Effects of Transcranial Ultrasound Stimulation on Blood Oxygen Metabolism and Brain Rhythms in Nitroglycerin-Induced Migraine Mice.

OBJECTIVES: In this study, we aimed to investigate the regulatory mechanism of transcranial ultrasound stimulation (TUS) on nitroglycerin-induced migraine in mice. MATERIALS AND METHODS: The experiment was divided into four groups, namely, the normal saline control group (n = 9), ultrasound stimulation control group (n = 6), nitroglycerin-induced migraine group (n = 9), and ultrasound stimulation group (n = 9). The behavior, blood oxygen metabolism, and brain rhythm distribution of the four groups were analyzed. RESULTS: We found that after TUS, the movement time and speed of mice with migraine are modulated to those of the control groups, and the number of head scratching and grooming events is significantly reduced. TUS increased the deoxygenated hemoglobin, and the power of the 4-to-40 Hz frequency band of local field potentials in the cortex of migraine mice. TUS also decreased the expression of plasma calcitonin gene-related peptide and cortical c-Fos protein. CONCLUSIONS: Ultrasound stimulation can regulate brain rhythm and blood oxygen metabolism and reduce migraine symptoms in mice. The regulatory mechanism may be related to reducing calcitonin gene-related peptide in blood vessels.

Low-intensity transcranial ultrasound stimulation modulates neural activities in mice under propofol anaesthesia.

BACKGROUND: Previous studies have reported that transcranial focused ultrasound stimulation can significantly decrease the time to emergence from intraperitoneal ketamine-xylazine anaesthesia in rats. However, how transcranial focused ultrasound stimulation modulates neural activity in anaesthetized rats is unclear. METHODS: In this study, to answer this question, we used low-intensity transcranial ultrasound stimulation (TUS) to stimulate the brain tissue of propofol-anaesthetized mice, recorded local field potentials (LFPs) in the mouse motor cortex and electromyography (EMG) signals from the mouse neck, and analysed the emergence and recovery time, mean absolute power, relative power and entropy of local field potentials. RESULTS: We found that the time to emergence from anaesthesia in the TUS group (20.3 ± 1.7 min) was significantly less than that in the Sham group (32 ± 2.6 min). We also found that compared with the Sham group, 20 min after low-intensity TUS during recovery from anaesthesia, (1) the absolute power of local field potentials in mice was significantly reduced in the [1-4 Hz] and [13-30 Hz] frequency bands and significantly increased in the [55-100 Hz], [100-140 Hz] and [140-200 Hz] frequency bands; (2) the relative power of local field potentials in mice was enhanced at [30-45 Hz], [100-140 Hz] and [140-200 Hz] frequency bands; (3) the entropy of local field potentials ([1-200 Hz]) was increased. CONCLUSION: These results demonstrate that low-intensity TUS can effectively modulate neural activities in both awake and anaesthetized mice and has a positive effect on recovery from propofol anaesthesia in mice.

Study on the relationship between hormone and Lp(a) in Chinese overweight/obese patients.

BACKGROUND: Obesity is a risk factor for metabolic diseases and often influences hormone change. Lipoprotein (a) (Lp(a)) is associated with various metabolic diseases, but there are few studies on the relationship between Lp(a) and hormones in obese patients. This study investigated the the relationship between Lp(a) and hormones in Chinese overweight/obese people. METHODS: A total of 410 overweight/obese patients (Body mass index (BMI) ≥ 25 kg/m2) were included and underwent sociodemographic data investigations and relevant clinical examinations. Lp(a) was analyzed by colorimetric enzymatic assays and hormone was measured with chemiluminescence immunoassay method. According to Lp(a) levels, they were categorized into 3 groups: the lower Lp(a) group (Lp(a) levels < 30 mg/dl), the moderate Lp(a) group (Lp(a) levels between 30 mg/dl and 120 mg/dl) and the higher Lp(a) group (Lp(a) levels > 120 mg/dl). The differences of hormone levels among the three groups were compared and the relationship between Lp(a) and hormones was analyzed by Spearman's rank correlation. RESULTS: The higher Lp(a) group had significantly lower testosterone (TES) levels compared with the lower and moderate Lp(a) groups in the case of gender, age and BMI matching. Lp(a) concentration was negatively correlated with TES levels in all participants and the negative association between Lp(a) and TES levels was also observed when the analysis was stratified by gender. Additionally, the TES was statistically related with Lp(a) levels in the multiple linear regression model (95% confidence interval: - 0.451 to - 0.079). CONCLUSIONS: TES levels was negatively associated with Lp(a) levels in Chinese overweight/obese patients.

Low-Intensity Pulsed Ultrasound Stimulation Inhibits Cortical Spreading Depression.

Cortical spreading depression (CSD), which is closely correlated with migraine aura, cerebral ischemia, seizure, and brain injury, is a spreading wave of neuronal and glial depolarization. The purpose of this study is to investigate whether low-intensity pulsed ultrasound stimulation (PUS) inhibits CSD by modulating neural activity and hemodynamics. Behavioral test, intrinsic signal optical imaging and western blot analysis were used for evaluating the inhibition effect of PUS on CSD in rat. We found that: 1) 30 min of PUS can significantly improve motor activity of rat with CSD. 2) Both 30 s and 30 min of PUS can significantly reduce count and propagation speed of CSD in rat and the inhibitory effect was enhanced with increase of ultrasound intensity. 3) 30 min of PUS significantly enhanced levels of brain-derived neurotrophic factor protein in brain tissue with CSD. These results suggest that PUS has the potential to treat brain disorders associated with CSD.

Parathyroid Hormone is Negatively Correlated with Glycated Hemoglobin in Newly Diagnosed Type 2 Diabetic Patients.

Objective: The growing evidence shows that parathyroid hormone (PTH) may affect glucose metabolism. However, the relationship between them is still controversial among diabetic patients. The current study aimed to investigate the relationship between PTH and glucose metabolism in the patients with newly diagnosed type 2 diabetes (T2D). Methods: A total of 532 participants, including 387 patients with newly diagnosed T2D and 145 healthy controls, were recruited in the present study. PTH and metabolic parameters were measured in all participants. Results: The PTH levels were significantly lower in the newly diagnosed T2D patients compared with the control group (35.10 (25.90, 47.20) vs. 47.15 (35.83, 58.65) pg/ml, P < 0.001). The T2D patients with a higher glycated hemoglobin (HbA1c) tertile had lower PTH levels than the patients with a lower HbA1c tertile (32.90 (24.85, 41.40) vs. 37.50 (26.10, 54.55) pg/ml, P < 0.001). Spearman correlation analysis showed that PTH was positively correlated with the body mass index (BMI), fasting insulin (FINS), homeostasis model assessment of ß-cell function (HOMA-ß), and homeostasis model assessment of insulin resistance (HOMA-IR) and negatively correlated with HbA1c, blood calcium (Ca), blood phosphorus (P), and 25-hydroxyvitamin D3 (25-OH-D3). Multiple linear regression analysis demonstrated that PTH was significantly associated with HbA1c (ß = -1.475, P=0.003) and HOMA-ß (ß = 0.090, P=0.001) after adjusting for age, sex, BMI, season, 25-OH-D3, Ca, and P. Conclusion: PTH was negatively correlated with HbA1c in the newly diagnosed T2D patients. Our results suggested that the PTH level within the reference range is related to islet ß-cell function and hyperglycemia.

Desynchronization of neuronal firing in multiparameter ultrasound stimulation.

Low-intensity transcranial ultrasound stimulation, a novel neuromodulation technique, that possesses the advantages of non-invasiveness, high penetration depth, and high spatial resolution, has achieved positive neuromodulation effects in animal studies. But the regulatory mechanism remains controversial. The intramembrane cavitation effect is considered one of the mechanisms for ultrasound neuromodulation. In this study, the modified equations of ultrasonic cavitation bubble dynamics were coupled with the dual-coupled neuron Hindmarsh-Rose model, small-world neural network model, and the Jansen-Rit neural mass model, which simulate simple coupled neurons, complex neuronal networks, and discharge signals in epileptic disorders respectively. The results demonstrated that ultrasound stimulation has an appreciable modulatory effect on neuronal firing desynchronization in Hindmarsh-Rose model and small-world neural network model. The desynchronization effect is related to the stimulation frequency and intensity. Furthermore, ultrasound stimulation has an inhibitory effect on epileptic seizures, and the effect is enhanced by increasing ultrasound frequency from 0.1-1.0 MHz. This is the first combination of ultrasonic intramembrane cavitation effect theory with neurons and neural network firing desynchronization, which can provide guidance of parametric and theories support for the studies of neurological diseases such as epilepsy and Parkinson's disease.

Serum Ferritin Levels Are Associated with Adipose Tissue Dysfunction-Related Indices in Obese Adults.

Iron overload is associated with type 2 diabetes and metabolic syndrome. However, little is known about the role of iron status on adipose tissue. We aimed to investigate the association of iron metabolism markers with adipose tissue dysfunction-related indices in obese individuals. A total of 226 obese adults with body mass index (BMI) ≥ 30 kg/m2 were recruited into the study. Hemoglobin, serum ferritin, iron, soluble transferrin receptor (sTfR), total iron-binding capacity (TIBC), transferrin saturation (TSAT), and other clinical parameters were measured. Adipose tissue dysfunction was assessed by adipose tissue insulin resistance (adipose-IR), visceral adiposity index (VAI), and lipid accumulation product (LAP) index. Serum ferritin levels, adipose-IR, and VAI progressively increased from class I to class III obesity and significantly higher in class III obesity. Correlation analysis suggested that only serum ferritin levels were positively correlated with adipose-IR (r = 0.284, P < 0.001), VAI (r = 0.209, P = 0.002), and LAP (r = 0.324, P < 0.001). Moreover, further logistic regression analysis revealed serum ferritin was significantly associated with elevated adipose-IR, VAI, and LAP. After adjustment for potential confounders, serum ferritin levels remained independently associated with elevated adipose-IR (OR = 1.004, 95% CI 1.000-1.009, P < 0.05) and VAI (OR = 1.005, 95% CI 1.001-1.009, P < 0.05). Serum ferritin was associated with elevated adipose-IR, VAI, and LAP, suggesting that ferritin could be an important early indicator for the risk of developing adipose tissue dysfunction in obese individuals.

Different Interactive Effects of Metformin and Acarbose With Dietary Macronutrient Intakes on Patients With Type 2 Diabetes Mellitus: Novel Findings From the MARCH Randomized Trial in China.

Antidiabetic oral agents and nutrition management are frequently used together as first-line therapies for type 2 diabetes mellitus (T2DM). However, less is known about their interaction. The interactive effect of two classic antidiabetic medications, namely, acarbose and metformin, with dietary intakes of macronutrients on glycemic control and cardiometabolic risk factors was investigated in the metformin and acarbose in Chinese as the initial hypoglycemic treatment (MARCH) randomized clinical trial. The patients with newly diagnosed T2DM from China were included in the trial. Participants were randomized to receive either metformin or acarbose monotherapy as the initial treatment, followed by a 24-week treatment phase, during which add-on therapy was used if necessary. Dietary intakes of carbohydrate, protein, fat, and total energy were calculated by a 24-h food diary recall method. Linear mixed-effect models combined with a subgroup analysis were used to investigate independent and interactive effects of drugs and diet on clinical outcomes. A data analysis was performed on 551 of the 788 patients randomly assigned to treatment groups. Metformin therapy was independently associated with higher triglycerides (TGs, ß = 0.471, P = 0.003), 2 h postprandial plasma glucose (2hPPG, ß = 0.381, P = 0.046) but lower low-density lipoprotein cholesterol (LDL-C, ß = -0.149, P = 0.013) compared with acarbose therapy. Higher carbohydrates and lower fat intakes were independently associated with poorer glycemic control, less weight loss, and greater insulin secretion. Higher total energy intake was also independently associated with higher fasting (ß = 0.0002, P = 0.001) and postprandial blood glucose (ß = 0.0004, P = 0.001). Interaction and subgroup analyses demonstrated that glucagon-like peptide-1 (GLP-1) was positively related to total energy (ß = 0.268, P = 0.033), carbohydrates intake, and insulin secretion (ß = 2,045.2, P = 0.003) only in the acarbose group, while systolic blood pressure (SBP) was negatively related to protein intake in the metformin group (ß = 23.21, P = 0.014). The results of this study showed that metformin and acarbose mainly exerted different interactive effects with dietary energy, carbohydrate, and protein intakes on GLP-1 secretion, insulin release, and SBP. The interaction between drug therapy and nutrition intervention in glycemia highlights the complexity of combination therapy.

Adipose Tissue Insulin Resistance Is Positively Associated With Serum Uric Acid Levels and Hyperuricemia in Northern Chinese Adults.

Objective: Adipose tissue plays a crucial role in serum uric acid (UA) metabolism, but the relative contribution of adipose tissue insulin resistance (IR) to serum UA levels and hyperuricemia have not explicitly been illustrated. Herein, we aimed to investigate the association between the adipose tissue insulin resistance index (Adipo-IR) and hyperuricemia in this cross-sectional study. The homeostasis model assessment of insulin resistance (HOMA-IR) index, another widely applied marker to determine systemic IR, was also explored. Methods: A total of 5821 adults were included in this study. The relationship between Adipo-IR or HOMA-IR and serum UA levels was assessed by multivariate linear regression. Binary logistic regression analyses were applied to determine the sex-specific association of the Adipo-IR tertiles and HOMA-IR tertiles with hyperuricemia. Participants were then divided into normal BMI (18.5 ≤ BMI < 24) and elevated BMI (BMI ≥ 24) groups for further analysis. Results: Both Adipo-IR and HOMA-IR were positively correlated with serum UA (P < 0.001). Compared with the lowest tertile, the risks of hyperuricemia increased across Adipo-IR tertiles (middle tertile: OR 1.52, 95%CI 1.24-1.88; highest tertile: OR 2.10, 95%CI 1.67-2.63) in men after full adjustment (P for trend < 0.001). In women, only the highest tertile (OR 2.09, 95%CI 1.52-2.87) was significantly associated with hyperuricemia. Those associations remained significant in participants with normal BMI status. As for HOMA-IR, only the highest tertile showed positive relationships with hyperuricemia in both genders after full adjustment (P for trend < 0.001). The association between HOMA-IR and hyperuricemia disappeared in men with normal BMI status. Conclusions: Adipo-IR was strongly associated with serum UA and hyperuricemia regardless of BMI classification. In men with normal BMI, Adipo-IR, rather than HOMA-IR, was closely associated with hyperuricemia. Altogether, our finding highlights a critical role of adipose tissue IR on serum UA metabolism and hyperuricemia.

Serum Metrnl levels are decreased in subjects with overweight or obesity and are independently associated with adverse lipid profile.

Background: Meteorin-like (Metrnl), a novel adipokine, is highly expressed in adipose tissue and has a beneficial effect on energy metabolism. However, data on circulating Metrnl levels in obesity are scarce and inconsistent. This study aimed to evaluate the serum levels of Metrnl in adults with obesity and its association with glucose and lipid metabolism. Methods: 182 subjects were included in the cross-sectional study. The participants were divided into three groups according to BMI: normal (n = 95), overweight (n = 46), and obesity (n = 41). Serum Metrnl concentrations were measured by enzyme-linked immunosorbent assay. Results: Serum Metrnl levels in overweight or obese subjects were significantly lower than in the normal group. Circulating Metrnl levels were negatively correlated with TG, TC, LDL-C, and sdLDL and positively correlated with HDL-C before and after adjusting for age, sex, BMI, diabetes, HOMA-IR, and eGFR (all P < 0.05). Furthermore, logistic regression analysis indicated that compared with the highest tertile, the lowest tertile of Metrnl levels were significantly associated with the presence of hyper-TG, hyper-TC, and Hyper-LDL after full adjustment (all P for trend < 0.05). Conclusions: Serum Metrnl levels were reduced in individuals with overweight or obesity and were independently associated with adverse lipid profile, suggesting that modifying circulating Metrnl levels may serve as a potential therapeutic target for atherogenic dyslipidemia.

Relatively Lower FT3 Levels Are Associated with Impaired Quality of Life in Levothyroxine-Treated Patients with Hashimoto Thyroiditis.

Objective: Patients with Hashimoto thyroiditis (HT) frequently have some complaints despite achieving euthyroidism after levothyroxine (LT4) treatment. This study aimed to investigate the relevant factors affecting the quality of life (QoL) in euthyroid HT patients after LT4 treatment. Methods: In this case-control study, 133 participants with HT were included. They were divided into two groups: 64 euthyroid HT subjects (control group) and 69 HT patients were rendered euthyroid by LT4 treatment (well-controlled group). QoL was measured with the Thyroid-Related Patient-Reported Outcome (ThyPRO-39) questionnaire. Results: Both study groups were well matched with respect to gender, age, BMI, euthyroidism, and thyroid antibodies (TPOAb and TGAb). Compared with the control group, the well-controlled group had lower FT3 (P < 0.01) levels. Of note, QoL was impaired on all scales in the well-controlled group. Moreover, ThyPRO-39 scores among the well-controlled group were significantly higher (worse) than the control group in all scales. Regarding the composite scale, its score was related to FT3 (r = -0.176, P=0.043) but not to FT4 and TSH levels. Further logistic regression analysis revealed FT3 was significantly associated with elevated composite QoL [0.128 (0.029-0.577), P < 0.01] after adjustment of potential confounders. Conclusion: Relatively lower FT3 concentrations, even within the normal reference range, were related to impaired QoL in HT patients treated with LT4. This finding supports the great value of FT3 in clinical decision-making on dose adequacy.

Obese patients with higher TSH levels had an obvious metabolic improvement after bariatric surgery.

OBJECTIVE: Bariatric surgery has become the most effective treatment for morbid obesity. Increasing evidence showed that bariatric surgery can alleviate insulin resistance and influence thyroid function. This study aimed to investigate the relationship between changes in thyroid function and adipose tissue insulin resistance (adipo-IR) after bariatric surgery. METHODS: A total of 287 non-diabetic participants with regular thyroid function were recruited and divided into the lean, overweight and obese groups. Among them, 50 morbidly obese patients submitted to bariatric surgery. RESULTS: The obese group had a higher level of adipo-IR, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), FT3/free thyroxine (FT4) and metabolism disorders than the lean and overweight groups. BMI was correlated with TSH, FT3, FT3/FT4 and adipo-IR (r = 0.309, 0.315, 0.322 and 0.651, respectively, all P < 0.001). Adipo-IR was significantly correlated with TSH (r = 0.402, P < 0.001), FT3 (r = 0.309, P < 0.001), and FT3/FT4 (r = 0.228, P < 0.05). Bariatric surgery resulted in a sharp decline in BMI, adipo-IR, TSH, FT3 and FT3/FT4 levels, meanwhile, metabolic disorders improved. The decrease in BMI after bariatric surgery was significantly correlated with reductions in adipo-IR (r = 0.577, P < 0.001) and TSH (r = 0.401, P = 0.005). Interestingly, the fasting blood glucose, fasting insulin, adipo-IR and TSH in the higher TSH group decreased more remarkably than in the lower TSH group. CONCLUSION: Obese individuals with higher TSH levels had an obvious metabolic improvement after bariatric surgery.

The relationship of plasma fibrinogen with clinicopathological stages and tumor markers in patients with non-small cell lung cancer.

Numerous studies have shown that the blood of cancer patients are generally in hypercoagulable statement. The aim of the present research is to study the relationships of plasma fibrinogen (Fbg) levels with clinicopathological stages (CS) and tumor markers of non-small cell lung cancer (NSCLC).Baseline information, plasma Fbg levels, CS, and expression level of tumor markers were collected from medical records retrospectively. Unitary linear regression was used to analyze the relationships between continuous variables and Fbg, and multiple linear regression was used to analyze the relationships between categorical variables and Fbg. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (Version 4) for NSCLC were adopted to evaluate CS.A total of 652 NSCLC patients were included. Compared with the females, male patients had higher mean plasma Fbg levels (P < .001). The later the N stages (P = .002), M stages (P = .002), and CS (P = .001) were, the higher the average plasma Fbg levels were. The levels of squamous cell carcinoma antigen (P = .001), carbohydrate antigen 125 (P = .041), and neuron-specific enolase (P < .001) were positively correlated with plasma Fbg concentration. The plasma level of Fbg in lung adenocarcinoma patients (P < .001) was the lowest, while that of lung squamous cell carcinoma patients (P < .001) was the highest in NSCLC patients.The plasma Fbg concentration is related to gender, CS, and tumor markers in patients with NSCLC.