Regulation of nucleo-cytosolic 26S proteasome translocation by aromatic amino acids via mTOR is essential for cell survival under stress.

The proteasome is responsible for removal of ubiquitinated proteins. Although several aspects of its regulation (e.g., assembly, composition, and post-translational modifications) have been unraveled, studying its adaptive compartmentalization in response to stress is just starting to emerge. We found that following amino acid starvation, the proteasome is translocated from its large nuclear pool to the cytoplasm-a response regulated by newly identified mTOR-agonistic amino acids-Tyr, Trp, and Phe (YWF). YWF relay their signal upstream of mTOR through Sestrin3 by disrupting its interaction with the GATOR2 complex. The triad activates mTOR toward its downstream substrates p62 and transcription factor EB (TFEB), affecting both proteasomal and autophagic activities. Proteasome translocation stimulates cytosolic proteolysis which replenishes amino acids, thus enabling cell survival. In contrast, nuclear sequestration of the proteasome following mTOR activation by YWF inhibits this proteolytic adaptive mechanism, leading to cell death, which establishes this newly identified pathway as a key stress-coping mechanism.

Lysyl oxidase interactions with transforming growth factor-ß during angiogenesis are mediated by endothelin 1.

Crosstalk between multiple components underlies the formation of mature vessels. Although the players involved in angiogenesis have been identified, mechanisms underlying the crosstalk between them are still unclear. Using the ex vivo aortic ring assay, we set out to dissect the interactions between two key angiogenic signaling pathways, vascular endothelial growth factor (VEGF) and transforming growth factor ß (TGFß), with members of the lysyl oxidase (LOX) family of matrix modifying enzymes. We find an interplay between VEGF, TGFß, and the LOXs is essential for the formation of mature vascular smooth muscle cells (vSMC)-coated vessels. RNA sequencing analysis further identified an interaction with the endothelin-1 pathway. Our work implicates endothelin-1 downstream of TGFß in vascular maturation and demonstrate the complexity of processes involved in generating vSMC-coated vessels.

Protective mechanisms of Tuina therapy against lipopolysaccharide-induced fever in young rabbits based on untargeted metabolomics analysis.

OBJECTIVE: To investigate the effect of Tuina on the plasma metabolites of lipopolysaccharide-induced febrile in infant rabbits. METHODS: Twenty-four infant New Zealand rabbits were selected and randomly divided into three groups: saline, model, and Tuina. The fever model was established by injecting LPS intravenously through the ear margin vein in the model group and Tuina group, respectively. The modeling was considered successful when the anal temperature increased by 0.5℃ or above within 1 h. In the Tuina group, six Tuina techniques (i.e., opening Tianmen / the heaven gate, pushing Kangong / the superciliary arch, kneading Taiyang and the prominent bone behind the ears, clearing Tianheshui, spine pinching) that alleviate fever were performed on the young rabbits 1 h after the modeling, whereas the model and saline groups were not given Tuina treatment, with the real-time anal temperature monitored during the experiment. The plasma was taken 3 h after the modeling for liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics study. RESULTS: Our results showed a fever-reducing effects of Tuina therapy on lipopolysaccharide-induced fever in young rabbits, as indicated by a significantly lower anal temperature, maximum rise in body temperature, and body response index at 2 and 3 h after modeling in the Tuina group compared to the model group, with reductions in the PGE2 expression observed in the blood and hypothalamus. The differential metabolites including riboflavin, nicotinamide N-oxide, porphobilinogen, 5-hydroxyindoleacetic acid, gamma-aminobutyric acid, and lysoPC (16:1 (9Z)/0:0) were found following the Tuina intervention. Tuina primarily involves glycine-serine-threonine, arginine-proline, porphyrin-chlorophyll, pyrimidine, primary bile acid biosynthesis, and cyanoamino acid metabolic pathways. CONCLUSION: Tuina therapy has proven to be effective in reducing body temperature and down-regulating PGE2 expression in LPS-induced febrile young rabbits, with its mechanism of fever-reducing action possibly associated with the changes in plasma metabolites and metabolic pathways.

Differences in health behavior and nutrient intake status between diabetes-aware and unaware Korean adults based on the Korea national health and nutrition examination survey 2016-18 data: A cross-sectional study.

Background: The aim of this study was to investigate the nutritional intakes and treatment regimens of Korean patients with type 2 diabetes who were aware of their condition. Methods: Participants (n = 16582) aged ≥ 19 years from the 2016-18 National Health and Nutrition Survey were divided into diabetes-aware and unaware groups and the variables were compared. Results: Among 1,906 (11.5%) diabetic adults, 1,433 (75.2%) were aware of their condition; 130 (9.1%) had nutrition education, and 1,340 (93.5%) were in the diabetes-aware treatment group. The diabetes-aware group had higher average age (P < 0.0001) and lower average BMI (P = 0.0015) than the unaware group. Intake of total fat (P = 0.0034), saturated fatty acids (P = 0.0021), riboflavin (P = 0.0035) and niacin (P = 0.0228) was significantly higher in the unaware group than in the diabetes-aware group, after adjusting energy intake for age and sex. Current smoking (P = 0.0046) and heavy drinking (P < 0.0001) rates were higher in the unaware group, whereas fiber intake (P = 0.0054) was lower in the unaware group. Higher levels of glycated hemoglobin were found in the group treated for diabetes (7.2%) than in the no-treatment (6.8%) group (P = 0.0048). Diabetes control was significantly better in the high income group. Conclusions: There is a need to strengthen nutritional education to prevent diabetes and improve the health status of diabetic patients in Korea.

TMAO as a potential biomarker and therapeutic target for chronic kidney disease: A review.

The gut microbiota and its metabolites have become a hotspot of recent research. Trimethylamine N-oxide (TMAO) metabolized by the gut microbiota is closely related to many diseases such as cardiovascular disease, chronic kidney disease, type 2 diabetes, etc. Chronic kidney disease (CKD) is an important contributor to morbidity and mortality from non-communicable diseases. Recently, increasing focus has been put on the role of TMAO in the development and progress of chronic kidney disease. The level of TMAO in patients with chronic kidney disease is significantly increased, and a high level of TMAO deteriorates chronic kidney disease. This article describes the relationship between TMAO and chronic kidney disease and the research progress of drugs targeted TMAO, providing a reference for the development of anti-chronic kidney disease drugs targeted TMAO.

[Seizure outcome after surgery for medically intractable mesial temporal lobe epilepsy and its predictors].

OBJECTIVE: To evaluate seizure outcome in patients receiving surgery for chronic medically intractable mesial temporal lobe epilepsy (MTLE) and analyze its possible predictors. METHODS: This retrospective study was conducted in patients with chronic medically intractable MTLE undergoing anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) in our department between September, 2011 and October, 2013. The patients were followed up for 3.5 to 5.5 years, during which the seizure outcome was evaluated according to Engel's classification. The clinical data were collected from the patients to identify the possible predictors that affected the outcome of the patients using Mann-Whitney U test or Kruskal-Wallis test. RESULTS: Atotal of 34 patients were included in this study with a definite diagnosis of chronic medically intractable MTLE after preoperative noninvasive and invasive evaluation. In 4 of these patients, invasive EEG monitoring confirmed that epileptic discharges originated from the bilateral mesial temporal lobe, and hence surgical resection of the epileptogenic zone was not performed. The other 30 patients underwent surgical resection of the epileptogenic zone with ALT or SAH, and favorable outcomes were achieved in 23 (76.7%) of the patients. Of the 7 (23.3%) patients with poor outcomes, 6 patients presented with typical automatism and aura with frequent secondary generalized tonic-clonic seizure, and the other one patient exhibited impaired intelligence. Statistical analysis suggested that the patients without a special disease history (trauma, febrile seizure, or encephalitis) tended to have a more favorable seizure outcome. CONCLUSIONS: Surgical interventions can achieve good therapeutic effect on chronic medically intractable MTLE, and patients without a special disease history may have more favorable outcomes after the surgery. SAH via the superior temporal sulcus approach can be a better surgical option for intractable MTLE.

Isoleucine and energy metabolism / 中华内分泌代谢杂志

The prevalence of energy metabolism-related metabolic diseases, such as diabetes, fatty liver, and cardiovascular diseases, is trending upwards over years. Not only glucose and lipid metabolism but also amino acid metabolism are involved in the pathogenesis, among which branched-chain amino acids are most widely studied. Isoleucine is an important branched-chain amino acid. Its relevance to metabolic diseases has caught more attention in recent years. This review is to highlight advances in isoleucine and energy metabolism.

Application of mixed TBL teaching method in practical teaching of critical obstetric diseases / 中华医学教育探索杂志

Objective:To evaluate the mixed team-based learning (TBL) teaching method in the practical teaching of critical obstetric diseases.Methods:A total of 72 undergraduate students majoring in "5+3" clinical medicine who practiced in The First Affiliated Hospital of Chongqing Medical University from April to June 2019 were selected in the study. The typical cases of obstetric critical illness were selected, and the students were taught by TBL teaching combined with flipped classroom. After the class, a questionnaire survey was conducted to evaluate the teaching effect.Results:Totally 72 questionnaires were recovered and the results showed that all the students thought this kind of mixed TBL teaching method was helpful to develop clinical thinking ability, and the process of "group discussion" and "extra-curricular preparation" was very helpful to understand the learning. A percentage of 93 (67/72) of the students liked this teaching mode, while 28% (20/72) of the students thought this learning mode was very stressful.Conclusion:This mixed TBL teaching method is effective and feasible in the practical teaching of critical obstetric diseases.

The application of organoid models in diabetes research / 中华内分泌代谢杂志

Organoids are complex tiny organ-like model systems formed by three-dimensional culture in vitro, based on the self-renew and self-organization of stem cells. This article reviewed the recent progress in organoids construction from tissues involved in the regulation of glucose homeostasis and chronic diabetic microvascular complications, and their applications in diabetes mellitus. Organoid technology is expected to further promote the progress of diabetes research in disease modeling, personalized medicine, and regenerative medicine.

Effects of gut microbiota on pharmacokinetics and its consideration in the evaluation of the consistency of quality and efficacy of generic drugs / 中国临床药理学与治疗学

Generic drugs account for more than 95% of the chemicals market in China, and their quality is directly related to the efficacy and safety of the people. The bioequivalence evaluation with pharmacokinetic parameters as the end point is the main content of the consistency evaluation of the quality and efficacy of generic drugs. Gut microbiota is considered to have an important influence on pharmacokinetics. This article reviewed the influence of gut microbiota on pharmacokinetics and analyzed its potential significance in the evaluation of the consistency of quality and efficacy of generic drugs.

Interpretation of the 2019 Guidelines for the Management of retinal vein occlusion by the EURETINA / 中华实验眼科杂志

Retinal vein occlusion (RVO) is the second common retinal vascular disease after diabetic retinopathy.The Management of Retinal Vein Occlusion-Consensus Document published in 2011 gave a comprehensive explanation of RVO diagnosis and treatment.While the European Society of Retina Specialists (EURETINA) updated the guideline for the management of RVO based on the 2011 consensus in August 2019.The current guideline summarized the latest clinical studies,and standardized the diagnosis and treatment of RVO based on stronger evidence-level data.The 2019 guidelines used the Rationale-Evidence-Recommendation structure to provide a comprehensive summary of RVO.

Interpretation of the 2019 Guidelines for the Management of retinal vein occlusion by the EURETINA / 中华实验眼科杂志

Retinal vein occlusion(RVO) is the second common retinal vascular disease after diabetic retinopathy.The Management of Retinal Vein Occlusion-Consensus Document published in 2011 gave a comprehensive explanation of RVO diagnosis and treatment.While the European Society of Retina Specialists (EURETINA) updated the guideline for the management of RVO based on the 2011 consensus in August 2019.The current guideline summarized the latest clinical studies, and standardized the diagnosis and treatment of RVO based on stronger evidence-level data.The 2019 guidelines used the Rationale-Evidence-Recommendation structure to provide a comprehensive summary of RVO.

Resveratrol improves high-fat diet induced insulin resistance by rebalancing subsarcolemmal mitochondrial oxidation and antioxidantion.

Although resveratrol (RES) is thought to be a key regulator of insulin sensitivity in rodents, the exact mechanism underlying this effect remains unclear. Therefore, we sought to investigate how RES affects skeletal muscle oxidative and antioxidant levels of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial populations in high-fat diet (HFD)-induced insulin resistance (IR) rats. Systemic and skeletal muscle insulin sensitivity together with expressions of several genes related to mitochondrial biogenesis and skeletal muscle SIRT1, SIRT3 protein levels were studied in rats fed a normal diet, a HFD, and a HFD with intervention of RES for 8 weeks. Oxidative stress levels and antioxidant enzyme activities were assessed in SS and IMF mitochondria. HFD fed rats exhibited obvious systemic and skeletal muscle IR as well as decreased SIRT1 and SIRT3 expressions, mitochondrial DNA (mtDNA), and mitochondrial biogenesis (p < 0.05). Both SS and IMF mitochondria demonstrated elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels. In addition, SS mitochondrial antioxidant enzyme activities were significantly lower, while IMF mitochondrial antioxidant enzyme activities were higher (p < 0.05). By contrast, RES treatment protected rats against diet induced IR, increased SIRT1 and SIRT3 expressions, mtDNA, and mitochondrial biogenesis (p < 0.05). Moreover, the activities of SS and IMF mitochondrial antioxidant enzymes were increased, which reverted the increased SS mitochondrial oxidative stress levels (p < 0.05). This study suggests that RES ameliorates insulin sensitivity consistent with improved SIRT3 expressions and rebalance between SS mitochondrial oxidative stress and antioxidant competence in HFD rats.

Research progress of optical coherence tomography angiography in retinal vein occlusion / 中华眼底病杂志

Retinal vein occlusion (RVO) is a vascular disease characterized by intraretinal hemorrhage,edema and hard exudation,which is caused by increased retinal vein pressure.OCT angiography (OCTA) has been widely used in the diagnosis of retinal vascular diseases including RVO by virtue of non-invasive,high resolution and stratified display of superficial,deep retinal vessels and quantification of retinal vessel density and non-perfusion area size.OCTA can provide information of retinal microvascular structure and blood perfusion under the condition of disease,it also can be used to evaluate the effect of treatment and changes of retinal circulation during the course of disease follow-up.Although OCTA cannot replace fundus angiography completely,it has brought us more information about the pathogenesis,disease progression and prognostic factors of RVO.It is believed that with the progress of technology,OCTA will bring us a new chapter in the study of retinal vascular diseases including RVO.

Advance and review: miniscrew-assisted rapid palatal expansion / 中华口腔医学杂志

Rapid palatal expansion (RPE) is commonly used to correct transverse maxillary deficiencies and recognized as a reliable orthopedic procedure in children and adolescents. For adults, however, conventional RPE has been considered rarely successful and can produce undesirable dental effects. Along with the development of digital techniques and mini-implant anchorage, a novel method called miniscrew-assisted RPE (MARPE) has become available for the treatment of maxillary transverse deficiency in older patients recently. In this article, the biomechanical principles and indications of MARPE, the advances in device design, the clinical effects, the matters needing attention and limitations of this method, and the stability after expansion are discussed.

Study on the correlation between smoking and hypothyroidism in iodine-suitable areas / 中华内分泌代谢杂志

Objective To explore the relationship between different smoking status and hypothyroidism in six iodine-suitable areas of China. Methods A total of 8187 residents were investigated by cluster sampling in six cities, and 7448 residents were included in the survey. The height, weight, waist circumference, and blood pressure were measured by filling out epidemiological questionnaire. Blood samples were collected to detect thyroid stimulating hormone ( TSH) , thyroid peroxidase antibody ( TPOAb) , and thyroglobulin antibody ( TgAb) . Results The mean TSH, TPOAb, and TgAb positive rates in passive smoking and active smoking groups were all lower than those in non-smoking group ( all P<0.01) . In the active smoking group, the TSH value decreased by 0.023 units for every unit increase in smoking index. The positive rates of TgAb and TPOAb in both passive smoking and active smoking groups were lower than those in non-smoking group (all P<0.01). Active and passive smoking reduced the prevalence of hypothyroidism (both P<0.01). Among women, the risks of clinical hypothyroidism and subclinical hypothyroidism were reduced in both active and passive smoking groups. Besides, the risk of subclinical hypothyroidism decreased significantly when the smoking index was more than 70. In male population, the risk of subclinical hypothyroidism in active and passive smoking group decreased. Besides, the risk of clinical hypothyroidism and subclinical hypothyroidism decreased significantly when the smoking index was more than 70. Conclusion Smoking in iodine-suitable areas may reduce TSH level and the positive rates of TPOAb and TgAb.

Progress of targeting inhibition of Sonic Hedgehog signaling pathway in leukemia / 白血病·淋巴瘤

Sonic Hedgehog (SHH) signaling pathway participates in the regulation of various organs and growth of tissue cells, maintains normal function and structure in the development of embryogenesis, however, SHH signaling pathway is in a state of inhibition. Meanwhile, the abnormal regulation of SHH signaling pathway plays an important role in the occurrence, development and drug resistance of leukemia. The mechanism of SHH signaling pathway in leukemia is similar to the solid tumor. With the further understanding of SHH signaling pathway, there are many antitumor drugs targeting SHH signaling pathway. The targeting inhibitors targeted SHH signaling pathway will become a new method for the treatment of leukemia. This paper reviews the application of the inhibitors targeting SHH signaling pathway in leukemia.

Discussion on teaching swstrategies of human anatomy for undergraduates of medical related majors / 中华医学教育探索杂志

Human body structure,as a national excellent course,is a professional basic course for the students in medical related majors.After years of teaching practice,many teaching experience are collected,however,some problems in teaching practice still occurre such as how to carry out teaching methods specific for different majors,how to accomplish the course for teachers and how to grasp the macro-and micro-cosmic human structures for students in fewer class hours,and how to improve the students' self-regulation of learning.Aiming at the problems above,the human body structure teaching team improves teaching methods,teaching content and assessment system,and effectively enhance the teaching effectivene.

Four years clinical follow-up and review analysis in a novel IBA57 mutation associated multiple mitochondrial dysfunction syndrome / 中华实用儿科临床杂志

Objective To investigate the clinical,imaging and IBA57 gene mutation features in a Chinese patient with multiple mitochondrial dysfunction syndrome,and to evaluated the effect of comprehensive rehabilitation.Methods The clinical data of 1 case of multiple mitochondrial dysfunction syndrome with IBA57 mutation in Department of Rehabilitation,Anhui Provincial Children's Hospital were analyzed."IBA57 white matter malnutrition" and "IBA57 leukodystrophy" were used as the key words,to search for papers which were included in CNKI,the knowledge service platform of Wanfang Data,and biomedical literature database (PubMed) from its establishment to February 2017.The clinical,imaging and gene mutation characteristics of children with IBA57 gene mutation were summarized.Results Children,male,four years and 8 months,for "movement disorders for nearly 4 years,repeated seizures 1 and a half years" in February 2017 hospitalized again.The boy was admitted into hospital when he was one year of age because of motor and cognitive disorder after fever,Disease was development,The skull MRI showed multiple abnormal signal in bilateral frontal occipital lobe and semi-oval center white matter.Cognitive and verbal improvement was better,and the motor function gradually improved after repeated rehabilitation in our hospital,skull MRI showed that multiple abnormalities were reduced in bilateral frontal occipital lobe and semi-oval center white matter.However,The boy presented twitch when he was three years and 2 months old.Skull MRI showed that multiple abnormal signal increased in bilateral forehead occipital lobe and semi-oval center white matter in four years and 3 months and 6 months of age.The child was diagnosed with white matter disease after multiple hospitalizations,and c.286T ＞ C (p.Tyr86 His) and c.1053 G ＞ A (p.Trp351 *) were found in the IBA57 gene through exome sequencing analysis,as the 2 mutations constituted complex heterozygous mutation.The former was inherited from the mother,and the mutation was missense mutation,so the protein structure was predicted to be harmful;the latter was inherited from the father,and the mutation was nonsense mutation,which could lead to the coding protein truncation,and this was never reported before.The child was diagnosed as multiple mitochondrial dysfunction syndrome type 3,followed by treatment with high-dose coenzyme Q10,ATP,compound vitamin B and others.While taking levetiracetam and topiramate antiepileptic,and family rehabilitation,his condition was stable.Conclusion The extensive white matter lesions presented in the child may be caused by mitochondrial disease with IBA57 gene mutation.