHODS: The Langendorff isolated rat cardiac perfusion models were divided into control (C) and hypothermic ischemia-reperfusion groups, with 8 models in group C and 16 models in group ischemia-reperfusion. Depending on the incidence of atrial arrhythmia after reperfusion, the models in group ischemia-reperfusion were further divided into reperfusion non-atrial arrhythmia or reperfusion atrial arrhythmia subgroup. Right atrial monophasic action potential duration at 50% and 90% of repolarization after 30 minutes of continuous perfusion in group C and group ischemia-reperfusion (T0), 105 minutes of continuous perfusion in group C or after 15 minutes of reperfusion in group ischemia-reperfusion (T1) and 120 minutes of continuous perfusion in group C or 30 minutes of reperfusion in group ischemia-reperfusion (T2) were recorded. Right atrial conduction velocity and effective refractory period were recorded at T2. Then, the expressions of inward rectifier potassium channel 2.1 protein and connexin 40 in the right atrial myocardium were detected. RESULTS: Monophasic action potential duration at 50% and 90% were higher at T1 and T2 than those at T0 in subgroup reperfusion atrial arrhythmia (p < 0.05); monophasic action potential duration at 50% in subgroup reperfusion atrial arrhythmia were larger than group C and subgroup reperfusion non-atrial arrhythmia at T1 and T2 (p < 0.05); monophasic action potential duration at 90% in subgroup reperfusion atrial arrhythmia were larger than group C and subgroup reperfusion non-atrial arrhythmia at T1 and T2 (p < 0.05); effective refractory period in subgroup reperfusion atrial arrhythmia was greater than that in group C and subgroup reperfusion non-atrial arrhythmia, and the conduction velocity and the expressions of inward rectifier potassium channel 2.1 protein and connexin 40 were significantly lower than group C and subgroup reperfusion non-atrial arrhythmia (p < 0.05). CONCLUSIONS: The prolonged duration of repolarization and a decrease in conduction velocity of the atrial myocardium occur in rats after hypothermic ischemia-reperfusion. These observed effects may be related to the downregulated expressions of connexin 40 and inward rectifier potassium channel 2.1.

Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia-reperfusion arrhythmias.

BACKGROUND: Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, however, the effect of miRNAs on the progression of hypothermic ischemic-reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored. METHODS: Sprague-Dawley (SD) rats were randomly divided into two groups (n = 8): a normal control group (Group C) and a hypothermic ischemia-reperfusion group (Group IR), which were used to establish a Langendorff isolated cardiac perfusion model. According to the arrhythmia scoring system, rats in group IR were divided into a high-risk group (IR-H) and a low-risk group (IR-L). miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia-reperfusion and those of ventricular myocardium with hypothermic ischemia-RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia-RA were screened and verified. The target genes of these aberrantly expressed miRNAs were predicted using RNAhybrid and MiRanda software. Based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we determined the mRNA targets associated with these miRNAs and studied the miRNA-mRNA interaction during the cardiovascular disease progression. The aberrantly expressed miRNAs related to hypothermic ischemia-RA were validated by Real-time Quantitative polymerase chain reaction (RT-qPCR). RESULTS: Eight significantly aberrantly expressed miRNAs (rno-miR-122-5p, rno-miR-429, novel_miR-1, novel_miR-16, novel_miR-17, novel_miR-19, novel_miR-30, and novel_miR-43) were identified, among which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. The miRNA-mRNA interaction network graph showed that GJA1 gene was considered as the target of novel_miR-17. CONCLUSIONS: Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia-RA. Specific miRNAs, such as novel_miR-17 and rno-miR-429 are probably new potential targets for further functional studies of hypothermic ischemia-RA.

Ultra-Shallow Doping of GaAs with Mg, Cr, Mn and B Using Plasma Stimulated Room-Temperature Diffusion.

It is demonstrated that Mg, Cr, Mn and B can be doped close to GaAs surface by plasma doping without external bias at room temperature (RT). The process only takes a few minutes, and impurity densities in the range of 1018-1021/cm3 can be achieved with doping depths about twenty nanometers. The experiment results are analyzed and the physical mechanism is tentatively explained as follows: during the doping process, impurity ion implantation under plasma sheath voltage takes place, simultaneously, plasma stimulates RT diffusion of impurity atom, which plays the main role in the doping process. The enhanced RT diffusion coefficients of Mg, Cr, Mn and B in GaAs are all in the order of magnitude of 10-15 cm2sec-1. This is reported for the first time among all kinds of plasma assisted doping methods.

Effects of different concentrations of desflurane on the index of cardiac electrophysiological balance in gynecologic surgery patients.

The objectives were to observe the effects of different concentrations of desflurane on QT, QTc, Tp-e, Tp-e/QT, and the index of cardiac electrophysiological balance (iCEB). Sixty patients were randomly divided into group D1, group D2, and group D3 by using a random number table, 20 in each group. After entering the operating room, patients received 10 mL/kg hydroxyethyl starch, 0.1 mg/kg midazolam, 0.1 mg/kg vecuronium, 3 µg/kg fentanyl, and 0.3 mg/kg etomidate intravenously and then accepted intubation and mechanical ventilation. The desflurane evaporator was opened. The concentrations of desflurane in the D1, D2, and D3 groups were maintained at 0.6, 1.3, and 2.0 minimum alveolar concentration (MAC), respectively. Twelve-lead ECGs were recorded at time before induction (T1) and at 20 min after desflurane reached the required concentration (T2). HR and MAP were recorded measure and the QT interval, QTc interval, Tp-e interval, Tp-e/QT ratio, and iCEB were calculated. Compared with before inhalation (T1), the QTc interval was prolonged in the D1, D2, and D3 groups after inhalation of different concentrations of desflurane for 20 min (T2) (P < 0.05) and the Tp-e/QT ratio decreased in the D1 and D2 groups at T2 (P < 0.05). Compared with the D1 and D2 groups, the Tp-e/QT ratio of the D3 group increased at T2 (P < 0.05). There was no significant difference in Tp-e interval and iCEB at any time (P > 0.05). The study suggested that inhalation of desflurane at a normal concentration cannot cause arrhythmogenic characteristics and affect the cardiac electrophysiological stability.