Context Explore the clinical characteristics and influencing factors of immune thyroid dysfunction (ITD) caused by immune checkpoint inhibitors (ICIs) in the treatment of malignant tumors. Methods This was a retrospective study of cancer patients treated with ICIs between January 2019 and December 2021 at the Second Affiliated Hospital of Nanchang University. According to the occurrence of thyroid dysfunction, patients were divided into an ITD group and non-ITD group. We describe the clinical characteristics, autoantibody levels, and their impact on prognosis of patients with ICI-related ITD. Result A total of 560 cases meeting the criteria were included, with a median follow-up time of 11.0 months. The incidence of ITD was 50.7%. Baseline TSH levels (OR, 1.935/mcIU/L; 95% CI, 1.613-2.321; P < .001) and combination targeted therapy (OR, 2.101; 95% CI, 1.433-3.079; P < .001) were most strongly associated with the occurrence of ITD. The median time to ITD in patients receiving medication with ICIs was 73 (34.5-149) days. Of the 87 patients initially diagnosed with hyperthyroid ITD, 46 (52.9%) progressed to hypothyroidism over the course of the disease. Baseline anti-thyroglobulin antibody abnormalities were strongly associated with the occurrence of ITD (OR, 67.393; 95% CI, 5.637-805.656; P = .001). Overall survival was significantly lower in patients who did not develop ITD than in those who did (hazard ratio, 0.523; 95% CI, 0.599-0.97; P < .001). Conclusion The incidence of ICI-related ITD is high, and the course of the disease is rapidly changing, and thyroid function in patients treated with immunotherapy should be monitored to detect ITD and permit early intervention.

Background: Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Methods: Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. Results: The geometric mean serum TSH (2.5th–97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74–7.04 mIU/L) and 2.34 mIU/L (0.61–8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, p -value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27–4.2 mIU/L) and NACB standard interval in the TIDE study (0.74–7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%, p < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27–4.2 and 4.2–7.04 mIU/L TSH groups. Conclusions: Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.

Activation of hepatic stellate cells (HSCs) is a key inducer of liver fibrogenesis in nonalcoholic fatty liver disease (NAFLD). Exosomes play an important role between hepatocytes and HSCs. This study aims to explore the role of exosomes derived from palmitic acid (PA)-treated hepatocytes in regulating HSCs (LX-2 cell) proliferation and activation and the underlying mechanisms. Exosomes were isolated from PA-treated human normal hepatocytes and incubated with LX-2 cells. Cell Counting Kit-8 (CCK-8) was performed to determine LX-2 cell proliferation, and the expression of fibrosis markers α-smooth muscle actin (α-SMA) and collagen type 1 α1 (CoL1A1) were examined to evaluateLX-2 cell activation. PA induced hepatocytes to release more exosomes enriched in miR-107. Mechanically, on the one hand, exosomes from PA-treated hepatocytes shuttled miR-107 to LX-2 cells, where miR-107 activated Wnt signaling by targeting DKK1 and thereby induced LX-2 cell activation; on the other hand, PA-treated hepatocytes derived exosomes also delivered miR-107 to CD4 + T lymphocytes, where miR-107 elevated IL-9 expression by targeting Foxp1, which bound to the IL-9 promoter in CD4 + T cells and suppressed Th9 cell differentiation and reduced IL-9 expression, and thus promoted LX-2 cell activation by activating Raf/MEK/ERK signaling pathway.

Background: Iodine intake is associated with thyroid autoimmunity. In this study, we evaluated the changes in thyroid autoimmunity after 20 years of universal salt iodization (USI) in China. Methods: A total of 78,470 subjects (18 years or older) from 31 provincial regions of mainland China participated in the study. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), TSH receptor antibody, thyrotropin (TSH), and urinary iodine concentration (UIC) were measured. Results: Positive TPOAb and TgAb were detected in 10.19% [CI 9.80–10.59] and 9.70% [CI 9.28–10.13] of the subjects, respectively. The prevalence of positive isolated TPOAb (i-TPOAb), positive isolated TgAb (i-TgAb), and double positive TPOAb and TgAb (d-Ab) was 4.52%, 4.16%, and 5.94%, respectively. The prevalence of thyroid antibody positivity was the highest in the iodine-deficient (UIC <100 μg/L) groups. The prevalence of i-TPOAb was inversely associated with more than adequate iodine intake (MAI) and excessive iodine intake (EI); the odds ratio (OR) was 0.89 [CI 0.81–0.98] for MAI and 0.90 [CI 0.81–0.99] for EI. We observed that i-TgAb, like i-TPOAb, was a high-risk factor for subnormal TSH levels (OR = 3.64 [CI 2.62–5.05]) and elevated TSH levels (OR = 1.62 [CI 1.49–1.77]). The prevalence of thyroid antibody positivity varied among five ethnic groups. Conclusions: After two decades of USI, the prevalence of thyroid antibody positivity has remained low. MAI and EI had an inverse relationship with TPOAb positivity, which reveals that UIC between 100 and 299 μg/L is optimal and safe for thyroid autoimmunity. These conclusions need to be confirmed in a follow-up study because this study was a cross-sectional study.

Background: The triglyceride glucose (TyG) index has been proved to be a reliable marker of diabetic kidney disease (DKD).Objective: We further investigated the association between TyG index, and its derivative, triglyceride-glucose body mass index (TyG-BMI), and the risk of DKD among adults with newly diagnosed type 2 diabetes (T2D).Methods: This cross-sectional study was conducted among patients with newly diagnosed T2D. We assessed the correlation between TyG index, TyG-BMI, and the risk of DKD using logistic regression analysis, restricted cubic spline analysis, trend tests, receiver operating characteristic curve, and subgroup analyses.Results: Among the 924 included patients, 199 (21.5%) had DKD. Logistic regression revealed that TyG index (odds ratio [OR] 1.232, 95% confidence interval [CI] 1.064–1.428, p = 0.005) and TyG-BMI (OR 1.003, 95% CI 1.000–1.006, p = 0.021) were risk factors for DKD. The trend test demonstrated a dose–response association between TyG index (p for trend = 0.004), TyG-BMI (p for trend = 0.035), and the risk of DKD. Restricted cubic spline analysis indicated a nonlinear correlation between TyG index and the risk of DKD, with an increase in the risk of DKD when the TyG index was greater than 9.68 (p for nonlinearity = 0.014). In contrast, TyG-BMI and the risk of DKD exhibited a linear dose–response relationship, with an increase in the risk of DKD when the TyG-BMI was greater than 243 (p for nonlinearity = 0.034). According to the receiver operating characteristic curve, the optimal cutoff values for TyG index and TyG-BMI were 10.08 and 221.5, respectively.Conclusion: Among newly diagnosed T2D patients, the risk of DKD increases with the increase of TyG index and TyG-BMI, with their respective cut-off values being 9.68 and 243. Both TyG index and TyG-BMI have poor diagnostic value for the risk of DKD.

Objective: We investigated the relationship between thyroid hormones and the risk of diabetic kidney disease (DKD) progression. Methods: A total of 452 patients with type 2 diabetes were included, and a cross-sectional analysis was performed. Urine albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to diagnose persistent albuminuria and stage chronic kidney disease, respectively. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline was used to describe the risk of DKD progression (low, moderate, and high or very high risks). Results: The DKD group had higher levels of thyroid-stimulating hormone (TSH) and lower levels of free triiodothyronine (FT₃) and free thyroxine (FT₄) than the non-DKD group. The prevalence of thyroid dysfunction in the DKD group was significantly higher than in the non-DKD group, especially the prevalence of subclinical hypothyroidism. FT₃ levels decreased gradually with the deterioration of DKD. TSH levels increased with an increasing KDIGO category. FT₃ and FT₄ levels were negatively correlated with serum creatinine levels and ACR, and positively correlated with eGFR. Contrastingly, TSH was positively correlated with ACR, and negatively correlated with eGFR. After adjustment, an increase in FT₃ levels significantly reduced the risk of DKD [odds ratio, OR (95% confidence interval, CI)=0.58 (0.42– 0.79)] and DKD progression [ORs (95% CIs)=0.65 (0.45– 0.93) for the moderate risk group and 0.50 (0.33– 0.74) for the high or very high-risk group, using the low-risk group as a reference]. FT₃ levels below 4.30 pmol/L in men and 3.99 pmol/L in women were the cut-off points for an increased risk of DKD progression. Conclusion: Low FT₃ level is an independent risk factor for DKD and DKD progression. FT₃ ≤ 4.30 pmol/L in men and ≤ 3.99 pmol/L in women will greatly increase the risk of kidney disease progression in patients with type 2 diabetes.