[The association between baseline TPOAb and/or TgAb positivity and thyroid immune-related adverse events in patients with malignancies following treatment with immune checkpoint inhibitors].

Objective: To investigate the association between positive anti-thyroid peroxidase antibody (TPOAb) and/or anti-thyroglobulin antibody (TgAb) and the occurrence of thyroid immune-related adverse events (irAEs) in patients with malignant tumors who treated with immune checkpoint inhibitors (ICIs). Methods: A case-control study. A total of 116 patients with malignant tumor who received ICIs treatment and underwent thyroid function evaluation at Peking Union Medical College Hospital from January 2017 to April 2023 were enrolled retrospectively, including 77 males and 39 females, with a median age of (M(Q1, Q3)) 63.0 (55.0, 70.0) years. The patients were divided into the euthyroid group (n=58) and the thyroid irAEs group (n=58) according to whether thyroid irAEs occurred after ICIs treatment. The clinical characteristics and baseline anti-thyroid antibodies associated with the occurrence of thyroid irAEs after ICIs treatment in patients with malignant tumors were evaluated. Variables with statistical significance in univariate analysis were included in multivariate logistic regression model to analyze the risk factors for thyroid irAEs in patients with malignant tumors who received ICIs treatment. Results: In irAEs group, therewore 4 (3.4%) cases of clinical thyrotoxicosis, 23(19.8%) cases of subclinical thyrotoxicosis, 23 (19.8%) cases of clinical hypothyroidism, and 8(6.9%) cases of subclinical hypothyroidism. The positive rate of anti-thyroid antibodies at baseline in the thyrioid irAEs group was higher than that in the euthyroid group［16/58（27.6%）vs 3/58（5.2%），P=0.001］. After at least one course of ICIs treatment, the incidence of thyroid irAEs in patients with positive anti-thyroid antibodies at baseline was 84.2% (16/19), whereas it was 43.3% (42/97) in patients with negative anti-thyroid antibodies(P=0.001). Univariate logistic regression analysis showed that gender (OR=2.812, 95%CI:1.257-6.293), baseline thyroid autoantibodies were positive (OR=6.984, 95%CI: 1.909-25.547), baseline TgAb positivity (OR=8.909, 95%CI: 1.923-41.280), and baseline TPOAb positivity (OR=7.304, 95%CI: 1.555-34.308) were associated with thyroid irAEs (all P<0.05). Multivariate logistic regression analysis indicated that baseline TgAb positivity (OR=7.637, 95%CI: 1.617-36.072) was a risk factor for thyroid irAEs (P=0.01). Conclusions: The incidence of thyroid irAEs is higher in patients who are positive for baseline TPOAb and/or TgAb compared to those who are negative for TPOAb and TgAb. Patients with positive TgAb at baseline are at high risk of developing thyroid irAEs.

[Advances in clinical prediction scores for prognosis of coronavirus disease-2019].

Coronavirus Disease-2019 (COVID-19) has been a major public health issue all over the world, placing a significant burden on available healthcare resources. The most common types of COVID-19 are the mild and common forms. Although the proportion of the severe-critical types is smaller, the rate of death is significantly higher and the medical resources required tend to be greater. Thus, a variety of scores based on other disease and COVID-19 were used to assess the risk of poor prognosis on the COVID-19, including the common scores for community-acquired pneumonia, sepsis and viral pneumonia. Unfortunately, the above scores often lacked an adequate description of the applicable population or were at high risk of bias with unknown applicability. Therefore, the article summarized the existing scores, aiming to provide a reference for clinical prognostic risk assessment.

[Etiology and clinical features of primary adrenal insufficiency].

Objective: To summarize the etiology of primary adrenal insufficiency (PAI) and analyze its clinical features. Methods: A retrospective analysis was performed in the Department of Endocrinology, Peking Union Medical College Hospital from October 1981 to June 2019. Patients with PAI as the first symptom were enrolled. The etiology of PAI was analyzed and the clinical characteristics was also summarized. Results: A total of 131 patients with PAI were enrolled, including 87 males and 44 females (57 adolescents, and 74 adults). The age ranged from 0 to 73 years. The primary cause of PAI in adolescents was genetic defects (52.6%, 30/57), in which congenital adrenal dysplasia caused by DAX1 gene deficiency accounted for 50.0% (15/30), followed by autoimmunity (22.8%, 13/57). The primary cause of adult PAI was infection (58.1%, 43/74), of which tuberculosis accounted for the majority (93.0%, 40/43), and autoimmune adrenalitis accounted for 19.0% (14/74). Compared with the tuberculosis group, female patients were more common, and the onset age was younger, the plasma cortisol, serum sodium, fasting blood glucose, creatinine and aldosterone were lower (all P<0.05), and serum potassium and renin levels were higher in the autoimmune adrenalitis group (both P<0.05). Conclusions: In the current study, the proportion of PAI caused by infection in the adult group was higher than that in the adolescent group. The most common cause of adult PAI was tuberculosis infection. The most common cause of childhood PAI was genetic defects. Autoimmune damage to the adrenal glands may be more severe than tuberculosis infection.

LncRNA SNHG7 is an Oncogenic Biomarker Interacting with MicroRNA-193b in Colon Carcinogenesis.

BACKGROUND: The expression and significance of small nucleolar RNA host gene 7 (SNHG7) in early-stage colon carcinogenesis remains unclear. METHODS: The level of SNHG7 and microRNA-193b (miR-193b) was detected by qRT-PCR in colon tumor tissues and cells. The interaction of SNHG7 and miR-193b and the influence of SNHG7 silencing on colon tumor cells was evaluated. RESULTS: Stepwise upregulated SNHG7 in colon advanced adenomas and early-stage cancer negatively correlates with miR-193b level, the direct interaction was confirmed in vitro. SNHG7 silencing in HT29 cells decreased proliferation and promoted apoptosis by inhibiting K-ras/ERK/cyclinD1. CONCLUSIONS: SNHG7 is an oncogenic biomarker in colon carcinogenesis. The effect may be mediated by interaction with miR-193b.

Zinc-alpha2-glycoprotein is involved in regulation of body weight through inhibition of lipogenic enzymes in adipose tissue.

CONTEXT: Zinc-alpha2-glycoprotein (ZAG) was found to influence lipolysis in adipose tissue and has recently been proposed as a candidate factor in the regulation of body weight. OBJECTIVE: To elucidate the association of serum ZAG level with body weight and percentage of body fat in normal, obese subjects and high-fat diet (HFD)-induced obese mice. DESIGN: The relationship between serum ZAG and obesity-related parameters was studied in 44 human subjects and 36 mice fed standard food and HFD. Furthermore, the effects of ZAG overexpression on adipose tissue of mice was also evaluated by using a liposome transfection method. RESULTS: Serum ZAG level was significantly lower in obese patients and obese mice in comparison to that in people and mice with normal weight. The further statistical analysis demonstrated that ZAG level was negatively correlated with body weight (r=-0.62, P<0.001), body mass index (r=-0.64, P<0.001), waist circumference(r=-0.68, P<0.001), hip circumference (r=-0.60, P<0.001), percentage of body fat (r=-0.52, P=0.03) and fat mass(r=-0.59, P=0.01) in human subjects after adjustment for age and sex. Furthermore, ZAG overexpression in mice reduced body weight and the percentage of epididymal fat. The decreased FAS, ACC1 and DGAT mRNA and the increased HSL mRNA were also observed in epididymal adipose tissue in ZAG overexpression mice. CONCLUSION: ZAG is closely linked to obesity. Serum ZAG level is inversely associated with body weight and percentage of body fat. The action of ZAG is associated with downregulated lipogenic enzymes and upregulated lipolytic enzyme expressions in adipose tissue of mice.

Involvement of vanilloid receptors in heat stress-induced delayed protection against myocardial ischemia-reperfusion injury.

Sprague-Dawley rats were pretreated with whole body hyperthermia (rectal 42 degrees C) for 15 min, 24 h before the experiments, and then the left main coronary artery of rat hearts was subjected to a 60 min occlusion followed by 3 h reperfusion. Myocardium injury degree was evaluated by measurement of infarct size and serum creatine kinase (CK) activity. Plasma concentrations of calcitonin gene-related peptide (CGRP), and the expression of alpha- and beta-CGRP mRNA in dorsal root ganglia were determined by radioimmunoassay and semi-quantitative reverse-transcription polymerase chain reaction, respectively. Hyperthermia treatment significantly reduced infarct size and CK release concomitantly with a dramatic increase in plasma concentrations of CGRP and the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, which was completely abolished by pretreatment with capsazepine (38 mg/kg, s.c.), a competitive vanilloid receptor 1 antagonist. These results suggests that vanilloid receptor 1 on capsaicin-sensitive sensory nerves plays an important role in the modulation of the delayed cardioprotection induced by heat stress in rats.

Endothelium-dependent vasorelaxation and the expression of calcitonin gene-related peptide in aged rats.

To explore the age-related change in endothelium-dependent vasorelaxation, plasma concentrations and the expression of calcitonin gene-related peptide (CGRP) as well as serum concentrations of asymmetry dimethylarginine (ADMA), male Sprague-Dawley rats, aged 6 and 24 months were tested. The level of ADMA and CGRP in blood, and CGRP mRNA in dorsal root ganglia (DRG) were determined by high-performance liquid chromatography (HPLC), radioimmunoassay or semi-quantitative reverse-transcription polymerase chain reaction, respectively. Vasodilator responses to cumulative concentrations of acetylcholine (ACh) (3 x 10(-9) - 3 x 10(-7)M) and CGRP (3 x 10(-10) - 3 x 10(-8)M) were tested at the plateau of contraction in aortas rings. Vasodilator responses to ACh or CGRP at 24 months of age were decreased compared with 6 months. The serum concentration of ADMA at 24 months of age was significantly increased compared with 6 months, while both plasma concentrations of CGRP and the expressions of alpha- and beta-CGRP mRNA were unchanged at two age groups. The results suggest that endothelium-dependent relaxation, but not concentrations and the expressions of CGRP, is decreased in aged rats, and the decrease in endothelium dependence of vasodilator response to CGRP may be related to the elevation of endogenous ADMA.

2'-C-branched ribonucleosides. 2. Synthesis of 2'-C-beta-trifluoromethyl pyrimidine ribonucleosides.

[structure: see text]. The first synthesis of 2'-C-beta-trifluoromethyl pyrimidine ribonucleosides is described. 1,2,3,5-Tetra-O-benzoyl-2-C-beta-trifluoromethyl-alpha-D-ribofuranose (3) is prepared from 1,3,5-tri-O-benzoyl-alpha-D-ribofuranose (1) in three steps and converted to 3,5-di-O-benzoyl-2-C-beta-trifluoromethyl-alpha-D-1-ribofuranosyl bromide (5). The 1-bromo derivative (5) is found to be a powerful reaction intermediate for the synthesis of ribonucleosides. The reaction of silylated pyrimidines with (5) in the presence of HgO/HgBr2 affords exclusively the beta-anomers (6-8). Deprotection of (6-8) with ammonia in methanol yields the 2'-C-beta-trifluoromethyl nucleosides (9-11).

Antithrombotic effects of low-molecular-weight heparin calcium (LMWH-Ca) in experimental models.

The antithrombotic activity of low-molecular-weight heparin calcium (LMWH-Ca) was studied in venous and arterial thrombosis models, arterial thrombosis model in rats, arterio-venous shunt model and venous thrombosis model in rabbits. The data showed that LMWH-Ca reduced thrombus formation in a dose-dependent manner. It suggests that LMWH-Ca is a potent antithrombotic agent for venous thrombosis, and also may be a beneficial therapeutic agent in arterial thrombosis.

Endogenous inhibitors of nitric oxide synthesis and lipid peroxidation in hyperlipidemic rabbits.

AIM: To examine whether the elevation of endogenous NG, NG-dimethylarginine (DMA) content is related to lipid peroxidation in the high lipid-fed rabbit. METHODS: In high lipid diet-fed rabbits, concentrations of serum cholesterol, triglyceride, malondialdehyde (MDA), and DMA were measured, and endothelium-dependent relaxation to acetylcholine (ACh) was tested. RESULTS: After 6-wk on a high lipid-diet, the levels of serum total cholesterol, triglyceride, MDA, and DMA were increased vs those in control group (MDA was 2.88 +/- s 0.20 vs 1.54 +/- 0.13 nmol.L-1, P < 0.01 and DMA was 1.51 +/- 0.07 vs 0.75 +/- 0.13 mumol.L-1, P < 0.01), while the endothelium-dependent vasodilation in the isolated thoracic aorta was impaired (the maximal response to ACh was 45.59 +/- 3.10 vs 76.93 +/- 5.68%). Supplementation with vitamin E decreased MDA and DMA content and improved the endothelium-dependent vasodilation. CONCLUSIONS: An increase in serum concentration of DMA may be secondary to the elevation of lipid peroxides in the hyperlipidemic rabbit.

[Studies on the analytical method of a new anti-arrhythmic guan-fu base A in rabbit plasma].

Guan-fu base A, a new antiarrhythmic alkaloid with a structure of C20-diterpenoid, was first isolated from the tuber of Aconitum coreanum (Levl.) Raipaics in China in 1966. An analytical method of GC-ECD has been established in this paper for the determination of its concentration in rabbit plasma in order to study its pharmacokinetics in preclinical pharmacology. Guan-fu base A and the internal standard alprenolol (ALP) was found to react rapidly and quantitatively with trifluoroacetic anhydride (TFAA) to produce derivatives GFA-TFAA and ALP-TFAA which were identified by GC-MSD. An optimal GC-ECD system for the separation and determination of the derivatives following the sample preparation was established. There was a wide linear range of the method from 10-2 x 10(4) ng/ml (r = 0.9984). The average recovery of Guan-fu base A from the spiked plasma was 97.52%. The coefficient of variation of between-day and within-day were less than 9% and 7%, respectively. The method was used to determine Guan-fu base A in the plasma of 15 rabbits following intravenous administration of 3 dosages of 0.4, 2 and 10 mg per kg of body weight.