Predicting coronary heart disease in Chinese diabetics using machine learning.

Diabetes, a common chronic disease worldwide, can induce vascular complications, such as coronary heart disease (CHD), which is also one of the main causes of human death. It is of great significance to study the factors of diabetic patients complicated with CHD for understanding the occurrence of diabetes/CHD comorbidity. In this study, by analyzing the risk of CHD in more than 300,000 diabetes patients in southwest China, an artificial intelligence (AI) model was proposed to predict the risk of diabetes/CHD comorbidity. Firstly, we statistically analyzed the distribution of four types of features (basic demographic information, laboratory indicators, medical examination, and questionnaire) in comorbidities, and evaluated the predictive performance of three traditional machine learning methods (eXtreme Gradient Boosting, Random Forest, and Logistic regression). In addition, we have identified nine important features, including age, WHtR, BMI, stroke, smoking, chronic lung disease, drinking and MSP. Finally, the model produced an area under the receiver operating characteristic curve (AUC) of 0.701 on the test samples. These findings can provide personalized guidance for early CHD warning for diabetic populations.

A novel insight for high-rate and low-efficiency glucose metabolism in depression through stable isotope-resolved metabolomics in CUMS-induced rats.

BACKGROUND: Existing research has suggested that depression results in disorders of glucose metabolism in the organism which causing insufficient energy supply. However, the overall changes in glucose metabolism that arise from depression have not been clarified. METHODS: In this study, the depression-like behavior in chronically unpredictable mild stressed rats was investigated, and the fate of glucose was tracked through isotope tracing and mass spectrometry, with a focus on metabolite changes in cecal contents. RESULTS: As indicated by the results, the isotopic results of cecal contents can indicate the metabolic end of the organism. Moreover, the TCA cycle activity was notably reduced, and the gluconeogenesis pathway was abnormally up-regulated in the CUMS-induced rats. The organism expedited other glucose metabolism pathways to make up for the insufficiency of energy. As a result, the activity of the inefficient glycolysis pathway was increased. LIMITATIONS: Existing research has only investigated the metabolism of 13C-glucose, and lipids and proteins have been rarely explored. CONCLUSIONS: The chronic unpredictable mild stress can inhibit the entry of pyruvate into mitochondria in SD rats, such that the activity of TCA is reduced, and insufficient energy supply is caused. The organism is capable of expediting other glucose metabolism rate pathways to make up for the insufficiency of energy, whereas it still cannot compensate for the loss of energy. As a result, CUMS-induced rats exhibited high-rate and low-efficiency glucose metabolism.

Causal relationship between serum uric acid and abnormal blood pressure based on the panel model study: A 5-year cohort study.

BACKGROUND AND AIMS: To investigate the relationship between elevated serum uric acid (SUA) levels and blood pressure (BP). METHODS AND RESULTS: Based on the Beijing Health Management Cohort, 5276 health examination people were enrolled. Cross-lagged model was used to explore the relationship between SUA levels and blood pressure. The results showed: (1) increased SUA and increased systolic blood pressure (SBP): ① The path coefficients from baseline SUA to follow-up SBP were statistically significant in both the general population (ß = 0.034, P < 0.05) and men (ß = 0.048, P < 0.05). The path coefficients from baseline SBP to follow-up SUA were not statistically significant in either the general population (ß = 0.010, P > 0.05) or men (ß = 0.011, P > 0.05). ② The path coefficients from baseline SUA to follow-up SBP and from baseline SBP to follow-up SUA were not statistically significant in women with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2. (2) Increased SUA and diastolic blood pressure (DBP): ① There was no statistical significance between the path coefficients from baseline DBP to follow-up SUA and the path coefficients from baseline SUA to follow-up DBP. ② In men and women, BMI ≥ 25 kg/m2 and BMI < 25 kg/m2, the path coefficients from baseline DBP to follow-up SUA and from baseline SUA to follow-up DBP were not statistically significant. CONCLUSIONS: SUA can increase blood pressure in the general male population; no reverse time sequence relationship was found. The temporal relationships between SUA levels and SBP abnormalities were different in the sex and BMI subgroups. No bidirectional causal temporal relationship was found between SUA elevation and DBP abnormality.

Risk prediction of diabetes and pre-diabetes based on physical examination data.

Diabetes is a metabolic disorder caused by insufficient insulin secretion and insulin secretion disorders. From health to diabetes, there are generally three stages: health, pre-diabetes and type 2 diabetes. Early diagnosis of diabetes is the most effective way to prevent and control diabetes and its complications. In this work, we collected the physical examination data from Beijing Physical Examination Center from January 2006 to December 2017, and divided the population into three groups according to the WHO (1999) Diabetes Diagnostic Standards: normal fasting plasma glucose (NFG) (FPG < 6.1 mmol/L), mildly impaired fasting plasma glucose (IFG) (6.1 mmol/L ≤ FPG < 7.0 mmol/L) and type 2 diabetes (T2DM) (FPG > 7.0 mmol/L). Finally, we obtained1,221,598 NFG samples, 285,965 IFG samples and 387,076 T2DM samples, with a total of 15 physical examination indexes. Furthermore, taking eXtreme Gradient Boosting (XGBoost), random forest (RF), Logistic Regression (LR), and Fully connected neural network (FCN) as classifiers, four models were constructed to distinguish NFG, IFG and T2DM. The comparison results show that XGBoost has the best performance, with AUC (macro) of 0.7874 and AUC (micro) of 0.8633. In addition, based on the XGBoost classifier, three binary classification models were also established to discriminate NFG from IFG, NFG from T2DM, IFG from T2DM. On the independent dataset, the AUCs were 0.7808, 0.8687, 0.7067, respectively. Finally, we analyzed the importance of the features and identified the risk factors associated with diabetes.

First report of Colletotrichum fioriniae causing leaf spot on Schima superba in the world.

Schima superba Gardn. et Champ. is a subtropical evergreen tree species naturally distributed mainly in China, Japan, and Vietnam. It is primarily planted for its timber and urban landscaping in China (Ni, 1996). In September 2018, leaves necrotic spots were observed on S. superba in Jiangxi Forest Breeding Center (28°57'19.52" N, 115°39'21.32" E), Jiangxi Province, China. The disease incidence was about 30%. Initially, spots were circular to semicircular, grayish-brown in the center with dark brown margin, then expanded and eventually collapsed into sunken necrotic lesions. To identify the agent, diseased leaves were collected randomly. Pieces (5 × 5 mm) from the lesion borders were surfaced sterilized in 70% ethanol (30 s), 3% NaOCl (60 s), and rinsed 3 times in sterile water. These pieces were put on potato dextrose agar (PDA) and cultured at 25 °C. Pure cultures were obtained by monosporic isolation, and 3 isolates (MH-1, MH-2, MH-3) were used for morphological studies and phylogenetic analyses. On PDA, colonies were initially white, cottony, then became pinkish to deep-pink at the center and pink on the reverse. Conidia were fusiform with acute ends, smooth-walled, hyaline, 13.7-18.5 × 4.6-6.1 µm (16.4 ± 1.3× 5.3 ± 0.6 µm, n = 100). Conidiophores were colorless to pale brown, smooth, septate. Conidiogenous cells were colorless to pale brown, smooth, cylindrical to ampulliform. The morphological characteristics fit the descriptions of Colletotrichum acutatum J. H. Simmonds sensu lato (Damm et al., 2012). For accurate identification, genomic DNA of 3 isolates was extracted, and the internal transcribed spacer (ITS), actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-tubulin 2 (TUB2), and chitin synthase (CHS-1) were amplified and sequenced using the corresponding primers (Weir et al., 2012). The sequences were deposited in GenBank (ITS: MZ325946, MZ325947, MW584318; ACT: MZ399375, MZ419566, MW661171; CHS-1: MZ399376, MZ419567, MW661172; MZ399377, GAPDH: MZ419568, MW661173; TUB2: MZ399378, MZ419569, MW661174). Five loci were concatenated, and the aligned sequences (1528bp) were 99.89% homologous to ex-type C. fioriniae (Marcelino & Gouli) R. G. Shivas & Y. P. Tan CBS128517. Phylogenetic analysis using the maximum likelihood showed that 3 isolates were clustered in C. fioriniae clade with 100% bootstrap support. Based on the multi-locus phylogeny and morphology, 3 isolates were identified as C. fioriniae. Pathogenicity tests were performed on 36 seedlings of S. superba (2-year-old). The leaves were wounded slightly and inoculated with a drop of spore suspension (106 conidia/mL). The sterile water was used as controls. All the tested leaves were covered with black plastic bags to keep them moist for 2 days. All seedlings were placed in the greenhouse (25 °C, 12 h light/dark) for 10 days, and all inoculated leaves had typical symptoms. The controls were asymptomatic. The same fungus was reisolated from the lesions, fulfilling Koch's postulates. Colletotrichum fioriniae was described as a new species from the C. acutatum s. l. (Shivas et al., 2009), and it was an important plant pathogen, such as Pyrus spp. (Pavlovic et al., 2019), Morus alba L. (Xue et al., 2019), and so on. This is the first report of the newly emerging disease of S. superba caused by C. fioriniae in the world, and its potential threat should be evaluated in the future. This study provided crucial information for epidemiologic studies and appropriate control strategies.

Stable Isotope-Resolved Metabolomics Reveals the Abnormal Brain Glucose Catabolism in Depression Based on Chronic Unpredictable Mild Stress Rats.

The severe harm of depression to human life has attracted great attention to neurologists, but its pathogenesis is extremely complicated and has not yet been fully elaborated. Here, we provided a new strategy for revealing the specific pathways of abnormal brain glucose catabolism in depression, based on the supply of energy substrates and the evaluation of the mitochondrial structure and function. By using stable isotope-resolved metabolomics, we discovered that the tricarboxylic acid cycle (TCA cycle) is blocked and gluconeogenesis is abnormally activated in chronic unpredictable mild stress (CUMS) rats. In addition, our results showed an interesting phenomenon that the brain attempted to activate all possible metabolic enzymes in energy-producing pathways, but CUMS rats still exhibited a low TCA cycle activity due to impaired mitochondria. Depression caused the mitochondrial structure and function to be impaired and then led to abnormal brain glucose catabolism. The combination of the stable isotope-resolved metabolomics and mitochondrial structure and function analysis can accurately clarify the mechanism of depression. The mitochondrial pyruvate carrier and acetyl-CoA may be the key targets for depression treatment. The strategy provides a unique insight for exploring the mechanism of depression, the discovery of new targets, and the development of ideal novel antidepressants. Data are available via ProteomeXchange with identifier PXD025548.

Imbalance of T-helper 17 and regulatory T cells in patients with alopecia areata.

There is mounting evidence that T helper (Th)17 cells and regulatory T cells (Treg) play parts in the pathogenesis of autoimmune disease. Hence, levels of these T-cell subsets in patients with alopecia areata (AA) merit investigation. Our goal was to assess Th17 and Treg levels in peripheral blood mononuclear cells (PBMC) and scalp lesions of patients with AA, correlating the findings with clinical characteristics. PBMC of 177 patients with AA (test group) and 42 healthy controls and scalp tissues of 33 patients and 15 healthy controls were collected. Levels of Th17 and Treg subsets were then determined via flow cytometry and immunohistochemical staining, correlating results in test subjects with clinical features of AA. Th17 levels were significantly higher in patients, whereas Treg levels were lower by comparison. Furthermore, Th17 levels in patients with disease of short duration or in the active phase were significantly higher, relative to their respective counterparts. Th17 levels also negatively correlated with disease duration. While Treg levels were higher in severe AA than in mild AA. Results of lesions were parallel to findings of PBMC. Our data indicates an imbalance in the immune state of patients with AA.

Electrochemical Behavior of Al-B4C Metal Matrix Composites in NaCl Solution.

Aluminum based metal matrix composites (MMCs) have received considerable attention in the automotive, aerospace and nuclear industries. One of the main challenges using Al-based MMCs is the influence of the reinforcement particles on the corrosion resistance. In the present study, the corrosion behavior of Al-B4C MMCs in a 3.5 wt.% NaCl solution were investigated using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) techniques. Results indicated that the corrosion resistance of the composites decreased when increasing the B4C volume fraction. Al-B4C composite was susceptible to pitting corrosion and two types of pits were observed on the composite surface. The corrosion mechanism of the composite in the NaCl solution was primarily controlled by oxygen diffusion in the solution. In addition, the galvanic couples that formed between Al matrix and B4C particles could also be responsible for the lower corrosion resistance of the composites.

[A method of screening the antitumor lead compounds based on the dynamic bio-response profile of cells].

The study is to report the establishment of a method of screening the antitumor compounds based on the dynamic bio-response profile of cells to make up for the shortages of conventional end-point tests such as tedious operation and low sensitivity. Based on the principle of electric impedance of cells, the real-time cell electronic sensing (RT-CES) system was used to monitor the effect of epirubicin (EPI), cisplatinum (DDP) and carboplatin (CBP) on the growth of HepG2 cells, with the cell index (CI), half maximal inhibitory concentration (IC50) and detachment curve as evaluation indexes. Meanwhile, cell counting kit-8 (CCK-8) and microscopy were applied for verification. The results showed that CI curve could sensitively real-time profile the inhibitory effect of model drugs on HepG2 cells. The IC50 of EPI, DDP and CBP were 0.53 +/- 0.04, 9.79 +/- 0.26 and 597.00 +/- 3.79 microg x mL(-1), respectively. What's more, the significant differences of detachment curves of the three drugs indicated that their functional mechanisms might be different, this is consistent with the literature. The RT-CES system with non-invasive, label-free and real-time characteristics could be used to monitor the bio-response profile of the three drugs to HepG2 cells, allowing to qualitatively and quantitatively distinguish the antitumor activities of the three drugs, and could be a complementary method for the present screening of antitumor compounds.

Clinical and pathological study of 328 cases of actinic keratosis in eastern chinese patients.

BACKGROUND: Actinic keratosis (AK) is prevalent and has been widely studied in fair-skinned populations. However, this is not the case in eastern countries. AK in Asians has not been so thoroughly investigated. OBJECTIVES: To analyse the clinical and pathological features of a relatively large number of cases of AK diagnosed in older Chinese patients. METHODS: Case histories of 328 patients with pathologically diagnosed AK were analysed retrospectively. Their demographic, clinical, pathological and treatment data were collected for analysis of associated factors. RESULTS: Lesions were usually distributed on the face, especially the cheeks and temples. The most frequent pathological type was hypertrophic. Only 34% of the cases had been diagnosed correctly as AK before biopsy; many were mistaken for seborrhoeic keratosis. CONCLUSIONS: Most patients were elderly females and there was a higher incidence of lesions on the face, and a lower incidence on the extremities and trunk; this finding contrasts with previous investigations in fair-skinned people.

A strategy for trade monitoring and substitution of the organs of threatened animals.

The use of threatened animals as a source of traditional medicines is accelerating the extinction of such species and imposes great challenges to animal conservation. In this study, we propose a feasible strategy for the conservation of threatened medicinal animals that combines trade monitoring and the search for substitutes. First, DNA barcoding provides a powerful technique for monitoring the trade of animal species, which helps in restricting the excessive use and illegal trade of such species. Second, pharmacological tests have been adopted to evaluate the biological equivalence of threatened and domestic animals; based on such testing, potential substitutes are recommended. Based on a review of threatened animal species and their substitutes, we find that the search for substitutes deserves special attention; however, this work is far from complete. These results may be of great value for the conservation of threatened animals and maintaining the heritage of traditional medicine.

[Investigation on correlation between ratio of xylem to phloem of Radix Isatidis and efficacy, chemical composition].

OBJECTIVE: Explore contribution of ratio of xylem to phloem(RXP) to evaluate the quality of Radix Isatidis. METHODS: Antivirus activity and chemical compositions of xylem, phloem and Radix Isatidis of different RXP were determined by RBC agglutination test and unique chromatogram. Meanwhile, correlation between RXP and bioactivity,components was investigated. RESULTS: the activity of medical material of Radix Isatidis whose RXP was 1:2 or 1:1 is equal to that of phloem sample, while is stronger than that of cylem sample. There was a good consistency among the chemical figureprints of three samples (Radix Isatidis, xylem and phloem). When the RXP was 2:1, the medical material of Radix Isatidi and its xylem had the same activity. But the activity of phloem was not obvious. Their consistency of chemical fingerprint was bad, and the activity of Radix Isatidis which had RXP of 1:2 or 1:1 was better than that formed by xylem and phloem of 2:1. The Radix Isatidis of RXP of 1:2 or 1:1 had less similarity of chemical figureprint with that having RXP of 2:1. CONCLUSION: The quality of Radix Isatidis made up by the various RXP had significant difference. Radix Isatidis whose RXP is less than 1:1 had good quality and better activity. As a characteristic parameter of biologic morpha, the RXP can be applied to identifying the quality of Radix Isatidis, and also provided a reference to evaluation of other medical material of roots.

[Compatibility evaluation of Chinese medicines injections based on isothermal titration calorimetry].

The paper is to report the establishment of a method for quickly evaluating compatibility of Chinese medicines injections. Isothermal titration calorimetry (ITC) was used to evaluate compatibility of Yiqifumai (YQFM) and vitamin C injection (Vc)/5% glucose injection (5% GS). The diversification of Gibbs free energy (deltaG), enthalpy (deltaH) and entropy (deltaS) were used to decide reaction types of colliquefaction procedures of different injections. The reactive profiles were used to determine signs and quantity of heat. And high performance liquid chromatography (HPLC) was used as a supportive method for ITC. Then, feasible binding sites were analyzed based on the information of spatial structures of major compositions. During the colliquefaction procedure of YQFM and Vc, [deltaH] > T[deltaS], so, the reaction is enthalpy-driving. And the reactive profile showed that a big deal of heat was given out during the procedure. Obviously, chemical reactions happened and the major compositions changed. On the other side, the reaction of YQFM mixed with 5% GS was entropy-driving, because [deltaH] < T[deltaS]. The reactive profile showed there was a little heat gave out. So, non-chemical reactions happened, and the major compositions did not change. The conformity existed between the results of ITC and HPLC. ITC could be used to evaluate the compatibility of Chinese medicines injections because of the advantages of ITC, such as real time, fast, sensitive and having more parameters.

Applications of microcalorimetry in the antibacterial activity evaluation of various Rhizoma coptidis.

CONTEXT: Various Rhizoma coptidis are commonly used in clinical applications due to their strong antibacterial effect. OBJECTIVE: The antibacterial effect of various R. coptidis were evaluated by microcalorimetry together with statistical analysis. MATERIALS AND METHODS: The dried roots of Coptis chinensis Franch, Coptis deltoidea C.Y. Cheng et Hsiao, and Coptis teeta Wall (Ranunculaceae) were identified by Prof. Xiao-He Xiao. The herbs were tested using thermal activity monitor (TAM) air isothermal microcalorimeter, ampoule mode, to evaluate the biological activity. The dynamic energy metabolism information about the Staphylococcus aureus growth at 37°C was analyzed with principal component analysis. RESULTS: From the principle component analysis on quantitative parameters, the action of various R. coptidis on S. aureus growth at 37°C could be easily evaluated by analyzing the change of values of the two main parameters: the growth rate constant of first stage (k(1)) and the maximum heat rating of the first stage (P(1)). And the results of paired t-test show that there were no notable differences between inhibitory ratios calculated with k(1) and that of P(1). Using microdilution method, the minimal inhibitory concentrations (MIC) of C. chinensis, C. deltoidea, and C. teeta were detected, and they were 77.8 ± 2, 116.6 ± 4, 93.3 ± 2 µg/mL, respectively. DISCUSSION AND CONCLUSION: This work provided a useful method for the evaluation of antibacterial activity of various R. coptidis.

[Investigation on the process of sapindus saponin purified with macroporous adsorption resin and screening of its bacteriostasis].

OBJECTIVE: To study the technological parameters of the purification process of saponins with macroporous adsorption resin. METHODS: The adsorptive characteristics and elutive parameters of the process were studied by taking the elutive and purified ratio of saponins as markers. Bacteriostasis activity of each parts eluted was evaluated by the mean of cup-plate method. RESULTS: 13.6 mL of the extraction of sapindus saponin (crude drugs 0.01 g/mL) was purified with a column of macroporous adsorption resin (phi15 mm x H90 mm, dry weight 2.5 g) and washed with 3BV of distilled water, then eluted with 3BV of 30% ethanol and 3BV of 70% ethanol, most of saponins were collected in the 70% ethanol. CONCLUSION: With macroporous adsorption resin adsorbing and purifying, the elutive ratio of saponins was 93.8% and the purity reached 250.1%. So this process of applying macroporous adsorption resin to adsorb and purify saponins is feasible, and supplies reference to the purification of other types of saponin.

[Study on bioavilability of oxymatrine-phospholipid complex in rats].

OBJECTIVE: To study the plasma concentration-time curve, pharmacokinetic parameters and bioavilability of oxymatrine-phospholipid complex and to compare with oxymatrine in rats. METHOD: Rats were given oxymatrine-phospholipid 100 mg x kg(-1). Blood samples were collected at different times after oral administration. The internal standard was cimetidine. Protein in plasma was precipitated with merhanol and centrifuged at high speed. The supernatant was directly injected and assayed by CE method. The running buffer was 0.04 mol x L(-1) Tris-10 mmol x L(-1) sodium phosphate monobasic-40% isopropanol pH to 7.6 with phosphoric acid. The wavelength of detection was 205 nm. RESULT: The AUC of oxymatrine and oxymatrine-phospholipid complex were 4.52 mg x mL(-1) x h(-1) and 6.21 mg x mL(-1) x h(-1), respectively. The oxymatrine-phospholipid bioavailability enhanced 1.4 times. CONCLUSION: It is concluded that after oral administration of oxymatrine-phospholipid complex in rats the bioavailability of oxymatrine is increased greatly. This is mainly due to an obvious improvement of the lipophilic property of oxymatrine-phospholipid complex compared with oxymatrine material and an increase in gastrointestinal absorption.