[Researchers' Knowledge About the Ethical Norms of National Natural Science Foundation of China Funded Medical Research:Current Status and Suggestions].

Objective To understand the current status of Chinese medical researchers' knowledge regarding the ethical norms of the research involving humans or laboratory animals,and provide reference for further improving the ethics review norms. Methods The questionnaire method was employed to survey the applicants for the 2019 projects supported by the Department of Medical Sciences,National Natural Science Foundation of China (NSFC) about their knowledge of ethical requirements.Furthermore,the ethical supervision of the NSFC and affiliations at the project application and implementation stages was analyzed. Results The survey showed that 29.9% medical researchers were familiar with NSFC's ethical requirements for research involving human or laboratory animals.During the project application stage,59.0% affiliations adopted the simplified review method.Regarding the ethical supervison,95.5% medical researchers believed that the affiliations should fulfill the ethical supervision obligations and take relevant measures during the project implementation period.In addition,55.0% medical researchers fully agreed to discuss with the review experts about the ethical issues involved in the project. Conclusions The NSFC should establish rules and regulations to improve institutional management responsibilities and institutionalize the training about research ethics to comprehensively strengthening the training.Taking the management of research project ethics as a starting point,the NSFC should form a multi-party linkage between project funding and management and establish an accountability mechanism for ethics management.Furthermore,the NSFC should double the endeavors at the review of ethical issues during expert review and process management and attach importance to the research,judgment,and prevention of ethical risks.

Microarray analysis of aberrant microRNA expression patterns in spinal cord gliomas of different grades.

MicroRNAs (miRNAs) are involved in the development of several types of tumor; however, their role in spinal gliomas remains unknown. The present study aimed to identify potentially novel spinal cord gliomas (SCG)-associated miRNAs and to characterize their roles in the development and progression of SCG. miRNA expression levels in low-grade SCG (classed as stage I-II SCG based on the World Health Organization grading system), high-grade SCG (classed as stage IV SCG based on the World Health Organization grading system) and 5 control cases were measured using a miRNA expression microarray. Subsequently, blood samples from the spinal cord of patients with differing grades of SCG were screened for differentially expressed miRNAs (DEmiRNAs). Compared with the control group, 7 upregulated and 36 downregulated miRNAs were identified in the low-grade SCG group and a total of 70 upregulated and 20 downregulated miRNAs were identified in the high-grade SCG group (P≤0.05, fold change >2). Gene Ontology analysis revealed that the regulation of cellular metabolic processes, negative regulation of biological processes and axon guidance were primarily involved. Moreover, pathway analysis showed that the target genes of DEmiRNAs were enriched in tumor-related signaling pathways, such as the MAPK and Wnt signaling pathway. The results suggest that DEmiRNAs in peripheral blood may serve as novel target markers with high specificity and sensitivity for the diagnosis of SCG.

A comparative study of microbial community and functions of type 2 diabetes mellitus patients with obesity and healthy people.

The gut microbiota is crucial in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the metabolism of T2DM patients is not well-understood. We aimed to identify the differences on composition and function of gut microbiota between T2DM patients with obesity and healthy people. In this study, 6 T2DM patients with obesity and 6 healthy volunteers were recruited, and metagenomic approach and bioinformatics analysis methods were used to understand the composition of the gut microbiota and the metabolic network. We found a decrease in the abundance of Firmicutes, Oribacterium, and Paenibacillus; this may be attributed to a possible mechanism and biological basis of T2DM; moreover, we identified three critical bacterial taxa, Bacteroides plebeius, Phascolarctobacterium sp. CAG207, and the order Acidaminococcales that can potentially be used for T2DM treatment. We also revealed the composition of the microbiota through functional annotation based on multiple databases and found that carbohydrate metabolism contributed greatly to the pathogenesis of T2DM. This study helps in elucidating the different metabolic roles of microbes in T2DM patients with obesity.

Publisher Correction: Comparison of Alterations in miRNA Expression in Matched Tissue and Blood Samples during Spinal Cord Glioma Progression.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Workplace violence against healthcare professionals in China: A content analysis of media reports.

Medical workplace violence (WPV) has become an alarming phenomenon in China. Few studies exist concerning how this is represented in the news. This study investigated the prevalence, characteristics, and causes of WPV from major news portals and medical websites in China, to provide a direction on the prevention and control of this issue. Quantitative content analysis was used to examine Chinese news portals and medical websites from 2013 to 2017. 235 valid reported cases were found. The number of incidents peaked in 2015, during the summer. Most cases occurred in the mid-eastern region of mainland China, in tertiary hospitals, and in the emergency department. The perpetrators were mainly individual males from the young adult or middle-aged groups. The major cause of medical WPV was dissatisfaction with treatment and referral. In conclusion, the development of prevention and control strategies is crucial and should be in accordance with the evidence from the research conducted.

Comparison of Alterations in miRNA Expression in Matched Tissue and Blood Samples during Spinal Cord Glioma Progression.

Abnormal expression of microRNAs (miRNAs) contributes to glioma initiation. However, the expression of miRNAs in tumour tissue or blood of spinal cord glioma (SCG) patients, particularly in high-grade spinal gliomas (Grade IV) known as glioblastoma (GBM), remains largely unknown. In this study we aimed to determine differentially expressed miRNAs (DEmiRNAs) in the tissue and blood between spinal cord glioblastoma (SC-GBM) patients and low grade SCG (L-SCG) patients. Additionally, we predicted key miRNA targets and pathways that may be critical in glioma development using pathway and gene ontology analysis. A total of 74 miRNAs were determined to be differentially expressed (25 upregulated and 49 downregulated) in blood, while 207 miRNAs (20 up-regulated and 187 down-regulated) were identified in tissue samples. Gene ontology analysis revealed multicellular organism development and positive regulation of macromolecule metabolic process to be primarily involved. Pathway analysis revealed "Glioma", "Signalling pathways regulating pluripotency of stem cells" to be the most relevant pathways. miRNA-mRNA analysis revealed that hsa-miRNA3196, hsa-miR-27a-3p, and hsa-miR-3664-3p and their target genes are involved in cancer progression. Our study provides a molecular basis for SCG pathological grading based on differential miRNA expression.

Baduanjin exerts anti-diabetic and anti-depression effects by regulating the expression of mRNA, lncRNA, and circRNA.

BACKGROUND: Baduanjin, a traditional Chinese exercise therapy, has been widely used in China to treat type 2 diabetes (T2DM) with depression (DD). However, the underlying mechanism of Baduanjin in anti-DD is unclear. This study was focused on investigating the effects of Baduanjin on symptoms of depression and blood glucose in patients with DD and the underlying mechanism. METHODS: We performed a 12-week Baduanjin intervention on patients with DD and longitudinally compared the differential expressions of lncRNAs, circRNAs, and mRNAs between pre- (BDD) and post- (ADD) Baduanjin intervention in the same group. Subsequently, Gene Ontology (GO) and pathway analysis was performed to investigate the function of differentially expressed mRNAs. Finally, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to verify the sequencing result and the mRNA-lncRNA regulatory network was constructed. RESULTS: The blood glucose level, depression index scores, and PHQ9 scores of the patients with DD were significantly decreased (P < 0.05) after Baduanjin intervention. Compared to BDD, 207 lncRNAs, 266 circRNAs, and 610 differentially expressed mRNAs were identified in ADD. Kyoto Encyclopedia of Genes and Genomes (KEGG) and GO showed that the significantly dysregulated mRNAs were mainly involved in immune function and inflammatory response pathways, and various signaling pathways including IL-17 and TNF. In addition, we selected five differentially expressed lncRNAs to construct an lncRNA-mRNA regulatory network, and found a total of 1045 mRNAs associated with them. CONCLUSIONS: Our research is the first systematic profiling of mRNA, lncRNA, and circRNA in patients of ADD and BDD, and provides valuable insights in the potential mechanism of Baduanjin in anti-DD. Further, it was confirmed that Baduanjin is a safe and effective intervention for patients with DD because it can effectively ameliorate the symptoms of depression and blood glucose levels in patients with DD by regulating the dysregulated expression of lncRNA, mRNA, and circRNA.

Experiments that led to the first gene-edited babies: the ethical failings and the urgent need for better governance.

The rapid developments of science and technology in China over recent decades, particularly in biomedical research, have brought forward serious challenges regarding ethical governance. Recently, Jian-kui HE, a Chinese scientist, claimed to have "created" the first gene-edited babies, designed to be naturally immune to the human immunodeficiency virus (HIV). The news immediately triggered widespread criticism, denouncement, and debate over the scientific and ethical legitimacy of HE's genetic experiments. China's guidelines and regulations have banned germline genome editing on human embryos for clinical use because of scientific and ethical concerns, in accordance with the international consensus. HE's human experimentation has not only violated these Chinese regulations, but also breached other ethical and regulatory norms. These include questionable scientific value, unreasonable risk-benefit ratio, illegitimate ethics review, invalid informed consent, and regulatory misconduct. This series of ethical failings of HE and his team reveal the institutional failure of the current ethics governance system which largely depends on scientist's self-regulation. The incident highlights the need for urgent improvement of ethics governance at all levels, the enforcement of technical and ethical guidelines, and the establishment of laws relating to such bioethical issues.

Silver-catalyzed C(sp2)-H functionalization/C-O cyclization reaction at room temperature.

Silver-catalyzed C(sp(2))-H functionalization/C-O cyclization has been developed. The scalable reaction proceeds at room temperature in an open flask. The present method exhibits good functional-group compatibility because of the mild reaction conditions. Using a AgNO3 catalyst and a (NH4)2S2O8 oxidant in CH2Cl2/H2O solvent, various lactones are obtained in good to excellent yields. A kinetic isotope effect (KIE) study indicates that the reaction may occur via a radical process.

[Clinical and imaging features and genetic analysis of a case with adult-onset Krabbe disease].

OBJECTIVE: To investigate clinical and imaging features of a patient with adult-onset Krabbe disease and to detect the underlying genetic mutations. METHODS: Clinical and cranial MRI features of the patient were analyzed. Pathogenesis, clinical manifestation, cranial MRI features and diagnostic criteria for the disease were discussed. RESULTS: The patient had presented asymmetric limb weakness and difficulty in walking. Electromyography suggested peripheral nerve demyelination. Cranial MRI showed increased signal intensity in white matter with involvement of the corticospinal tracts. Screening of GALC gene mutation has found the patient to be heterozygous for T1685C (Ile562Thr) and homozygous for A1921G (Thr641Ala), both of which were considered to be polymorphisms. In addition, he was heterozygous for G136T (Asp46Tyr), which had not been described previously. CONCLUSION: Clinical manifestations of adult-onset Krabbe disease may be atypical. Cranial MRI and galactocerebroside activity assay should be carried out for patients featuring chronic progressive corticospinal tract injury. An Asp46Tyr mutation probably underlies the disease in the current case.

Exploring the optimal operation time for patients with hypertensive intracerebral hemorrhage: tracking the expression and progress of cell apoptosis of prehematomal brain tissues.

BACKGROUND: Hypertensive intracerebral hemorrhage (HICH) is a severe disease with high morbidity and mortality. Timely removal of the hematoma through surgical procedures may effectively reduce secondary injuries. However, there has long been a debate over the proper timing of such surgery. In this study, we explored the optimal operation time for HICH patients by observing the pathological changes in perihematomal brain regions during different stages of onset. METHODS: Twenty-five specimens of brain tissue, obtained from perihematomal region of HICH patients in different phases, were subjected to haematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) staining and Caspase-3, matrix metalloproteinases-9 (MMP-9) immunohistochemical staining. The changing roles of necrosis and apoptosis and the expression of MMP-9 and Caspase-3 positive cells were all observed using image analysis. RESULTS: The obvious expression of TUNEL positive cells was recognized within 6 hours of ICH onset, reaching its peak between 6 hours and 24 hours in the early phase. RESULTS: were highly consistent with Caspase-3 and MMP-9 positive cell counts. Necrosis was found 6 hours after ICH onset and aggravated after 12 hours. CONCLUSIONS: In the early phase, apoptosis was seen as a major modality of injury in the brain tissue of the perihematomal region and was strongly correlated with the expression of MMP-9 and Caspase-3. The results of the present study suggest that an operation performed as soon as possible after ICH onset may be optimal for preserving the nervous system function.

[Guiding principles of clinical research on mild cognitive impairment (protocol)].

Mild cognitive impairment (MCI), as a nosological entity referring to elderly people with MCI but without dementia, was proposed as a warning signal of dementia occurrence and a novel therapeutic target. MCI clinical criteria and diagnostic procedure from the MCI Working Group of the European Alzheimer's Disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Beijing United Study Group on MCI funded by the Capital Foundation of Medical Developments (CFMD) proposed the guiding principles of clinical research on MCI. The diagnostic methods include clinical, neuropsychological, functional, neuroimaging and genetic measures. The diagnostic procedure includes three stages. Firstly, MCI syndrome must be defined, which should correspond to: (1) cognitive complaints coming from the patients or their families; (2) reporting of a relative decline in cognitive functioning during the past year by the patient or informant; (3) cognitive disorders evidenced by clinical evaluation; (4) activities of daily living preserved and complex instrumental functions either intact or minimally impaired; and (5) absence of dementia. Secondly, subtypes of MCI have to be recognized as amnestic MCI (aMCI), single non-memory MCI (snmMCI) and multiple-domains MCI (mdMCI). Finally, the subtype causes could be identified commonly as Alzheimer disease (AD), vascular dementia (VaD), and other degenerative diseases such as frontal-temporal dementia (FTD), Lewy body disease (LBD), semantic dementia (SM), as well as trauma, infection, toxicity and nutrition deficiency. The recommended special tests include serum vitamin B12 and folic acid, plasma insulin, insulin-degrading enzyme, Abeta40, Abeta42, inflammatory factors. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory. As measurable therapeutic outcomes, the primary outcome should be the probability of progression to dementia, the secondary outcomes should be cognition and function, and the supplement outcome should be the syndrome defined by traditional Chinese medicine. And for APOE epsilon4 carrier, influence of the carrier status on progression rate to dementia and the effect of treatment should be evaluated.

[An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)"].

In order to provide the "guiding principles of clinical research on mild cognitive impairment (MCI) (protocol)" edited by Beijing United Study Group on MCI of the Capital Foundation of Medical Developments (CFMD) with evidence support, clinical criteria, subtypes, inclusion and exclusion of MCI, and use of rating scales were reviewed. The authors suggested that MCI clinical criteria and new diagnosis procedure from the MCI Working Group of the European Alzheimer's disease Consortium (EADC) may better reflect the heterogeneity of MCI syndrome. Diagnostic rating scales including Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Instrumental Activities of Daily Living (IADL) are very useful in definition of MCI but can not replace its clinical criteria. Absence of major repercussions on daily life in patients with MCI was emphasized, but the patients may have minimal impairment in complex IADL. According to their previous research, the authors concluded that highly recommendable neuropsychological scales with cut-off scores in the screening of MCI cases should include Mini-Mental State Examination (MMSE), logistic memory test such as Delayed Story Recall (DSR), executive function test such as Clock Draw Test (CDT), language test such as Verbal Category Fluency Test (VCFT), etc. And finally, the detection of biological and neuroimaging changes, including atrophy in hippocampus or medial temporal lobe in patients with MCI, was introduced.

[Hearing impairment in senile dementia of Alzheimer's type].

OBJECTIVE: To evaluate the pure tone hearing threshold and word recognition score of senile dementia of the Alzheimer's disease (AD) patients, and to analyze the relationship between hearing loss and the cognition impairment. METHODS: Pure tone audiometry, word recognition score (WRS), acoustic immittance and auditory brainstem response (ABR) are used to evaluate the auditory function of 43 patients with AD and 50 subjects of the control group. The confounding factors are controlled. RESULTS: The average age of 43 dementia patients was 72.7 +/- 6.4, and 69.7% was female. Bilateral hearing thresholds are similar in all subjects. All indices but Mini-mental scale of equastionnaire (MMSE) of patients and control group were not statistically different. There was no significant difference in pure tone audiometry (PTA), PTA2 (dB HL, mean +/- s) and WRS (%, mean +/- s) between the two groups (P > 0.05), therefore the hearing threshold of AD group (PTA = 26.3 +/- 8.5, PTA2 = 29.1 +/- 8.7, WRS = 85.5 +/- 15.5) is lower than that of control group (PTA = 23.2 +/- 10.6, PTA2 = 26.2 +/- 11.8, WRS = 87.6 +/- 16.8). No significant difference was found between the two groups in audiometry reliability, acoustic immittance and ABR (P < 0.05). CONCLUSION: No significant difference was found between the peripheral hearing dysfunction of AD patients and that normal elderly people, i.e., PTA, PTA2 and WRS were not related to MMSE.

[Relationship between three neuropsychological tests and cerebral glucose metabolism in Alzheimer's disease].

OBJECTIVE: To study the relationship between the scores of 3 neuropsychological scales: MMSE, extended scale of dementia (ESD) and Blessed dementia scale (BDS) and cerebral glucose metabolism in Alzheimer's disease (AD) indicated by positron emission tomography (PET). METHODS: Brain scanning was performed with SIEMENS ECAT 47 PET scanner among 21 AD patients, aged 60 - 83 (10 mild, 6 moderate, and 5 severe), and 15 healthy persons, aged 57 - 73. The ratio of mean radioactivity of cerebral lobe to that of cerebellum as semi-quantitative parameters was used to evaluate the cerebral glucose metabolism. Cognitive function was assessed by three neuropsycholigical scales: MMSE, ESD and BDS. RESULTS: The average MMSE score was 13.3 +/- 6.3 (range 2 - 25), the average ESD score was 120.5 +/- 54.8 (range 28 - 200), and the average BDS score was 4.7 +/- 3.1 (range 0.5 - 10) in the AD patients. The decreases of glucose metabolism in parietal, frontal and temporal lobes were significantly positively correlated with MMSE and ESD scores, and negatively correlated with BDS scores in AD patients (P < 0.05). The correlations between MMSE and ESD (r = 0.886), MMSE and BDS (r = -0.763), and ESD and BDS (r = -0.773) were significant in AD patients (all P < 0.01). Taking the ratio of radioactivity of cerebral lobe to that of cerebellum as an independent variable X, the MMSE, ESD and BDS scorsas dependent variable Y, three regression equations were established as follows: Y = 40.11 * X- 25.32, Y = 309.19 * X- 180.9, Y = 19.97 - 16.53 * X. The independent variable entering the three regression equations was always the ratio of radioactivity of left parietal lobe to that of cerebellum. The ratio of radioactivity of left parietal lobe to that of cerebellum was a significant predictor for cognitive dysfunction measured by MMSE, ESD and BDS in AD patients (P < 0.01). CONCLUSION: MMSE, ESD and BDS scores correlate well with impaired cerebral glucose metabolism in AD. The function of left parietal lobe may play an important role in the progress of the disease. MMSE, ESD and BDS are good measures for cognitive dysfunction.