[Clinical features and risk factors of metabolic syndrome in adult hypopituitary patients].

Objective: To investigate the clinical features and risk factors of metabolic syndrome (MS) in adult hypopituitary patients (HP). Methods: Patients diagnosed with HP in the outpatient or inpatient department of the endocrinology department in West China Hospital from January,2012 to December,2019 were selected as the experimental group (HP group), and patients with normal pituitary function treated for saddle lesions were selected as the control group. HP patients with or without MS were divided into MS group and non-MS group HP patients were divided into four groups according to the level of growth hormone by the quartile method (GH>0.35 µg/L、0.13 µg/L0.35 µg/L、0.13 µg/L

[Effect of peripheral hyperinsulinemia on assessment of pharmacokinetics and pharmacodynamics of insulin preparations in euglycemic clamp].

Objective: To evaluate the effect of peripheral hyperinsulinemia on assessment of pharmacokinetics (PK) and pharmacodynamics (PD) of insulin preparations in euglycemic clamp. Method: A total of 40 healthy male volunteers aged 18-45 years old in West China Hospital between 2015 and 2017 were divided into euglycemic-hyperinsulinaemic clamp (A) group and euglycemic clamp (B) group. Humulin R (0.2 U/kg) was given subcutaneously at steady state of clamp after infusion of short-acting insulin in A group while in B group Humulin R was given subcutaneously without establishment of artificial hyperinsulinemia. The blood glucose was maintained within target range during the whole clamp. Result: Maximum insulin concentration [(667±141) pmol/L vs (267±68) pmol/L, P<0.01] and area under curve (AUC) of insulin concentration [(152±32) nmol·L(-1)·min vs (57±7) nmol·L(-1)·min, P<0.01] in A group were higher while maximum glucose infusion rate (GIR) [(3.70±0.70) mg·kg(-1)·min(-1) vs (7.66±2.11) mg·kg(-1)·min(-1), P<0.01] and AUC of GIR [(931±272) mg/kg vs (1 920±452) mg/kg, P<0.01] were lower compared to B group. The serum C-peptide levels were lower in both groups after administration of insulin compared with baseline. Conclusion: It is not necessary applying euglycemic-hyperinsulinaemic clamp to evaluate the PK/PD of insulin preparations, which may overestimate the PKparameters and underestimate the PD parameters of insulin preparations.

Sculpting tumor microenvironment with immune system: from immunometabolism to immunoediting.

Cancer immunotherapy unleashing the power of host immunity on eliminating cancer cells represents a critical advance in cancer treatment; however, effective anti-tumor responses are largely dampened by the immunosuppressive tumor microenvironment (TME). Emerging studies have revealed that physiological features in the TME, including glucose deprivation, hypoxia and low pH, established by the metabolically dysregulated cancer cells restrict anti-tumor immunity by impeding the metabolic fitness of tumor-infiltrating cytotoxic CD8+ T cells and natural killer (NK) cells. Furthermore, infiltrating immunomodulatory cells with different metabolic preferences also facilitate the establishment of the immunosuppressive TME. Therefore, deciphering the metabolic cross-talk between immune cells and cancer cells in the TME and elucidating the impact of this process during tumorigenesis are needed to harness anti-tumor immunity more effectively. Herein, we summarize the immunosuppressive features of TME and how these features impair anti-tumor immunity. Moreover, we postulate how immune cells may be involved in shaping the metabolic features of cancer cells and discuss how we might improve the anti-tumor functions of tumor-specific T cells by rewiring their metabolic regulations.

OXTR and ZEB1 expression before and after progesterone dosing in pregnant women with threatened premature labor.

OBJECTIVE: To investigate changes in the peripheral blood mRNA levels of oxytocin receptor (OXTR) and Zinc finger E-box-binding homeobox 1 (ZEB1) before and after progesterone dosing in pregnant women with threatened premature labor. PATIENTS AND METHODS: Blood samples were collected from 30 healthy pregnant women with 28- to 33+6-week gestational age and singleton pregnancy (group A) and from 30 pregnant women with singleton pregnancy and threatened premature labor before and 48 hours after progesterone dosing (groups B and C, respectively) for quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assay to assess the OXTR and ZEB1 mRNA levels. RESULTS: The OXTR mRNA level was higher in the group B than in the groups A and C, and the ZEB1 mRNA level was lower in the group B than in the groups A and C. Notably, no significant difference was found in the mRNA level of OXTR or ZEB1 between group A and group C. CONCLUSIONS: The peripheral blood mRNA level of OXTR was increased, and that of ZEB1 was decreased in pregnant women with threatened premature labor. Progesterone helped to maintain pregnancy by readjusting the mRNA levels of OXTR and ZEB1.

Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK-eNOS Pathway.

OBJECTIVE: Hypoadiponectinemia has been proved to be closely related to endothelial dysfunction in peripheral arteries and is thought to be an independent risk factor for cardiovascular disease. The objective of this study was to investigate whether adiponectin might independently improve endothelial dysfunction in aorta isolated from high-fat-diet-induced obese. Sprague-Dawley rat and to study the mechanism involved. RESEARCH DESIGN AND SUBJECTS: Male Sprague-Dawley rats were fed with a regular or a high-fat diet for 6 weeks. The aorta was isolated, and vascular segments were incubated with vehicle or the globular adiponectin (globular domain (gAD); 2 mg ml(-1)) for 2 h. The effect of gAD on endothelial function and nitric oxide (NO) production was determined. Human aortic endothelial cells in primary culture were treated with vehicle or gAD (4 mg ml(-1)). The effect of gAD on the level of phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177, AMPK at Thr176 and Akt at Ser473 in endothelial cells were determined. RESULTS: Severe endothelial dysfunction was observed in high-fat diet fed rat aortic segments. After gAd incubation, the endothelium-dependent relaxation was partly improved and total production of nitric oxide as result of enhanced eNOS activity was also increased. In the cultured endothelial cell line HUVEC, globular adiponectin increased the activity of eNOS through activating AMPK by stimulating its phosphorylation at Thr176 but not Akt. CONCLUSION: The demonstration in the current study that adiponectin reverses endothelial dysfunction through increasing NO production by eNOS phosphorylation, and decreasing NO inactivation by blocking superoxide production provides a new direction in the prevention of vascular injury in the obesity population.

Mutational analysis of the fractalkine chemokine domain. Basic amino acid residues differentially contribute to CX3CR1 binding, signaling, and cell adhesion.

Fractalkine (FKN/CX3CL1) is a unique member of the chemokine gene family and contains a chemokine domain (CD), a mucin-like stalk, a single transmembrane region, and a short intracellular C terminus. This structural distinction affords FKN the property of mediating capture and firm adhesion of FKN receptor (CX3CR1)-expressing cells under physiological flow conditions. Shed forms of FKN also exist, and these promote chemotaxis of CX3CR1-expressing leukocytes. The goal of the present study was to identify specific residues within the FKN-CD critical for FKN-CX3CR1 interactions. Two residues were identified in the FKN-CD, namely Lys-7 and Arg-47, that are important determinants in mediating an FKN-CX3CR1 interaction. FKN-K7A and FKN-R47A mutants exhibited 30-60-fold decreases in affinity for CX3CR1 and failed to arrest efficiently CX3CR1-expressing cells under physiological flow conditions. However, these mutants had differential effects on chemotaxis of CX3CR1-expressing cells. The FKN-K7A mutant acted as an equipotent partial agonist, whereas the FKN-R47A mutant had marked decreased potency and efficacy in measures of chemotactic activity. These data identify specific structural features of the FKN-CD that are important in interactions with CX3CR1 including steady state binding, signaling, and firm adhesion of CX3CR1-expressing cells.

[Changes of dynamic ECG before, during, and after parabolic flight].

Objective. To study the characteristics of pilots' electrocardiogram during parabolic flight. Method. Dynamic electrocardiogram (DCG, CM1 and CM5 bipolar leads) were recorded in 13 pilots before, during and after parabolic flights. Result. Preflight and postflight values of heart rate (HR) and cardiac rhythm were essentially the same in all cases, but HR increased to a higher level of 86.0 +/- 7.3 bpm with maximum of 137.0 +/- 12.2 bpm, and minimum of 57.7 +/- 6.6 bpm during parabolic flights. During flights, one pilot's cardiac rhythm changed slightly and in another pilot T wave became inverted. In other two pilots, ST segments shifted downward more than 0.1 mV transiently. All these pilots showed negative result in maximal exercise on the ground. Conclusion. DCG could be used to evaluate the changes of cardiac electric activity during the whole parabolic flight.

[Relation of pilots symptoms with some physiological parameters under vestibular stimulus].

OBJECTIVE: To investigate the relation of vestibular stimulus induced symptoms to electrogastrogram (EGG), electronystagmogram (ENG), acupoint potential (AP), skin temperature (ST) heart rate variability (HRV) and content of urine hormones. METHOD: The physiological parameters were recorded before, during and after vestibular stimuli. Graybiel's scoring standard was used, and progressive regression analysis of symptoms and physiological parameters were made. RESULT: The regression equations were obtained from data before, during and after the stimuli. CONCLUSION: Three regression equations might be used.

Effect of Konjac food on blood glucose level in patients with diabetes.

Seventy-two type II diabetic subjects were given Konjac food for 65 days. The data analyzed by multiple F test indicate that the fasting blood glucose (FBG) and the 2-h postprandial blood glucose (PBG) on the 30th and the 65th days after the food was ingested were significantly reduced (P = 0.001, P less than 0.001, respectively), as was the glycosylated hemoglobin level at the end of the trial (P less than 0.05). The final FBG and PBG of the subjects with initial FBG-O greater than 200 mg% decreased on the average by 51.8 and 84.6 mg%, respectively; those with FBG-O 150-200 mg% decreased by 24.1 and 68.7 mg%; and those with FBG-O less than 150 mg% decreased by 4.8 and 21.4 mg%. No significant changes in blood lipid indexes were observed, except that the triglyceride values of subjects with hypertriglyceridemia (greater than 200 mg%) significantly decreased by 118.7 mg%. It was concluded that Konjac food is very useful in the prevention and treatment of hyperglycemia.