Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation / 医学前沿

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.

NF-κB regulates brown adipocyte function through suppression of ANT2

The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice [uncoupling protein 1 (Ucp1)-CreER-p65f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in cristae density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.

Postoperative changes in 25-hydroxy vitamin D and parathyroid hormone levels in obese patients / 中华临床营养杂志

Objective:To investigate the postoperative changes in levels of 25-hydroxy vitamin D (25-[OH]D], parathyroid hormone (PTH) and other relevant biomarkers in obese patients receiving metabolic surgery and analyze the dynamic changes in relevant biomarkers in the short term (after 3-6 months) and the long term (after 12-24 months).Methods:A total of 96 obese patients who underwent metabolic surgery and received follow-up examinations from January 2018 to January 2020 were included. Baseline and postoperative data were collected, including anthropometric data (height, weight, neck circumference, waistline and hipline) and laboratory test results (fasting glucose, glycated hemoglobin, 25-[OH)D, PTH, serum calcium and serum phosphorus). Body mass index (BMI) and waist-hip ratio were calculated. The anthropometric data were analyzed by repeated measures analysis of variance and laboratory data were compared between groups using t test and Kruskal-Wallis test. Results:96 patients (33 males and 63 females) were included, of whom 49 were complicated with diabetes. Prior to surgery, 79 (79.17%) of the patients had 25-(OH)D deficiency (< 20 μg/L), 16 (16.67%) had 25-(OH)D insufficiency (≥ 20 μg/L and < 30 μg/L) and 23 (23.96%) had high PTH levels (> 70 ng/L). After the surgery, 25-(OH)D level was transiently increased in the short term ( P = 0.01) but declined thereafter in the long term ( P < 0.01) to levels lower than baseline ( P = 0.023). Long-term PTH level was higher than baseline ( P = 0.012), with 11 patients showing PTH levels higher than normal (> 70 ng/L). Serum phosphorus level was increased in both the short term and the long term ( P < 0.01). Conclusions:Obese patients have 25-(OH)D deficiency/insufficiency before metabolic surgery and experience further decrease in the long term after surgery, despite a transient increase. Secondary increase in PTH level occurs in some of the patients after surgery. Long-term nutritional supplements and comprehensive nutritional management play important roles in postoperative management of obese patient.

Mitochondrial protein IF1 is a potential regulator of glucagon-like peptide (GLP-1) secretion function of the mouse intestine

IF1 (ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F

Clinical study on inflammatory response mediated tumor marker elevation in patients with type 2 diabetes mellitus: propensity matching study and mediating model study / 中国医师进修杂志

Objective:To compare the expression of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) between type 2 diabetes mellitus (T2DM) and non-diabetic patients, and investigate the role of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high sensitive C-reactive protein (hs-CRP) in the regulation of CA19-9 and CEA.Methods:From January to December 2016, a total of 146 patients with T2DM (T2DM group) were selected in Qinhuangdao Military Hospital of Hebei Province. According to age, gender, body mass index (BMI), waist circumference and hip circumference, propensity score was matched. A total of 146 healthy control group matches were completed according to the nearest neighbor matching method of 1∶1. According to the glycated hemoglobin (HbA 1c), the patients with T2DM were divided into 4 groups: HbA 1c<7% 16 cases (A subgroup), 7% ≤ HbA 1c<9% 38 cases (B subgroup), 9% ≤ HbA 1c<11% 44 cases (C subgroup), HbA 1c ≥ 11% 48 cases (D subgroup). The mediating effects of IL-6, TNF-α and hs-CRP in CA19-9 and CEA levels in patients with T2DM were determined by stepwise linear regression. Results:The fasting plasma glucose (FBG), HbA 1c, IL-6, TNF-α, hs-CRP, CA19-9 and CEA in T2DM group were significantly higher than those in control group: (9.95 ± 2.98) mmol/L vs. (4.89 ± 0.77) mmol/L, (9.85 ± 2.18)% vs. (5.71 ± 1.91)%, (46.51 ± 13.17) ng/L vs. (32.41 ± 13.74) ng/L, (45.41 ± 17.25) ng/L vs. (21.54 ± 15.01) ng/L, (4.99 ± 3.51) mg/L vs. (3.19 ± 3.15) mg/L, (13.35 ± 5.34) U/L vs. (8.58 ± 1.08) U/L and (2.51 ± 1.04) μg/L vs. (2.14 ± 1.01) μg/L, and there were statistical differences ( P<0.01). There were no statistical differences in gender composition, waist circumference, hip circumference, disease course and FBG among A subgroup, B subgroup, C subgroup and D subgroup ( P>0.05). There were statistical differences in the age, BMI, IL-6, TNF-α, hs-CRP, CA19-9 and CEA among 4 subgroups ( P<0.01 or <0.05). In patients with T2DM, the HbA 1c was positively correlated with IL-6, TNF-α, hs-CRP, CA19-9 and CEA ( r=0.863, 0.802, 0.495, 0.883 and 0.766; P<0.01). The IL-6, TNF-α and hs-CRP had some mediating effects in HbA 1c regulation of CA19-9: 20.5% (0.181/0.883), 17.8% (0.157/0.883) and 8.2% (0.072/0.883), respectively; the TNF-α had some mediating effect in HbA 1c regulation of CEA: 24.0% (0.184/0.766). Conclusions:There is a correlation between the levels of tumor markers and blood glucose in patients with T2DM, and inflammatory response is a potential regulatory variable.

Cluster analysis for syndromes of real-world coronary heart disease with angina pectoris / 医学前沿

Syndromes of coronary heart disease with angina pectoris were analyzed to provide guidance for clinical practice and to improve accuracy of traditional Chinese medicine (TCM) diagnoses and efficacy of TCM treatment. A total of 860 cases with coronary heart disease with angina pectoris were selected from TCM Clinical Research Information Sharing System for TCM clinics and research. Syndromes were automatically extracted with the cluster method and were analyzed to provide objective evidence for clinical studies. Final syndrome classifications were recognized and confirmed by clinical experts. Popular syndromes included Qi and blood deficiency, blood stasis and obstruction collaterals, liver depression and spleen deficiency, and Qi stagnation and blood stasis. Syndromes Qi and blood deficiency and blood stasis and obstruction collaterals accounted for 28.61% of total syndromes, whereas liver depression and spleen deficiency and Qi stagnation and blood stasis accounted for 26.44%. The main syndrome elements comprised Qi deficiency, blood deficiency, blood stasis, and Qi stagnation.

Clinical characteristics and prognosis of 34 cases of acute myeloid leukemia with FLT3 internal tandem duplication and MLL gene rearrangement / 中华血液学杂志

Objective@#To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) and MLL gene rearrangement.@*Methods@#The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stem cell transplantation (allo-HSCT).@*Results@#Of the thirty-four cases with median age 41 (4-71) years old, 63.6% presented with white blood cells (WBC) greater than 30×109/L, 39.4% greater than 50 × 109/L respectively on admission. M5 (35.3%) made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients (32.35%) had both FLT3-ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients (67.6%) had one or more other gene abnormalities (multiple gene abnormalities). Of the 34 cases, 29.4% patients went into complete remission (CR) after two courses of chemotherapy. 20.6% (7 patients) went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC>50×109/L or multiple gene abnormalities had a lower remission rate (7.7%, 5.4%) after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival (OS) in the 34 patients was 28.8% (95% CI 13.5%-46.0%) and the disease-free survival (DFS) was 27.1% (95% CI 12.5%-44.0%). Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% (95% CI 13.7%-70.4%) and DFS 42.7% (95% CI 13.4%-69.7%).@*Conclusion@#AML patients with FLT3-ITD and MLL gene rearrangement often presented with M5, accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.

A Systematic Review and Meta-Analysis on the Treatment of Primary Epilepsy with Settling and Quieting the Spirit and Resolving Phlegm / 世界科学技术-中医药现代化

Objective: To evaluate the clinical effects of combination of traditional Chinese and Western medicine in the treatment of primary epilepsy. Methods: The China Journal Full-text Database, science and Technology Journal Full-text Database, Wanfang database, PubMed database, EMbase were searched on the treatment of primary epilepsy literature combining traditional Chinese and Western medicine, and the system evaluation and meta-analysis were performed.Results: A total of 11 studies with 951 cases of primary epilepsy were included in the randomized controlled trial. The meta-analysis showed that the clinical effects of treatment of epilepsy group with combination of TCM and Western Medicine (RR=1.18, 95％ CI: 1.07-1.29, P ＜ 0.01), incidence frequency (WMD =-0.98, 95％ CI: 1.56-0.40), electrocardiogram improvement rate (RR=1.28, 95％ CI: 1.11-1.47, P ＜ 0.01) were significantly better than western medicine treatment (control group) . Conclusion: The effects of combined traditional Chinese and Western Medicine on primary epilepsy based on the method of latent town collaterals is superior to that of pure western medicine.

Study on Clinical Term Semantic Relationship of Traditional Chinese Medicine Based on Clustering / 世界科学技术-中医药现代化

The construction of clinical ontology of traditional Chinese medicine (TCM) is one of the important components of TCM internationalization.Among them,the study of clinical term entity has been quite successful.But the research on semantic relation is still lacking.This paper presented a method based on the combination of clustering and syntax pattern to study the semantic relations between TCM conceptual entities.By extracting the feature words around the entity,K-means was used as the clustering algorithm to perform the first round of clustering for all corpora.Based on results of the first round of clustering,the longest common subsequence was extracted in the same cluster and generalized as syntax pattern.According to the sentence after manual adjustment,it was automatically judged that each sentence in the corpus has the most suitable syntax pattern of semantic relations,and the second round of clustering is characterized by the syntax pattern.The result was the final clustering result.The experimental results showed that the accuracy of this method was 88.23％ for the classification of semantic relations in corpus.

Research on Data Collection Method in Real World Study of Traditional Chinese Medicine / 世界科学技术-中医药现代化

In real world clinical studies,standardized data acquisition method is a key step in the formation of reliable clinical evidence.This article described how to carry out clinical data collection and how to preprocess data in order to ensure the quality of data.The results showed that from the data sources,data collection contents,collection key points,data description and evaluation,this paper put forward the method of collecting the real world data of traditional Chinese medicine (TCM).It was concluded that the standardized methods of clinical data acquisition had laid a solid foundation for real world research.