Downregulation of Histone H4 Lysine 16 Acetylation Ameliorates Autophagic Flux by Resuming Lysosomal Functions in Ischemic Neurons.

Autophagic/lysosomal dysfunction was a critical pathogenesis of neuronal death after an ischemic stroke, but what drove the impairment of autophagic flux remained elusive. Studies indicated that histone H4 lysine 16 acetylation (H4K16ac) drastically modulated the autophagic/lysosomal signaling pathway. Herein, we investigated whether the autophagic/lysosomal dysfunction in neurons could be restored by altering H4K16ac levels after cerebral ischemia. The rat model of ischemic stroke and the cell ischemia model in HT22 neurons were prepared by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD), respectively. The result showed that H4K16ac could be effectively reduced by intracerebroventricular administration with MG149 (a H4K16ac inhibitor) after an ischemic stroke. Moreover, attenuated H4K16ac greatly alleviated the autophagic/lysosomal dysfunction in penumbral neurons, as indicated by decreased autophagic substrates of LC3-II, insoluble SQSTM1, and ubiquitinated proteins, accompanied by increased lysosomal cathepsin D. Conversely, treatment with trichostatin A (TSA, a H4K16ac facilitator) aggravated the impairment of autophagic flux. This regulative machinery of H4K16ac on the autophagic/lysosomal signaling pathway was also manifested in the OGD model of HT22 neurons. Furthermore, H4K16ac attenuation-ameliorated autophagic flux significantly alleviated stroke brain injury, as reflected by decreased infarct size, neuron loss, and neurological deficits. Similarly, the H4K16ac inhibition-mitigated autophagic/lysosomal dysfunction markedly promoted neuron survival and cell viability in OGD HT22 neurons. However, H4K16ac downregulation-ameliorated autophagic flux in neurons and thereby induced neuroprotection could be greatly counteracted by the lysosomal inhibitor bafilomycin A1 (Baf-A1). Our data indicate that cerebral ischemia-elevated H4K16ac creates the autophagic/lysosomal dysfunction due to lysosomal inefficiency, suggesting that H4K16ac attenuation benefits poststroke neuroprotection by resuming lysosomal functions in neurons.

What Do Patients Need in the Process of Constructing a Doctor-patient Community with a Shared Future / 中国医学伦理学

Constructing a doctor-patient community with a shared future requires efforts from both the medical supply side and the patient demand side, with special attention to the needs of patients. Continuously meeting and improving the needs of patients is the starting point, ultimate goal, and evaluation standard for constructing a doctor-patient community with a shared future. Therefore, this paper proposed the proposition of "what patients need", that is, what needs do patients have and how to meet their needs. The fundamental needs of patients are to diagnose and treat diseases and recover from illness, which are specifically manifested in the demands to narrate the disease’s feelings, the willingness to participate in medical decision-making, the experience of diagnosis and treatment in the process of medical treatment, and the satisfaction evaluation of the hospital’s performance appraisal. On the basis of clarifying the needs of patients, this paper proposed the paths and methods to meet patients’ needs, and provided new ideas for constructing a doctor-patient community with a shared future.

In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease.

The in situ metabolic profiling of the kidney is crucial to investigate the complex metabolic reprogramming underlying diabetic kidney disease (DKD) and to allow exploration of potential metabolic targets to improve kidney function. However, as the kidney is a highly heterogeneous organ, traditional metabolomic methods based on bulk analysis that produce an averaged measurement are inadequate. Herein, we employed an in situ metabolomics approach to discover alternations of DKD-associated metabolites and metabolic pathways. A series of histology-specific metabolic disturbances were discovered in situ using airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). In combination with integrated metabolomics analysis, five dysfunctional metabolic pathways were identified and located in the kidneys of type-2 DKD mice simultaneously for the first time, including taurine metabolism, arginine and proline metabolism, histidine metabolism, biosynthesis of unsaturated fatty acids, and fatty acid degradation pathways. As crucial nodes of metabolic pathways, five dysregulated rate-limiting enzymes related to altered metabolic pathways were further identified. These findings reveal alternations from metabolites to enzymes at the molecular level in the progression of DKD and provide insights into DKD-associated metabolic reprogramming.

Quality assessment of reports of clinical randomized controlled trials published in Chinese Journal of Dermatology from 2007 to 2016 / 中华皮肤科杂志

Objective To assess the quality of reports of clinical randomized controlled trials (RCTs) published in Chinese Journal of Dermatology from 2007 to 2016,and to provide a reference for standardization of clinical paper writing.Methods Based on the consolidated standards of reporting trials (CONSORT) 2010 statement,an evaluation form was designed and used to assess the quality of the clinical RCT articles published in Chinese Journal of Dermatology from 2007 to 2016.Results A total of 94 RCT articles were enrolled,including 45 articles from 2007 to 2011,and 49 articles from 2012 to 2016.Among these articles,the writing of introduction and discussion parts was relatively standardized.In the method and result parts,the proportions of articles correctly reporting blinding (23 articles,24.47％),sample size (0 article),primary and secondary outcome measures (21 articles,22.34％),participant flow (0 article),loss to follow-up (32 articles,34.04％) and compliance (13 articles,13.83％) were low,while the proportions of those correctly reporting inclusion and exclusion criteria,intervention measures,statistical methods,starting and ending time of follow-up and baseline data were all over 80％.Conclusion Most contents of the RCT articles published in Chinese Journal of Dermatology are standardized and clear,but the reporting of blinding,compliance,sample size,participant flow and so on,is insufficient,and close attention should be paid to these items.

Cost- effectiveness Analysis of Three Chemotherapy Schemes for Treatment of Advanced Non-small Cell Lung Cancer / 中国药房

OBJECTIVE: To investigate the economic effects of three chemotherapy schemes in the treatment of non-small cell lung cancer(NSCLC).METHODS:114 cases of advanced NSCLC were randomly divided into 3 groups, group MVP, group NP and group TP. The cost effectiveness of the 3 groups were compared using pharmaceutical economics. RESULTS: 3 schemes costed 1 875.2 yuan,5 565.2 yuan and 8 369.6 yuan respectively; The effective rates were 33.2%,34.1% and 40.5% respectively. On the basis of scheme MVP, scheme NP and TP increased cost of 4 100 yuan and 889.64 yuan respectively for 1% increase in effective rate. CONCLUSION: Scheme TP is the preferred choice.