Treatment of Diabetic Rats Mellitus-induced Erectile Dysfunction by Xiaoyaosan Based on Experiments / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of action and main active components of Xiaoyaosan in the treatment of diabetic mellitus-induced erectile dysfunction （DMED）. MethodStreptozotocin （STZ） was used to induce a diabetic rat model. The therapeutic efficacy of Xiaoyaosan was evaluated by measuring intracavernous pressure/mean arterial pressure （ICP/MAP） and using Masson's trichrome staining. The main active components， key targets， and potential signaling pathways of Xiaoyaosan for the treatment of DMED were predicted by network pharmacology and molecular docking. The predicted results were then validated by in vitro and in vivo experiments. ResultThe ICP/MAP measurements and Masson's staining results showed that compared with the results in the control group， the erectile function of rats in the model group was significantly reduced （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly reduced （P<0.01）. After treatment with Xiaoyaosan， compared with the results in the model group， the ICP/MAP value of the diabetic rats was significantly elevated （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly higher （P<0.01）. The results of network pharmacology showed that Xiaoyaosan acted on key targets such as albumin （ALB）， protein kinase B1 （Akt1）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF） through its main active components， including quercetin， kaempferol， β-sitosterol， and stigmasterol. These components were involved in the regulation of the advanced glycation end-products/receptor for advanced glycation end-products （AGE/RAGE） signaling pathway and the phosphoinositide 3-kinases（PI3K）/Akt signaling pathway in diabetic complications. The results of molecular docking showed that the key components of Xiaoyaosan had good binding capabilities with core targets， with β-sitosterol showing the strongest binding affinity with ALB. In vivo experiments demonstrated that Xiaoyaosan could significantly increase the protein and mRNA expression of ALB and Akt1 in serum， and inhibit the expression of IL-6 and TNF-α. It also significantly upregulated the expression of protein and mRNA of phosphorylation（p）-PI3K and p-Akt， and inhibited the RAGE expression. The results of cellular thermal shift assay （CETSA） showed that β-sitosterol could significantly inhibit the degradation of ALB protein. ConclusionXiaoyaosan may restore erectile function in diabetic rats by modulating targets such as ALB， Akt1， IL-6， and TNF， and through the RAGE/PI3K/Akt signaling pathway， and its main active component is likely β-sitosterol.

Changes in pharmacokinetics of single dose of fentanyl in simulated high altitude in rats / 陆军军医大学学报

Objective To explore the pharmacokinetic changes of single dose of fentanyl in rats in a simulated high-altitude and contributing factors.Methods Thirty-six healthy female SD rats(6～8 weeks old,250±20 g)were randomly divided into high-altitude-acute-exposure group(group A),high-altitude-chronic-exposure group(group S)and control group(group C)through random number table,with 12 rats in each group.The group A and S were housed in a low-pressure chamber simulating the high altitude of 5000 m above sea level for 3 and 30 d respectively,and the group C was housed out of the chamber(at an altitude of 300 m).A single dose of fentanyl was administered through the femoral vein to 6 rats randomly selected from each group.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to detect blood concentrations of fentanyl and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters,while blood samples were taken through the femoral artery before and in 1,2,4,8,15,30,60,120 and 180 min after administration.The remaining 6 rats were ultrasonographically assessed for portal vein internal diameter(PVD),peak flow velocity(PVV)and blood flow(PVF),and liver tissues were collected for CYP3A1 protein content assay.Results The blood drug concentrations of fentanyl in the group A and group S were significantly lower than those in the group C at 60,120,and 180 min(P=0.002,P＜0.001,P= 0.001).Compared with the group C,the clearance rate(CL)of the group A was increased by 54.06%(P=0.021),and the mean residence time(MRTlast)was shortened by 24.21%(P=0.033);CL of the group S was increased by 50.10%(P=0.041),the area under the concentration-time curve(AUC0-t,AUC0-∞)and MRTlast were reduced by 18.92%(P=0.039),27.54%(P=0.018)and 33.61%(P= 0.004),respectively.PVD and PVF in the group S increased by 10.87%(P=0.006)and 42.50%(P= 0.006)when compared with the group C.The CYP3A1 protein content in the group A was 28.74%,which was higher than that in the group C(P=0.048).Conclusion Fentanyl is cleared significantly faster after a single dose in rats in simulated high-altitude,which may be related to the increased liver blood flow and increased CYP3A1 protein expression in liver.

The characteristics of bone disseminated cells of 4T1 / 药学学报

Based on bone metastasis potential of mouse breast cancer 4T1 cells, the bone disseminated breast tumor cells 4T1 (B-4T1) were acquired through the screening of 6-mercaptopurine. The characteristics of B-4T1 were studied by morphological observation, proliferation assay, expression of epithelial and mesenchymal cell markers detection, transcriptome sequencing, and tumor formation experiments. The results showed that B-4T1 was round and spindle-shaped than primary 4T1 cells, and its proliferation rate was reduced, as well as epithelial cell adhesion molecule (EpCAM) and E-cadherin expression. The transcript level of N-cadherin was increased in the B-4T1, but not vimentin, indicating that B-4T1 had partial epithelial mesenchymal transition. Besides, B-4T1 had higher fatty acid metabolism and better tumor formation capacity. This study lays the experimental foundation for the basic study of metastasis in breast cancer. All animal experiments in this paper were conducted in accordance with the standards of the Animal Ethics Committee of China Pharmaceutical University.

Clinical Study on the Relationship between Gene Mutation Profile and Prognosis in Pediatric Acute Lymphocyte Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.@*METHODS@#Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL.@*RESULTS@#227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ2= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×109/L vs 8.23×109/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).@*CONCLUSION@#Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.

Clinical comprehensive evaluation of recombinant Mycobacterium tuberculosis fusion protein / 中国药房

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Current status and suggestions of home pharmacy services under the background of aging / 药学实践与服务

Objective To explore how to further improve the quality of home pharmacy services under the background of aging. Methods The development history of home pharmacy service in our country in recent years was summarized, and the current status and limitations of home-based pharmacy service were analyzed. Results Our country's home-based pharmacy service has gradually matured and standardized from the early stage of independent exploration in various regions, but its quality improvement is still restricted by multiple bottlenecks. It is recommended to increase the popularity of pharmacy services, broaden the promotion channels for rational drug use, and optimize the allocation of pharmacists. etc. to be improved. Conclusion It is of great significance to improve the quality of home-based pharmacy services for home-based patients in the community, and it requires the joint efforts of multiple parties to improve it.

Construction and in vitro evaluation of an LNP system for mRNA delivery / 药学实践与服务

Objective To construct lipid nanoparticles DLin-LNP for mRNA delivery. Methods DLin-LNP was prepared by thin film hydration method, and DLin-LNP/mRNA was further constructed by using EGFP-mRNA as model drug. The particle size, zeta potential, and appearance morphology were measured. Furthermore, the intracellular distribution and transfection of DLin-LNP/mRNA in RM-1 cells was investigated by laser scanning confocal microscope. Results DLin-LNP was successfully prepared. The average particle size was about (151.1±2.1) nm, the no-load potential was (23.7±0.5) mV. The cytotoxicity of DLin-LNP was far lower than that of the commercially available liposomal Lipo8000. The results of transfection experiment indicated that DLin-LNP has high transfection efficiency for mRNA delivery with low cytotoxicity and good stability. Conclusion DLin-LNP could become a potential mRNA vector for gene therapy.

Preparation, characterization and activity evaluation of Spirulina-chitooligosaccharides capable of inhibiting biofilms / 生物工程学报

The biofilms formed by pathogenic microorganisms seriously threaten human health and significantly enhance drug resistance, which urgently call for developing drugs specifically targeting on biofilms. Chitooligosaccharides extracted from shrimp and crab shells are natural alkaline oligosaccharides with excellent antibacterial effects. Nevertheless, their inhibition efficacy on biofilms still needs to be improved. Spirulina (SP) is a microalga with negatively charged surface, and its spiral structure facilitates colonization in the depth of the biofilm. Therefore, the complex of Spirulina and chitooligosaccharides may play a synergistic role in killing pathogens in the depth of biofilm. This research first screened chitooligosaccharides with significant bactericidal effects. Subsequently, Spirulina@Chitooligosaccharides (SP@COS complex was prepared by combining chitooligosaccharides with Spirulina through electrostatic adsorption. The binding of the complex was characterized by zeta potential, z-average size, and fluorescence labeling. Ultraviolet-visible spectroscopy (UV-Vis) showed the encapsulation efficiency and the drug loading efficiency reached up to 90% and 16%, respectively. The prepared SP@COS2 exhibited a profound synergistic inhibition effect on bacterial and fungal biofilms, which was mainly achieved by destroying the cell structure of the biofilm. These results demonstrate the potential of Spirulina-chitooligosaccharides complex as a biofilm inhibitor and provide a new idea for addressing the harm of pathogenic microorganisms.

The protective effect of cuminaldehyde on gastric mucosa in Rattus norregicus of experimental gastric ulcer / 中国药理学通报

Aim To explore the effect of cuminaldehyde in cumin fruit on gastric ulcer and the protective mechanism via establishing the gastric ulcer model of rats was by ethanol injury. Methods Thirty-six male R. norregicus were divided into six groups: control group, model group, omeprazole positive control group and cuminaldehyde low, medium and high dosage groups. After seven days of continuous intragastric administration, the acute gastric ulcer of R. norregicus was tested by absolute alcohol. Gastric ulcer area, inhibition rate, gastric tissue antioxidant activity, serum inflammatory factors and gastric mucosal protective factors were detected in different groups. Results The results showed that cuminaldehyde significantly reduced the area of gastric ulcer and increased the inhibition rate of gastric ulcer. The inhibition rate of cuminaldehyde at high dose group was up to 74.65%, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH) in gastric tissue significantly increased, and the contents of serum prolandin E

Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases) / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL).@*METHODS@#The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed.@*RESULTS@#Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ［(3.92-470)×109/L］ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%.@*CONCLUSION@#B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

Analysis on the management of type 2 inflammatory asthma from the guideline of Global Strategy for Asthma Management and Prevention / 中华预防医学杂志

Bronchial asthma is a common chronic respiratory disease, which is involved in a variety of cells and cellular components. In 2019, the guidelines for the diagnosis and treatment of asthma issued by the Global Initiative for Asthma (GINA) Committee put forward the concept of type 2 inflammatory asthma for the first time. The updated evolution of GINA guidelines has promoted the development of biological agents and disease treatment, providing effective prevention and treatment for patients with severe asthma and improving disease outcome. This paper expounds the disease mechanism and management suggestions of type 2 inflammatory asthma in GINA guidelines, and analyzes the relevant clinical studies on targeted treatment of type 2 inflammatory asthma in recent years, in order to provide reference for in-depth understanding of level 3 prevention and management of patients with type 2 inflammatory asthma.

Analysis on the management of type 2 inflammatory asthma from the guideline of Global Strategy for Asthma Management and Prevention / 中华预防医学杂志

Bronchial asthma is a common chronic respiratory disease, which is involved in a variety of cells and cellular components. In 2019, the guidelines for the diagnosis and treatment of asthma issued by the Global Initiative for Asthma (GINA) Committee put forward the concept of type 2 inflammatory asthma for the first time. The updated evolution of GINA guidelines has promoted the development of biological agents and disease treatment, providing effective prevention and treatment for patients with severe asthma and improving disease outcome. This paper expounds the disease mechanism and management suggestions of type 2 inflammatory asthma in GINA guidelines, and analyzes the relevant clinical studies on targeted treatment of type 2 inflammatory asthma in recent years, in order to provide reference for in-depth understanding of level 3 prevention and management of patients with type 2 inflammatory asthma.

Expert consensus on antiviral therapy of COVID-19 / 中华临床感染病杂志

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Interpretation of Teacher Training Syllabus for Clinical Pharmacist Training Program （2023 edition） / 中国药房

OBJECTIVE To interpret Teacher Training Syllabus for Clinical Pharmacist Training Program （2023 edition） （hereinafter referred as to the “new syllabus”）， and to provide reference and guidance for promoting the implementation of the new syllabus and realizing the quality-improving goal of the reform of the clinical pharmacist teacher training program initiated by China Hospital Association. METHODS From the perspective of the management and based on the position of the designer， the new syllabus was interpreted from four aspects： the background of its compilation and release， the process of its compilation and its characteristics， the key improvements of the program and the points for attention about its subsequent implementation. RESULTS & CONCLUSIONS The development and release of the new syllabus provide a “construction blueprint” for the reform of the clinical pharmacist teacher training program of the China Hospital Association. The whole process of compiling the new syllabus is characterized by four basic features： theory-led， goal-oriented， research-based， and synergistic. Compared with the previous syllabus， in addition to the adjustment of the text structure，the new syllabus presents more complete and clearer competence requirements for clinical teaching competence in terms of training objectives； in terms of training content， it further structures the group of task items， pays attention to the 育。E-mail：zhenjiancun@163.com sequential planning and time arrangement of items， and puts forward both quantitative and qualitative refinement requirements for each specific training task；in terms of training methods， it emphasizes the interaction of lecturing， demonstrating and guiding， and the progression of observation， operation and reflection， with the intention of guiding teacher trainees to “learn how to teach by teaching”. In the subsequent implementation of the new syllabus， it is necessary for the teacher training bases to attach great importance to the guarantee of training conditions and process quality management， and to organize the teacher training team to do a good job in the two training programs of “clinical pharmacist training” and “clinical pharmacist teacher training”. Based on further improving the connection between the two training programs， the teacher training team should continue to explore the scientific model of clinical pharmacist teacher training oriented by clinical teaching competence.

Multi-omics approaches for revealing the etiology of cancer: from genomics, exposomics, metabolomics to system epidemiology / 中华流行病学杂志

Identifying risk factors of the disease are one of the main tasks of epidemiology. With the advancement of omics technologies (e.g., genome, transcriptome, proteome, metabolome, and exposome), cancer etiology research has entered the stage of systems epidemiology. Genomic research identifies cancer susceptibility loci and uncovers their biological mechanisms. Exposomic research investigates the impact of environmental factors on biological processes and disease risks. The metabolome is downstream of biological regulatory networks, reflecting the effects of the gene, environment, and their interactions, which can help elucidate the biological mechanisms of genetic and environmental risk factors and identify new biomarkers. Here, we reviewed the applications of genomic, exposomic, and metabolomic studies in the etiologic research on cancer. We summarized the importance of multi-omics approaches and systems epidemiology in cancer etiology research and outlined future perspectives.

Discussion on the disposal methods and expiration extending strategy of expired drug in China / 中国药房

China produces about 15 000 tons of expired drugs every year. Standardized destruction of expired drugs consumes a large number of secondary costs， causing huge economic losses. Improper handling will also lead to serious environmental pollution， endanger national health and even endanger public safety. This paper analyzes the hazards， sources and disposal methods， and research status of expired drugs， introduces the Shelf-Life Extension Program of United States， and put forward feasible measures for the recovery， integration and reuse of expired drugs. It is suggested to construct a scientific and reasonable recovery and disposal system of expired drugs in combination with the actual situation in China， explore the strategy of extending the expiration of drugs， and greatly reduce the waste of drug resources.

A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model.

Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6-12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (Drd1-4) and synaptic proteins (Synaptophysin, PSD-95) were separately examined following 4 weeks of exercise in a subset of rats. Exercise/Lesion rats showed a modest, yet significant improvement in processing-related response accuracy in the 3-CSRT-R and T-maze, as well as a significant improvement in cognitive flexibility as assessed by inhibitory aptitude in the 3-CSRT-R. By four weeks, exercise also elicited increased expression of Drd1, Drd3, Drd4, synaptophysin, and PSD-95 in the dorsomedial and dorsolateral CPu. Our results underscore the observation that exercise, in addition to improving motor function may benefit cognitive performance, specifically EF, and that early changes (by 4 weeks) in CPu dopamine modulation and synaptic connectivity may underlie these benefits.

LncRNA Gaplinc promotes the pyroptosis of vascular endothelial cells through SP1 binding to enhance NLRP3 transcription in atherosclerosis.

Pyroptosis, characterized by activation of the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and its downstream effector inflammatory factors, has been shown to play a crucial role in atherosclerosis development. Long noncoding RNAs (lncRNAs) are involved in the progression of pyroptosis. However, the role and mechanism of the novel lncRNA gastric adenocarcinoma associated, positive CD44 regulator (Gaplinc), in endothelial cell pyroptosis during atherosclerosis development remain unexplored. Bioinformatics was performed to evaluate dysregulated lncRNAs in atherosclerotic mice fed a high-fat diet. The effect of Gaplinc on atherosclerosis progression in vivo was assessed via Oil Red O staining and fluorescence in situ hybridization. Its function in oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis of endothelial cells was determined through ectopic expression. Additionally, RNA pull-down and immunoprecipitation (RIP) assays were performed to determine Gaplinc and transcription factor SP1 interactions. Then the pyroptosis pathway proteins were analyzed via immunofluorescence and western blotting. We found that lncRNA Gaplinc was highly expressed in ox-LDL-induced endothelial cells as well as in the plaque and plasma of high-fat diet-treated ApoE-/- mice. Gaplinc silencing significantly inhibited endothelial cell pyroptosis and atherosclerotic plaque formation. Mechanistically, Gaplinc could interact with SP1 to bind to the NLRP3 promoter and upregulate the target gene expression of NLRP3, facilitating endothelial cell pyroptosis and atherosclerotic plaque enlargement in high- fat diet-fed mice. In conclusion, our results revealed the underlying mechanism of the lncRNA Gaplinc /SP1/NLRP3 axis in endothelial cell pyroptosis, which may provide new potential targets for the treatment of atherosclerosis.

Upregulation of microRNA-34a enhances myocardial ischemia-reperfusion injury via the mitochondrial apoptotic pathway.

Mitochondrial oxidative injury can result in many cardiovascular diseases including cardiac ischemia-reperfusion (I/R) injury. This study was designed to investigate whether microRNA-34a (miR-34a) influences cardiac I/R or hypoxia/reoxygenation (H/R) injury by regulating the mitochondrial apoptotic pathway from oxidative injury.In vivo, myocardial infarction size was examined by Evan blue/TTC staining. Apoptosis was assessed by TUNEL assay. Heart function was measured by echocardiography. Lactate dehydrogenase (LDH) and creatine kinase (CK) were evaluated. In vitro, H9c2 cardiomyocytes were exposed to H/R stimulation. Cell viability was assessed by the CCK-8 assay and apoptosis was detected by Annexin V/PI staining. Mitochondrial superoxide, mitochondrial membrane potential (MMP) and ATP production was evaluated by detection kits, and related proteins were detected by western blotting analysis. We observed that the level of miR-34a was significantly upregulated in I/R rats compared to the sham group. Injection of adenovirus inhibiting miR-34a into the left ventricular anterior wall improved heart function and decreased I/R injury. H9c2 cardiomyocytes exposed to H/R stimulation displayed an obvious increase in miR-34a expression. In addition, miR-34a inhibitor alleviated, whereas miR-34a mimic aggravated H/R-induced mitochondrial injury. Bcl-2 was identified as a target gene of miR-34a by dual-luciferase reporter gene detection. Knockdown of Bcl-2 abolished the cardioprotection of the miR-34a inhibitor in H9c2 cells. In summary,our study demonstrates that inhibition of miR-34a exhibits therapeutic potential in treatment of myocardial I/R injury by restraining mitochondrial apoptosis.

Construction and significance of prediction model for chronic obstructive pulmonary disease assessment test based on fusion deep network fused with air data / 中华健康管理学杂志

Objective:To construct a chronic obstructive pulmonary disease (COPD) assessment test (CAT) score prediction model based on a deep network fused with air data, and to explore its significance.Methods:From February 2015 to December 2017, the outdoor environmental monitoring air data near the residential area of the patients with COPD from the Respiratory Outpatient Clinics of Peking University Third Hospital, Peking University People′s Hospital and Beijing Jishuitan Hospital were collected and the daily air pollution exposure of patients was calculated. The daily CAT scores were recorded continuously. The CAT score of the patients in the next week was predicted by fusing the time series algorithm and neural network to establish a model, and the prediction accuracy of the model was compared with that of the long short-term memory model (LSTM), the LSTM-attention model and the autoregressive integrated moving average model (ARIMA).Results:A total of 47 patients with COPD were enrolled and followed up for an average of 381.60 days. The LSTM-convolutional neural networks (CNN)-autoregression (AR) model was constructed by using the collected air data and CAT score, and the root mean square error of the model was 0.85, and the mean absolute error was 0.71. Compared with LSTM, LSTM-attention and ARIMA, the average prediction accuracy was improved by 21.69%.Conclusion:Based on the air data in the environment of COPD patients, the fusion deep network model can predict the CAT score of COPD patients more accurately.