Objective To investigate the impact of cardiomyocyte ferroptosis on acute myocardial infarction(AMI)and its relationship with the expression of long non-coding RNA(lncRNA)GAS5.Methods An AMI model was established in eighteen male SD rats(6-8 weeks old),and then the subjected rats were randomly divided into blank control group,sham operation group,and model group,6 animals in each group.In 2 weeks after surgery,echocardiography was used to evaluate heart function,and TTC staining,HE staining and TUNEL staining were employed re-spectively to observe myocardial infarct area,histopathological changes of myocardial tissues and apoptosis in cardiomyocytes.Serum Fe2+concentration was measured with an iron ion detection kit.The expression levels of lncRNA GAS5,nuclear factor erythroid-derived 2-like 2(Nrf2),and glutathione peroxidase 4(GPX4)in myocardial tissues were detected with QT-PCR.Linear corre-lation analysis was performed to investigate the relationship between the expression of lncRNA GAS5,Nrf2 and GPX4 with Fe2+concentration.Western blotting was conducted for the protein levels of ferroptosis-related proteins,glutathione peroxidase 4(GPX4),nuclear factor erythroid-derived 2-like 2(Nrf2),glucose-regulated protein 78(GRP78),and cysteinyl aspartate specific proteinase 12(Caspase-12)in myocardial tissues.Results Western blotting revealed obvious in-creases in the protein levels of ferroptosis related proteins GRP78(1.11±0.13 vs 0.51±0.08,P＜0.01)and Caspase-12(1.23±0.05 vs 0.92±0.07,P＜0.05)and a decrease in those of ferroptosis inhibitor GPX4(0.27±0.11 vs 0.68±0.10,P＜0.01)and Nrf2(0.30±0.12 vs 0.58±0.04,P＜0.05)in the model group than the sham operation group.Additionally,QT-PCR showed that the mRNA levels of GPX4 and Nrf2 were notably lower,indicating cardiomyocyte ferroptosis,while that of lncRNA GAS5 was remarkably higher in the myocardial tissues of the model group than the sham operation group(P＜0.01).What's more,the expression of lncRNA GAS5 had a positive correlation with serum Fe2+concentration(P＜0.05).Conclusion AMI is closely associated with cardiomyocyte ferroptosis.lncRNA GAS5 is involved in the regulation of ferroptosis by Nrf2/GPX4 signaling pathway,which thus mediating the occurrence of heart failure after AMI.

The cross regional loose medical alliance is an important carrier in the current integrated development process of medical services in the Yangtze River Delta region. Smith policy implementation process model was used to analyze the development difficulties of cross regional loose medical alliances from idealized policies, policy implementation institutions, policy target groups, and policy implementation environment. Such medical alliances were formed under the background of integrated development in the Yangtze River Delta, with Shanghai′s tertiary public hospitals as leading units and medical institutions in Jiangsu, Zhejiang, and Anhui provinces as member units. Analysis showed that the policies for such medical alliances development had not yet clearly defined the organizational management mode, operational mechanism, and implementation path, and the corporate governance structure of medical alliance was immature; The policy implementation agencies were relatively lagging behind in the support of special funds and the formulation of related supporting policies; Participation of policy target groups was insufficient and their incentive mechanisms was imperfect; There were problems in the policy implementation environment, namely inconsistent medical and health service regulations and systems in different regions, different health financing capabilities of local governments, insufficient coordination of medical institution management concepts, and a lack of unified standards in information systems. Based on the above difficulties, this study proposed to strengthen the development planning and layout of cross regional loose medical alliances, and improve the corporate governance structure; To strengthen the government′s main responsibility and improving policy implementation capabilities; To improve the internal cooperation and operation mechanism of cross regional loose medical alliances, and enhance the sense of identity of the target group; To optimize the policy implementation environment and implement various support measures, so as to provide references for further promoting the coordinated development of high-quality medical resources in the Yangtze River Delta region.

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
China ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Humans ; Mutation ; Poly T ; RNA, Messenger/genetics*

Objective To compare the dosimetric characteristics of the methods of volumetric modulated arc therapy ( VMAT ) for craniospinal irradiation , and to compare their robustness to the field placement error . Methods Six patients receiving craniospinal irradiation were included. VMAT plans of each patient were optimized with overlap method and gradient-optimization method respectively using Pinnacle 9.8 VMAT treatment planning system. The length of the overlap region was set as 3 and 9 cm, respectively. Then the dose distributions under different VMAT programs were measured. Moreover, a 3 mm placement error was introduced, and the dose cold spot in the field junction region obtained by each plan was compared for robustness analysis. Results Under different overlapping lengths, the overlap method and the gradient optimization method both can optimize the VMAT plan that meeting the clinical requirements. In the field junction region, the dose distribution obtained by the overlap method was more uniform, and the difference in the uniformity index was statistically significant. When introducing a 3 mm placement error, the gradient optimization method obtained the most robust VMAT plan at 9 cm overlap length, and the overlap method could not obtained stabilized robust plan. Conclusions For the optimization of craniospinal irradiation VMAT plan, the commonly used overlap method can obtain a better dose distribution, but it can't improve robustness by increasing overlap length. However, using the gradient optimization method, the dose homogeneity in the field junction region is not good as the overlap method, but the plan robustness can be improved by increasing the overlap length.

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

Objective To investigate the supernatant of umbilical cord-derived mesenchymal stem cells (UCMSCs) on tumor necrosis factor-α(TNF-α) and apoptosis protein caspase-3 in diabetic rats model with skin ulcer. Methods 45 Sprague-Dawley rats were randomly divided into control group (acute wounds group), phosphate buffered saline (PBS) group and UCMSCs supernatant group. The diabetic rat model was constructed by injecting with alloxan by tail vein and feeding with high-fat diet. Diabetic skin ulcer (DSU) rat model was constructed by scratching a wound and infusing suspension of Staphylococcus aureus. In the control group, the diabetic rats (n=15) were scratched to form a wound and treated by tail vein injection of 100μl PBS. In the PBS group, DSU rats (n=15) were treated by tail vein injection of 100μl PBS, and then 100μl PBS was dropped at the ulcer site. In the UCMSCs supernatant group, freeze-dried powder of UCMSCs supernatant was dissolved in 200μl PBS, 100μl of which was injected into the tail vein of DSU rats (n=15), and other 100μl was dropped at the ulcer site. After 5 days of the treatments, the levels of serum TNF-αwere detected by radioimmunoassay method, and the expression of TNF-αand caspase-3 in the ulcer tissues of rats was detected by polymerase chain reaction and Western Blot. Results The levels of TNF-αin the PBS group [(35.9±3.7)μg/L] were significantly higher than that of the control group [(11.4±4.9)μg/L] and the UCMSCs group [(14.7±6.6)μg/L] (all P<0.05). The levels of mRNA and protein expression of TNF-αand caspase-3 in the UCMSCs group were significantly lower than those of the PBS group (all P<0.05), and have no significant differences with respect to those of the control group (all P>0.05). Conclusions UCMSCs supernatant treatments can effectively down-regulate the expression of TNF-αand caspase-3 in ulcer tissue of DSU rats, and play an anti-inflammatory and anti-apoptotic effect.

Objective To investigate the clinical efficacy of Telmisartan combined with Atorvastatin in treating patients with idiopathic paroxysmal atrial fibrillation(IPAF).Methods 70 cases of IPAF were randomly divided into study group(given treatment of Telmisartan combined with Atorvastatin)and control group(given treatment of Telmisartan),35 cases in each group,all patients got 2 years follow-up visit.The change of CRP and the arrhythmia recurrence were observed after treatment.Results After surgery,patients were better than before,but the efficiency in study group was significantly higher than control group(88.6％ vs 68.6％,P ＜0.05);CRP of the two groups were significantly reduced after treatment,two groups have significant difference(P ＜ 0.05).Conclusion Curative effect of atorvastatin combined with telmisartan on IPAF is better than that of telmisartan treatment and clinical implementation should be promoted.

ObjectiveTo evaluate the diagnostic value of ultrasound or CT guided percutaneous Trucut needle biopsy on the diagnosis of pancreatic tumors.Methods One hundred and twenty-four patients clinically diagnosed as pancreatic cancer without pathological diagnosis underwent percutaneous pancreatic biopsy by using Trucut needle under ultrasound or CT guidance.ResultsOne hundred and nine procedures of ultrasound-guided biopsy and 15 procedures of CT-guided biopsy were performed,and one patient received 2.3times of punctures.Tissue samples were obtained in all 124 patients,the diagnostic accuracy was 95.2％,among them 115 were adenocarcinoma,5 were cystadenoma,2 were metastasis cancer,1 was cancer of unknown origin and 1 was normal.The sensitivity,specificity,and accuracy were 99.2％ 100％,and 99.2％,respectively.Transient serum amylase increase was observed in 3 patients; 5 patients' abdominal pain aggravated,but all recovered with conservative management.One patient was found to have tumor seeding on the spot of insertion after 34 days.No other major complications occurred.ConclusionsUltrasound or CTguided percutaneous pancreatic 16 ～ 18G Trucut needle biopsy is a safe and simple procedure with excellent diagnostic value for pancreatic cancer.

Vacuum pyrolysis of phenolic resin laminate substrate in temperature-programmed furnace reactor was studied.The sample and product oils were characterized by elemental analysis, Fourier transform infrared (FT-IR) analysis and gas chromatography-mass spectrometry(GC-MS).Analytical results showed that the up per clear liquid of pyrolysis oils was mainly consisted of water-soluble substances, such as phenol, cresol, xy lenol, sugars, hydantoins, morpholines, pyranones and pyridine derivatives compounds, etc., while the lower sediment was mainly insoluble or hardly water-soluble substances, such as the big substituent phenolics (the number of substituent carbon atoms of which is greater than or equal to 2), aryl phosphate esters, fatty acid esters and nitrile compounds, and so on.Both of the upper clear liquid and lower sediment have a higher content of melamines.

Objective To evaluate the influence of respiration on the radiation dose distribution within target volume in radiotherapy with film dosimetry. Methods Radiation of 50 MU was delivered by a square, round, ellipse, dumb bell, or female shaped filed to the films within a moving or motionless Respiration Motion Phantom respectively, the dose distributions for the two motion status were measured and compared. In order to further verify the impact of respiration, a plank phantom was used on different shifting value: 0, 0.5, 1.0, 1.5 and 2.0 cm, respectively. A square, round, or eUipse-shaped filed was used for irradiation and the distributions in different status were measured and compared with film dosimetry. Iso-dose line comparison, NAT(Normalized Agreement Tests) and γ comparison were used for the comparison of dose distributions. Fs can be an index to reflect the variability of the areas that surrounded by iso-dose lines. (FS90, FS50, FS25 delegates the ratio of the areas that surrounded by 90 %,50 %,25 % iso-dose hne in different situation respectively). Results (1) Compared with motionless situation, the FS90 in horizontal movement situation became small and the FS25 became large. As the displacement became larger, the FS90 became larger and the FS25 became smaller. FS in vertical movement situation, square and dumb bell fields changed while the others didn't have a change. (2)γ and NAT comparison: In the horizontal movement situation, compared with the static phantom, Pγ < 60 % and PNAT < 75 %. Under vertical movement situation, Pγ were less than 85 % for the square, round, dumb bell and female shaped fileds. In the plank phantom verification, Pγ and PNAT became smaller as the movement became larger. Conclusions The respiration can impact on the dose distribution within the target volume in radiotherapy, leading to a smaller area of higher dose level and an expanded area of lower dose level. The influence will become more significant with larger movement of the target.