[The 509th case: fatigue, sleepiness, mood disorder, and hypothyroidism].

A 28-year-old woman presented with a 4-year history of fatigue and sleepiness and was found to have central hypothyroidism and mood disorder. The patient had normal thyroid volume and did not show any other pituitary axis involvement. Over the course of the disease, her symptom improvement matched with the free thyroxine (FT4) rebound and the adjustment of antipsychotic medication. The patient's grandmother had central hypothyroidism, and her mother and uncle had lowered or inappropriately normal thyroid stimulating hormone. Hence, genetic involvement was highly suspected, but whole exon sequencing did not reveal a pathogenic variant. Levothyroxine tablets were prescribed to maintain a normal median level of FT4, and mood disorder medications were adjusted by specialists. Isolated central hypothyroidism is extremely rare, and we report this case aiming to raise awareness of this condition.

[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.

Linoleic acid and α-linolenic acid inhibit conjugative transfer of an IncX4 plasmid carrying mcr-1.

AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

Novel SLCO2A1compound heterozygous mutation causing primary hypertrophic osteoarthropathy with Bartter-like hypokalemia in a Chinese family.

PURPOSE: Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis and pachydermia with defects in the degradation of prostaglandin E2 (PGE2). Mutations in SLCO2A1 gene-encoding prostaglandin transporter (PGT) resulted in PHO, autosomal recessive 2 (PHOAR2). The spectrum of mutations and variable clinical complications of PHOAR2 has been delineated. In this study, we investigated a Chinese PHO family with a manifestation of Bartter-like hypokalemia. METHODS: Clinical manifestations were collected and genetic analyses were performed in the PHO family. RESULTS: The 33-year-old male proband had severe hypokalemia due to potassium loss from the kidney, while his brother had mild hypokalemia. After being treated with etoricoxib, the serum potassium level of the patient increased rapidly to the normal range which corresponded with the reduction in his serum PGE2 and PE2 metabolite (PGEM) levels. A novel SLCO2A1 compound heterozygous mutation of p.I284V and p.C459R was identified in two PHO patients in this family. CONCLUSIONS: The present findings supported that the Bartter-like hypokalemia is a new complication of PHOAR2 caused by the high level of PGE2. Etoricoxib was demonstrated to be effective for the renal hypokalemia in PHO patients.

Exploration on the relationship between the elderly osteoporosis and cardiovascular disease risk factors.

OBJECTIVE: To explore and discuss the correlation between osteoporosis and the risk factors of cardiovascular diseases in the elderly. PATIENTS AND METHODS: A total of 1240 patients, who were hospitalized in our hospital from January 2012 to January 2017, with the age ≥ 65 years old, were selected. All the patients were divided into osteoporosis group and normal bone mass group according to their bone mineral density. The general conditions, biochemical indexes, combined cardiovascular diseases, and the related risk factors, were recorded and analyzed. RESULTS: The proportion of patients with coronary heart diseases, hyperlipidemia, diabetes mellitus, and smoking in osteoporosis group was significantly higher than that in normal bone mass group (p < 0.05). Results of binary logistic regression analysis showed that homocysteine (HCY), low density lipoprotein (LDL) and total cholesterol (TC) were the major risk factors of osteoporosis in the elderly patients. High-density lipoprotein (HDL) and body weight were protective factors for senile patients with osteoporosis. Female, hypertension, coronary heart diseases, hyperlipidemia, and diabetes mellitus were the main risk factors of complication in the elderly patients with osteoporosis. CONCLUSIONS: Senile osteoporosis is closely correlated with cardiovascular diseases and related risk factors, including hypertension, coronary heart disease as well as hyperlipidemia, and should be early prevented and treated.