Objective study of the facial parameters of observations in patients with type 2 diabetes mellitus by machine learning.

Background: A predictive model of facial feature data was established by machine learning to screen the objective parameters of risk factors of facial morphological features of type 2 diabetes mellitus (T2DM) following the theory of traditional Chinese medicine (TCM). In TCM, a facial inspection is an important way to diagnose patients. Doctors can judge the health status of their patients by observing their facial features. However, the lack of description of the objective parameters and quantitative indicators hinders the development of TCM testing research. Methods: In this study, the following diagnostic criteria for diabetes developed by the World Health Organization (WHO) in 1999 were used to determine the inclusion and exclusion criteria for T2DM and non-T2DM. T2DM patients and control participants were enrolled in the study, and their facial images were collected. In this study, two facial inspection risk-factor models were constructed, including the "lambda.min" and "lambda.1se" model. Results: A total of 81 key points in the facial images were screened, and 18 facial morphological parameters were measured. The least absolute shrinkage and selection operator (LASSO) regression model was used to construct T2DM facial inspection risk-factor models. The area under the curves (AUCs) of the "lambda.min" model and the "lambda.1se" model were 0.799 and 0.776, respectively. The predictive efficiency of the two T2DM risk models selected by the LASSO regression model was relatively high. Among the eight parameters, the width of the jaw was the most important of the defined facial features. According to the receiver operating characteristic (ROC) curve analysis of the two prediction models constructed, the two models had good predictive efficiency for T2DM. The AUCs of the two models were 0.695 and 0.682, respectively. And the reproducibility is good. The prediction model was available, which showed that the objective parameters of the facial features recognized by machine learning have a certain value in the automatic prediction of T2DM. Conclusions: The influence of facial features is physical factor. Thus, the objective parameters of facial features should be specific to differential diagnosis of T2DM.

Mechanism of Fuzheng Kang'ai Formula Regulating Tumor Microenvironment in Non-Small Cell Lung Cancer.

OBJECTIVE: To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula (, FZKA) on tumor microenvironment (TME). METHODS: CIBERSORTx was used for analysis of TME. Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas (TCGA) was employed to identify the differential expression genes (DEGs) between tumor and paracancerous tissues in lung adenocarcinoma (LUAD) from TCGA-LUAD. Additionally, DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression. The core targets of FZKA were analyzed in lung adenocarcinoma TME. Protein-protein interaction database was employed to predict down-stream of target. Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549, H1299 and PC9 cell lines. RESULTS: The active and resting mast cells were significantly associated with prognosis of LUAD (P<0.05). Of the targets, CCNA2 as an important target of FZKA (hazard ratio=1.41, 95% confidential interval: 1.01-2.01, P<0.05) was a prognostic target and significantly associated with mast cells. CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state. BCL1L2, ACTL6A and ITGAV were down-stream of CCNA2, which were validated by qRT-PCR in A549 cell. CONCLUSION: FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.

Aerobic Exercise Attenuates Pressure Overload-Induced Cardiac Dysfunction through Promoting Skeletal Muscle Microcirculation and Increasing Muscle Mass.

BACKGROUND: Aerobic exercise has been proven to have a positive effect on cardiac function after hypertension; however, the mechanism is not entirely clarified. Skeletal muscle mass and microcirculation are closely associated with blood pressure and cardiac function. OBJECTIVE: This study was designed to investigate the effects of aerobic exercise on the skeletal muscle capillary and muscle mass, to explore the possible mechanisms involved in exercise-induced mitigation of cardiac dysfunction in pressure overload mice. METHODS: In this study, 60 BALB/C mice aged 8 weeks were randomly divided into 3 groups: control (CON), TAC, and TAC plus exercise (TAE) group and utilized transverse aortic constriction (TAC) to establish hypertensive model; meanwhile, treadmill training is used for aerobic exercise. After 5 days of recovery, mice in the TAE group were subjected to 10-week aerobic exercise. Carotid pressure and cardiac function were examined before mice were executed by Millar catheter and ultrasound, respectively. Muscle mass of gastrocnemius was weighed; cross-sectional area and the number of capillaries of gastrocnemius were detected by HE and immunohistochemistry, respectively. The mRNA and protein levels of VEGF in skeletal muscle were determined by RT-PCR and western blot, respectively. RESULTS: We found that ① 10-week aerobic exercise counteracted hypertension and attenuated cardiac dysfunction in TAC-induced hypertensive mice; ② TAC decreased muscle mass of gastrocnemius and resulted in muscle atrophy, while 10-week aerobic exercise could reserve transverse aortic constriction-induced the decline of muscle mass and muscle atrophy; and ③ TAC reduced the number of capillaries and the protein level of VEGF in gastrocnemius, whereas 10-week aerobic exercise augmented the number of capillaries, the mRNA and protein levels of VEGF in mice were subjected to TAC surgery. CONCLUSIONS: This study indicates that 10-week aerobic exercise might fulfill its blood pressure-lowering effect via improving skeletal muscle microcirculation and increasing muscle mass.

Study on the anti-tumor mechanism related to immune microenvironment of Bombyx Batryticatus on viral and non-viral infections of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. Most previous studies on anti-HCC effects of traditional Chinese medicines (TCM) have focused on the mechanism of direct action and few researchers considered that TCM can inhibit tumor progression and improve prognosis of HCC patients through regulating tumor microenvironment (TME). In this study, network pharmacology combined bioinformatics methods were employed to analysis mechanism of Bombyx batryticatus (B. batryticatus, one of the most frequently used traditional Chinese animal medicines, has been used in some Asian countries for centuries as an anticancer agent, anti-inflammatory agent, and antioxidant.) in regulating TME of HCC. The results showed that 24 core targets and 2 compounds were identified from overlapping between differential expression genes related to HCC in the cancer genome atlas (TCGA) database and targets of B. batryticatus in TCMSP database. For further analyzing the role of TME heterogeneity of HCC on anti-HCC mechanism of B. batryticatus, the correlation of core targets related with overall survival of HCC with TME cells in hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (VIR) and non-hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (NVIR) were calculated, respectively. The results showed that AKR1C3, SPP1 were significantly related with macrophages in VIR and other targets including NR1I2, CYP1A2 and CYP3A4 were significantly associated with macrophages in NVIR; the target protein AKR1C3 was significantly negative correlated with macrophages M1 in VIR (cor=-0.35, P-value<0.001) and the correlation between AKR1C3 and macrophages M1 was poor in NVIR group (cor = 0.064, P-value = 0.36). Additionally, survival curve of AKR1C3 showed that poor prognosis in VIR group can be related to high level of AKR1C3 (HR = 2.32, 95 % CI: 1.18-4.56, P-value = 0.012), and no signified gene can be found in NVIR group (P-value>0.05). In conclusion, the molecular mechanism of anti-HCC of B. batryticatus can be related to the tumor microenvironment to some extent. B. batryticatus may exert its anti-cancer effects and improve prognosis of patients by regulating macrophages M1 in VIR and NVIR through acting on different targets.

Tongxinluo inhibits oxidized low-density lipoprotein-induced maturation of human dendritic cells via activating peroxisome proliferator-activated receptor gamma pathway.

TongXinLuo (TXL) is a traditional Chinese herbal medicine with multiple vasoprotective activities. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. The purpose of this study was to determine the effect and possible mechanisms of TXL on oxidized low-density lipoprotein (OX-LDL)-induced maturation and immune function of DCs. Human monocyte-derived DCs were incubated with TXL or ciglitazone and were subsequently stimulated with OX-LDL to induce maturation. Similar to ciglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, TXL could significantly reduce the maturation-associated markers induced by OX-LDL, such as CD40, CD86, CD1a, and human leukocyte antigen-DR; improved the endocytotic function; and decreased secretions of cytokine interleukin-12 and tumor necrosis factor alpha. These inhibitory effects of TXL could be partly reversed by silencing the expression of PPAR gamma in DCs. In conclusion, TXL could inhibit OX-LDL-induced maturation of DCs through activating PPAR gamma pathway.

Inhibiting effects of total saponins of panax ginseng on immune maturation of dendritic cells induced by oxidized-low density lipoprotein.

Total saponins of panax ginseng (TSPG) are the major active components in panax ginseng. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. The purpose of this study was to determine the effect and possible mechanisms of TSPG on the maturation and immune function of DCs. Compared with those untreated, the DCs pre-treated with TSPG and then induced by oxidized-LDL exhibited a significantly lower expression of the maturation-associated markers of CD40, CD86, HLA-DR, and CD1a, together with an increased endocytosic function as well as decreased secretions of cytokine. However, silencing the expression of PPARgamma in DCs, the inhibitory effect of TSPG on the maturation DCs was significantly reduced. In conclusion, TSPG could inhibit the maturation of DCs induced by oxidized-LDL which suggests beneficial effects on atherosclerosis and this effect was partly dependent on the PPARgamma pathway at least.

[Protective effect of tongxinluo superfines on angiotensin II caused renal injury in rat].

OBJECTIVE: To explore the renal protective effect of Tongxinluo (TXL) and its mechanism of action. METHODS: Eight-week old SD rats were divided into the sham-operated group (A), the model group (B) and the TXL group, 6 rats in each group. Angiotensin II (Ang II) was administered slowly (200 ng/kg per min) to rats in group B and C via subcutaneously embedded osmotic pump to make them stimulative model of renal injury, while to rats in group A, pump embedding with saline infusion. After modeling, TXL was given to group C by gastric perfusion in dosage of 0.8 g/kg per day. And the following indexes were observed 14 days later: configuration of renal arterial endothelium by transmission electron microscope; pathologic figure of kidney with HE stain; renal apoptosis by TUNEL; expression of p53 and p22phox by RT-PCR;and level of reactive oxygen species (ROS) in kidney. RESULTS: Different degree of congestion, swelling, denudation of endothelial cell in renal arterial endothelial cell; glomerular matrix proliferation and partial glomerular atrophy with tendency of fibrosis; increased renal parenchymal apoptosis; enhanced expression of p53 and p22phox; and elevated ROS were found in model animals. All the above-mentioned abnormalities, including glomerular injury, renal cell apoptosis, as well as the increased p53, p22phox expressions and ROS production were all alleviated in group C after TXL treatment. CONCLUSION: TXL could protect renal against Ang II injury, and it may be realized by inhibiting NADPH-ROS/p53 pathways and suppressing cell apoptosis in renal parenchyma.