Clearly fluorescent delineating ER+ breast tumor incisal edge and identifying tiny metastatic tumor foci at high resolution.

Fluorescence-image guided surgery (FGS) can intraoperatively provide real-time visualization of a tumor incisal edge and high-resolution identification of tumor foci to improve treatment outcomes. In this contribution, we report a fluorescent probe NB-TAM based on intramolecularly folded photoinduced electron transfer (PET), which displayed a prominent turn-on response in the near-infrared (NIR) window upon specific interaction with the estrogen receptor (ER). Significantly, NB-TAM could delineate a clear tumor incisal edge (tumor-to-normal tissue ratio > 5) in a 70-min time window, and was successfully used to guide the facile and precise resection of ER+ breast tumors in mice. To our surprise, NB-TAM was found to be capable of identifying very tiny lung metastatic ER+ breast tumor foci (0.4 × 0.3 mm), and this ultrahigh resolution was essential to effectively promote tumor resection precision and early diagnosis of tiny tumors. These results clearly elucidate the promising application of NB-TAM as a diagnostic agent for intraoperative fluorescence imaging of ER+ breast cancer.

Clinical risk factors and cancer risk of thyroid imaging reporting and data system category 4 A thyroid nodules.

PURPOSE: Beyond the Thyroid Imaging Reporting and Data System (TIRADS) classification of thyroid nodules, additional factors must be weighed in the decision to perform fine needle aspiration (FNA). In this study, we aimed to identify risk factors for malignancy in patients with ultrasound-classified Chinese-TIRADS (C-TIRADS) 4 A nodules. METHODS: Patients who underwent thyroid FNA at our institution between May 2021 and September 2022 were enrolled. We collected demographic data, including age, sex, previous radiation exposure, and family history. An in-person questionnaire was used to collect lifestyle data, such as smoking habits and alcohol consumption. Body mass index (BMI) was calculated. The serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured. Prior to FNA, ultrasonic inspection reports were reviewed. The cytologic diagnoses for FNA of thyroid nodules followed the Bethesda System for Reporting Thyroid Cytopathology (2017). RESULTS: Among the 252 C-TIRADS 4 A nodules, 103 were malignant. Compared to those in the benign group, the patients in the malignant group had a younger age (42.2 ± 13.6 vs. 51.5 ± 14.0 years, P < 0.001). Logistic regression showed that advanced age was associated with a lower risk of malignancy in C-TIRADS 4 A nodules (OR = 0.95, 95% CI 0.93 ~ 0.97, P < 0.001). We demonstrated a decreased risk of malignancy in patients with 48.5 years or older. CONCLUSION: Advanced age was associated with a decreased risk of malignancy in patients with C-TIRADS 4 A nodules. This study indicated that in addition to sonographic characteristics, patient age should be considered when assessing the risk of malignancy.

Lipid Droplet Targeting Type I Photosensitizer for Ferroptosis via Lipid Peroxidation Accumulation.

As an iron-dependent lipid peroxidation (LPO) mediated cell death pathway, ferroptosis offers promises for anti-tumor treatment. Photodynamic therapy (PDT) is an ideal way to generate reactive oxygen species (ROS) for LPO. However, the conventional PDT normally functions on subcellular organelles, such as endoplasmic reticulum, mitochondria, and lysosome, causing rapid cell death before triggering ferroptosis. Herein, the first lipid droplet (Ld)-targeting type I photosensitizer (PS) with enhanced superoxide anion (O2 -· ) production, termed MNBS, is reported. The newly designed PS selectively localizes at Ld in cells, and causes cellular LPO accumulation by generating sufficient O2 -· upon irradiation, and subsequently induces ferroptosis mediated chronical PDT, achieving high-efficient anti-tumor PDT in hypoxia and normoxia. Theoretical calculations and comprehensive characterizations indicate that the Ld targeting property and enhanced O2 -· generation of MNBS originate from the elevated H-aggregation tendency owing to dispersed molecular electrostatic distribution. Further in vivo studies using MNBS-encapsulated liposomes demonstrate the excellent anti-cancer efficacy as well as anti-metastatic activity. This study offers a paradigm of H-aggregation reinforced type I PS to achieve ferroptosis-mediated PDT.

High prevalence of metabolic diseases, liver steatosis and fibrosis among Chinese psychiatric patients.

BACKGROUND: We aimed to investigate the differences of metabolic disorders between the general population and psychiatric patients, with an emphasis on the prevalence and influencing factors of liver fibrosis in psychiatric patients. METHODS: A total of 734 psychiatric patients and 734 general population matched for age, sex, and BMI were enrolled from Shanghai, China. All participants underwent blood pressure, glucose, lipid profile measurements, and anthropometric parameters including body weight, height and waist circumference. FibroScan examinations were also performed on psychiatric patients. Liver steatosis and fibrosis were diagnosed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by professional staff. RESULTS: Compared with the general population, psychiatric patients revealed significantly higher burden of metabolic disorders. The overall prevalence of liver steatosis (CAP ≥ 233 dB/m) and fibrosis (LSM ≥ 7.0 kPa) was 48.7% and 15.5% in psychiatric patients. Psychiatric patients with liver steatosis or fibrosis showed worse metabolic profile. Meanwhile, the prevalence of liver fibrosis was also significantly higher in patients with overweight, central obesity, diabetes, hypertension, metabolic syndrome, and liver steatosis. In logistic regression analyses, age, BMI and visceral adiposity index were independent risk factors for liver fibrosis in psychiatric patients. Additionally, antipsychotic medication was suggested to be associated with an increased risk of liver fibrosis in psychiatric patients with liver steatosis. CONCLUSIONS: Prevalence of liver steatosis and fibrosis is high in Chinese psychiatric patients. Those with antipsychotic polypharmacy and obesity are at high risk, and may benefit from early liver assessment in preventing fibrosis progression.

Recombinant human p53 adenovirus injection combined with Bortezomib inhibits proliferation and promotes apoptosis in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a B-cell malignancy characterized by abnormal proliferation of clonal plasma cells in the bone marrow, the incidence of which has further increased in recent years. In multiple myeloma, wild-type functional p53 is often inactivated or dysregulated. Therefore, this study aimed to investigate the role of p53 knockdown or overexpression in multiple myeloma and the therapeutic effect of recombinant adenovirus-p53 (rAd-p53) in combination with Bortezomib. METHODS: SiRNA p53 and rAd-p53 were used to knock down and overexpress p53. RT-qPCR was used to detect gene expression, and western blotting (WB) was used to detect protein expression levels. We also constructed wild-type multiple myeloma cell line-MM1S cell xenograft tumor models and explored the effects of siRNA-p53, rAd-p53, and Bortezomib on multiple myeloma in vivo and in vitro. H&E staining and KI67 immunohistochemical staining were used to assess the anti-myeloma effects of recombinant adenovirus and Bortezomib in vivo. RESULTS: The designed siRNA p53 effectively led to the knockdown of the p53 gene, while rAd-p53 could significantly achieve p53 overexpression. p53 gene inhibited MM1S cell proliferation and promoted apoptosis of wild-type multiple myeloma cell line MM1S. P53 gene inhibited tumor proliferation in vitro by promoting p21 expression and reducing cell cycle protein B1 expression of MM1S. P53 gene overexpression could inhibit tumor growth in vivo. Injection of rAd-p53 in tumor models inhibited tumor development through p21- and cyclin B1-mediated cell proliferation and apoptosis regulation. CONCLUSIONS: We found that overexpression of p53 inhibits MM tumor cell survival and proliferation in vivo and in vitro. Furthermore, the combination of rAd-p53 and Bortezomib significantly improved the efficacy, which provides a new possibility for more effective treatment of MM.

Carrier-Free ATP-Activated Nanoparticles for Combined Photodynamic Therapy and Chemotherapy under Near-Infrared Light.

The combination of photodynamic therapy (PDT) and chemotherapy (chemo-photodynamic therapy) for enhancing cancer therapeutic efficiency has attracted tremendous attention in the recent years. However, limitations, such as low local concentration, non-suitable treatment light source, and uncontrollable release of therapeutic agents, result in reduced combined treatment efficacy. This study considered adenosine triphosphate (ATP), which is highly upregulated in tumor cells, as a biomarker and developed ingenious ATP-activated nanoparticles (CDNPs) that are directly self-assembled from near-infrared photosensitizer (Cy-I) and amphiphilic Cd(II) complex (DPA-Cd). After selective entry into tumor cells, the positively charged CDNPs would escape from lysosomes and be disintegrated by the high ATP concentration in the cytoplasm. The released Cy-I is capable of producing single oxygen (1 O2 ) for PDT with 808 nm irradiation and DPA-Cd can concurrently function for chemotherapy. Irradiation with 808 nm light can lead to tumor ablation in tumor-bearing mice after intravenous injection of CDNPs. This carrier-free nanoparticle offers a new platform for chemo-photodynamic therapy.

Tumor Cell-Responsive Photodynamic Immunoagent for Immunogenicity-Enhanced Orthotopic and Remote Tumor Therapy.

Combining photodynamic therapy (PDT) and immune checkpoint blockades is an efficient method to maximize immunotherapeutic outcome by boosting tumor immunogenicity and modulating the immunosuppressive tumor microenvironment. However, the always-on bioactivity of photosensitizers or immune checkpoint inhibitors leads to uncontrollable side effects, limiting the in vivo therapeutic efficacy of treatments. An activatable strategy is of great importance for improving the selectivity during cancer therapy. In this study, a photodynamic immunomodulator, ICy-NLG, is developed by conjugating the photosensitizer ICy-NH2 with the indoleamine 2,3-dioxygenase 1 inhibitor NLG919 through a glutathione (GSH)-cleavable linker to achieve activatable photodynamic immunotherapy. The conjugation considerably suppresses both the PDT effect and the activity of the inhibitor. After ICy-NLG is activated by high levels of GSH in tumor cells, the PDT effect is restored and leads to immunogenic tumor cell death. The released tumor-associated antigens in conjunction with the activated immune checkpoint inhibitor induce a synergistic antitumor immune response, resulting in the growth inhibition of primary and distant tumors and the prevention of lung metastasis in mouse xenograft models.

Detection of BRAF V600E in Fine-Needle Aspiration Samples of Thyroid Nodules by Droplet Digital PCR.

Background: BRAF exon 15 p.V600E (BRAF V600E) mutation has been established as an important molecular marker for papillary thyroid carcinoma diagnosis by ultrasound-guided fine-needle aspiration biopsy (FNAB). Sanger sequencing is the gold standard for detecting BRAF V600E mutations but fails to identify low-frequency mutations. However, droplet digital PCR (ddPCR) is a popular new method for detecting low-frequency mutations. Here, we compare the efficiency of droplet digital PCR (ddPCR) and Sanger sequencing for detection of the BRAF V600E mutation in thyroid fine-needle aspiration (FNA) samples. Methods: Thyroid fine-needle aspiration samples from 278 patients with 310 thyroid nodules were collected. Sanger sequencing and ddPCR were conducted to detect the BRAF V600E mutation. Results: The BRAF V600E mutation was found in 94 nodules (30.32%) by ddPCR and 40 nodules (12.90%) by Sanger sequencing in 310 FNA samples. A total of 119 nodules were confirmed PTC by postsurgical pathology. Among which the BRAF mutation was found in 80 (67.23%) nodules by ddPCR and 31 (26.05%) by Sanger sequencing. All nodules carrying the mutation detected by Sanger sequencing (SS+) were verified by ddPCR (ddPCR+). Also, all nodules with no mutation detected by ddPCR were interpreted as wild-type by Sanger sequencing (SS-). In addition. Almost all SS+/ddPCR + nodules (95.00%; 38/40) and SS-/ddPCR + nodules (100.00%; 54/54) displayed a BRAF mutation rate of >5% and <15%, respectively, indicating easy misdetection by Sanger sequencing when the mutation rate is between 5 and 15%. Conclusion: ddPCR has higher sensitivity than Sanger sequencing and we propose ddPCR as a supplement to Sanger sequencing in molecular testing of BRAF using FNAB samples.

A five-gene panel refines differential diagnosis of thyroid nodules.

BACKGROUND: Molecular testing for oncogenic mutations in fine-needle aspiration has showed high predictive value in identifying malignant lesions from thyroid nodules with indeterminate cytology. METHODS: To figure out an efficient and economical gene panel for most medical institutions in China, we designed a five-gene panel including BRAF/NRAS/KRAS/HRAS/TERT genes and conducted a retrospective study to evaluate the role of this five-gene diagnostic panel in differential diagnosis of thyroid nodules. RESULTS: A total of 665 patients with 695 thyroid nodules were investigated in the current study. The fine-needle aspiration biopsy and surgically separated thyroid tissue specimens were harvested to test BRAF, TERT, NRAS, KRAS, and HRAS mutations. We identified 261 mutations in 665 patients, including 177 V600E mutations in BRAF. Three hundred and sixty-nine patients who underwent thyroid surgery after completion of the initial clinical and cytological evaluation were enrolled in the final analysis. The diagnostic sensitivity, specificity, and accuracy of the combination of FNAB cytology and five-gene detection were 74.7%, 93.8%, and 84.8%, respectively. BRAF V600E and five-gene panel could recognize 46.4% and 53.6% of papillary thyroid carcinoma in the patients with cytologically indeterminate nodules. CONCLUSION: The five-gene panel can effectively improve the sensitivity, negative predictive value, and accuracy of fine-needle aspiration biopsy cytology, especially in the patients with cytologically indeterminate nodules.

Blood lead, vitamin D status, and albuminuria in patients with type 2 diabetes.

Environmental lead exposure has been linked with reduced kidney function. However, evidence about its role in diabetic kidney damage, especially when considering the nutritional status of vitamin D, is sparse. In this observational study, we investigated the association between low-level lead exposure and urinary albumin-to-creatinine ratio (UACR) and assessed potential impact of vitamin D among 4033 diabetic patients in Shanghai, China. Whole blood lead was measured by graphite furnace atomic absorption spectrometry. Serum 25-hydroxyvitamin D [25(OH)D] was tested using a chemiluminescence immunoassay. The associations of blood lead with UACR and albuminuria, defined as UACR ≥30 mg/g, according to 25(OH)D levels were analyzed using linear and Poisson regression models. A doubling of blood lead level was associated with a 10.7% higher UACR (95% CI, 6.19%-15.5%) in diabetic patients with 25(OH)D < 50 nmol/L, whereas the association was attenuated toward null (2.03%; 95% CI, -5.18% to 9.78%) in those with 25(OH)D ≥ 50 nmol/L. Similarly, the risk ratios of prevalent albuminuria per doubling of blood lead level between the two groups were 1.09 (95% CI, 1.03-1.15) and 0.99 (95% CI, 0.86-1.14), respectively. Joint analysis demonstrated that a combination of high blood lead and low 25(OH)D corresponded to significantly higher UACR. Among diabetic patients with 25(OH)D < 50 nmol/L, the increment of UACR relative to blood lead was more remarkable in those with reduced estimated glomerular filtration rate (<60 mL/min/1.73 m2). These results suggested that higher blood lead levels were associated with increased urinary albumin excretion in diabetic patients with vitamin D deficiency. Further prospective studies are needed to validate our findings and to determine whether vitamin D supplementation yields a benefit.

Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study.

BACKGROUND: Uric acid (UA) is the end product of purine metabolism, which is thought to be related to many human diseases, such as nephrolithiasis, gout, cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome. However, the relationship between serum UA (SUA) and 25(OH) D is still unclear in the eastern Chinese population. METHODS: We did a population-based observational investigation, which included 12,770 residents living in eastern China. Ultimately, data from 9220 subjects were analyzed. Serum 25(OH) D, SUA, fasting plasma glucose (FPG), fasting insulin, HbA1c and other metabolic parameters were tested. Waist circumference (WC), weight and height were also measured. Questionnaires were collected from these subjects for information on smoking and drinking status. RESULTS: We enrolled 9220 Chinese adults, including 3681 males (age 55.57 ± 13.23 years) and 5539 females (age 54.31 ± 12.83 years). The levels of SUA were 352.07 ± 79.25 nmol/L and 269.29 ± 64.68 nmol/L in males and females, respectively. The proportion of adults with hyperuricemia (HUA) was 12.26% in the total population. Levels of SUA were positively associated with 25(OH) D, and the incidence of HUA increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001). CONCLUSIONS: SUA was positively associated with 25(OH) D in the eastern Chinese population. Higher levels of serum 25(OH) D may be a potential predictor of HUA.

Prevalence of hyperuricaemia in an Eastern Chinese population: a cross-sectional study.

OBJECTIVES: In the past decade, China has been characterised by large-scale urbanisation as well as rapid economic growth. The aim of this study was to further investigate the prevalence of hyperuricaemia (HUA) in an Eastern Chinese population. DESIGN: Cross-sectional study. SETTING: Survey of Prevalence in East China of Metabolic Diseases and Risk Factors China study. PARTICIPANTS: In this study, 12 770 residents from 22 sites in Eastern China were recruited. Finally, 9225 subjects were included. MAIN OUTCOME MEASURES: The serum levels of uric acid (UA), fasting plasma glucose (FPG), glycated haemoglobin and other metabolic parameters were tested. Waist circumference, weight, height and blood pressure were also measured. Questionnaires regarding smoking, drinking, education were collected from the subjects. HUA was defined as serum UA >420 µmol/L for men and >360 µmol/L for women. RESULTS: The prevalence of HUA in this Eastern Chinese population was 11.3% (9.9, 12.7) overall, 20.7% (17.7, 23.7) in men and 5.6% (4.3, 6.7) in women. The prevalence of HUA in urban subjects was higher than that in rural subjects (12.9 vs 10.8%, p<0.01). The prevalence of HUA was negatively and positively associated with age in men and women, respectively. Residents with high body mass index levels had a higher prevalence of HUA. In the logistic regression analysis, male sex, urban residency, total cholesterol, triglyceride, overweight, obesity, systolic blood pressure and low economic status were independently correlated with HUA. CONCLUSIONS: The estimated prevalence of HUA in this Eastern Chinese population was 11.3% (9.9, 12.7) overall and 20.7% (17.7, 23.7) and 5.6% (4.3, 6.7) in men and women, respectively. HUA has gradually become an important public health issue in China. TRIAL REGISTRATION NUMBER: ChiCTR-ECS-14005052.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects.

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-ß had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-ß going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-ß no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

A singlet oxygen self-reporting photosensitizer for cancer phototherapy.

Photodynamic cancer therapy has attracted great attention with the increasing threat of tumors, and improving its therapeutic efficacy is highly desirable. However, due to the highly efficient intersystem crossing potency to generate singlet oxygen (1O2), high-efficiency photosensitizers often suffer from weak fluorescence and excess injury to normal tissue. To overcome these obstacles, here we show a reliable self-reporting strategy for real-time monitoring of therapeutic progression. As a proof of concept, a molecular dyad is designed by connecting benzo[a]phenoselenazinium (NBSe) to rhodamine (Rh), namely Rh-NBSe, where the fluorescence of the Rh unit is initially suppressed by the fluorescence resonance energy transfer mechanism, but enabled to recover as feedback signal once the reaction with photosensitized 1O2 takes place. The observed fluorescence increases by irradiation in vitro and in vivo successfully reflect the real-time 1O2 generation speed in photodynamic therapy. In addition, the favorable therapeutic advantages of Rh-NBSe are also verified, for example, the high Φ Δ (0.8) and the low IC50 (0.2 µM, 6 J cm-2). Based on the therapeutic ability and real-time 1O2 self-reporting ability, Rh-NBSe demonstrates significant potential for self-regulating phototherapy.

The Association of Thyroid Nodules with Metabolic Status: A Cross-Sectional SPECT-China Study.

PURPOSE: The aim of this study was to investigate the association of thyroid nodules (TNs) and their ultrasound (US) characteristics related to malignancy with metabolic status. METHODS: The data were obtained from a cross-sectional study (SPECT-China, 2014-2015). The study included 9898 participants older than 18 years. Participants underwent several checkups, which included the measurement of anthropometric parameters, blood pressure, TSH levels, glucose, and lipid profiles. TN and nonalcoholic fatty liver disease (NAFLD) were diagnosed by US. TN US characteristics, including microcalcification and a taller-than-wide shape, were recorded. RESULTS: Participants with TN [TN(+)] had a higher prevalence of metabolic syndrome (Met-S), obesity, central obesity, hyperlipidaemia, diabetes, hypertension, and NAFLD, especially women (all P ≤ 0.001). After full adjustment, logistic regression analysis indicated that metabolic syndrome, obesity, central obesity, and hyperlipidaemia were all independent risk factors for the increased prevalence of TN in both genders (P < 0.05). In terms of TN US imaging characteristics associated with malignancy, being female with obesity, central obesity, and NAFLD had 1.91-fold, 2.09-fold, and 1.75-fold increased risks of developing a taller-than-wide nodule (P = 0.014, 0.004, and 0.027, resp.). CONCLUSIONS: The status of metabolic disorders might be associated with higher risks of TN in both genders. In women, obesity, central obesity, and NAFLD might contribute to the development of a taller-than-wide nodule. The potential role of metabolic status in the pathogenesis of the thyroid nodule and thyroid cancer remains to be elucidated.

Sexual Dimorphism for the Association between Vitamin D and Insulin Resistance in Chinese People.

BACKGROUND: The relationship between vitamin D and insulin resistance is still controversial. Many factors could influence this relationship. In addition, this relationship in different genders was still unclear. METHODS: A total of 6597 subjects, including 2813 males and 3784 females, were analyzed. The serum levels of 25(OH)D, fasting blood glucose (FBG), fasting insulin, HbA1c, and other metabolic parameters were tested. The waist circumference (WC), weight, and height were also measured. Questionnaires regarding smoking and drinking were collected from these subjects. RESULTS: Serum 25(OH)D was categorized into quartiles. Increasing 25(OH)D levels were associated with reduced trend of homeostasis model assessment of insulin resistance (HOMA-IR) in both males and females. Pearson's correlation indicated 25(OH)D level was inversely associated with the HOMA-IR for male subjects (r = -0.055, P = 0.028) but not for female subjects (r = -0.005, P = 0.798). Age, triglyceride (TG), and low-density lipoprotein (LDL) were associated with the vitamin D levels in males and females. In regression analysis, serum 25(OH)D concentration was significantly associated with HOMA-IR only in overweight males. CONCLUSION: We found an inverse association between 25(OH)D and HOMA-IR in Chinese overweight males. Vitamin D supplementation might be beneficial in this population. However, further clinical trials are needed to confirm this association.

Are thyroid nodules associated with sex-related hormones? A cross-sectional SPECT-China study.

OBJECTIVE: Little is known about the association between thyroid nodules (TNs) and endogenous sex hormones. We aimed to investigate the relationship between TNs and sex-related hormones among men in China. SETTING: The data were obtained from a cross-sectional study Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China study, 2014-2015) based on the population. PARTICIPANTS: In total, 4024 men over 18 years of age who were not using hormone replacement therapy and who underwent complete assays of the serum total testosterone (T), oestradiol (E2), follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone-binding globulin (SHBG) levels as well as thyroid ultrasonography (US) enrolled in this study. RESULTS: Of the 4024 participants (54.15±13.08 years old), 1667 participants (41.4%) had TNs. Men with TN(s) (TN(+) group) had significantly lower levels of total T and SHBG and higher E2/T levels compared with the men without TN(s) (TN(-) group) (p<0.05). The TN prevalence decreased with the quartiles of the SHBG level (p<0.05). Binary logistic analysis showed that lower quartiles of SHBG had a greater risk of TN(s) (all p for trend <0.05). This association persisted in the fully adjusted model (p for trend=0.017), in which, for the lowest compared with the highest quartile of SHBG, the OR of TN(s) was 1.42 (95% CI 1.07 to 1.89). No statistically significant association was found between sex-related hormones and US characteristics associated with malignancy (nodule >10 mm, microcalcification and a 'taller' than 'wider' shape). CONCLUSIONS: TNs are highly prevalent in men in China. A lower SHBG level was significantly associated with TN among men. The potential role of SHBG in the pathogenesis of the TN remains to be elucidated.

Lead and cadmium exposure, higher thyroid antibodies and thyroid dysfunction in Chinese women.

BACKGROUND: Exposure to lead(Pb) or cadmium(Cd) has been related to decreasing thyroxine in many previous studies. The underlying mechanisms have not been clarified. Heavy metal-induced thyroid autoimmunity in pregnant women has been found, despite having been rarely explored in the general population. OBJECTIVES: We aimed to determine whether the blood levels of lead(BPb) or cadmium(BCd) related to the levels of sera antibodies to thyroid proteins and thyroid dysfunction in the general population. METHODS: Our study included 5628 Chinese adults and was based on the 2014 SPECT-China study. Thyroid dysfunction and subclinical thyroid dysfunction were defined by total triiodothyronine (TT3), total thyroxine(TT4) and thyroid stimulating hormone (TSH).Thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies (TGAb), TT3, TT4, and TSH were measured by immunochemiluminometric assays. BPb and BCd levels were tested by atomic absorption spectrometry. Linear and logistic regression models were used to analyze the associations. RESULTS: After adjustment for age, body mass index, smoking status (men only) and drinking status, the natural log(ln) BPb was positively related to the lnTPOAb (B = 0.062, P < 0.05) and to the lnTSH (B = 0.047, P < 0.01) in women. The lnBCd in women was positively related to the lnTGAb (B = 0.046, P < 0.05). In the adjusted logistic regression models, the BCd of women was positively related to their hypothyroid status and TGAb tertiles. The ORs of women in the middle and higher TPOAb tertiles were 1.38 (P < 0.001) and 1.35 (P < 0.001) times greater for every ln-unit increase in BPb, respectively. In men, no continuous correlation was found among variables. CONCLUSIONS: In women, BPb and BCd levels were related to higher TSH and hypothyroid status, respectively, suggesting a Pb and Cd induction of sex-biased thyroid autoimmunity.

A Higher Ratio of Estradiol to Testosterone Is Associated with Autoimmune Thyroid Disease in Males.

BACKGROUND: Autoimmune thyroid disease (AITD) is highly prevalent. Although AITD is less common in males, it is unclear whether estradiol (E2) combined with total testosterone (T) contributes to the prevalence of AITD. This study evaluated the association between the E2/T ratio and the prevalence of AITD in males. METHODS: The data were obtained from a cross-sectional population-based study, the SPECT-China study, 2014-2015. A total of 4109 males ≥18 years of age were enrolled in this study. Participants underwent several checkups, which included assays of serum E2, T, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels, as well as thyroid ultrasonography (US). AITD was defined based on the presence of TPOAb and TgAb levels, and the presence of thyroid US findings. RESULTS: Overall, the prevalence of positivity for TPOAb and/or TgAb (TPO/TgAb[+]) was 11.02%, and the positivity for TPOAb and/or TgAb together with US (TPO/TgAb[+] and US[+]) was 4.58%. The E2/T ratio levels were significantly higher in the TPO/TgAb(+) group and the TPO/TgAb(+) and US(+) group (7.91 ± 8.03 vs. 7.19 ± 10.30, p = 0.003; 8.78 ± 11.26 vs. 7.19 ± 10.30, p = 0.001) compared to the TPO and TgAb(-) group. The prevalence of TPO/TgAb(+) and US(+) significantly increased with an increasing E2/T ratio (p = 0.013). Binary logistic analysis showed that increased E2/T ratio levels were associated with an increased risk of AITD (TPO/TgAb[+]: odds ratio = 1.35, p = 0.002; TPO/TgAb[+] and US[+]: odds ratio = 1.48, p = 0.006). CONCLUSIONS: AITD is highly prevalent in males in China. Higher E2/T ratios were significantly associated with AITD among males. Further studies will be needed to assess whether there is a causal relationship between E2/T ratios and AITD.

Cadmium exposure and its association with serum uric acid and hyperuricemia.

Few studies have investigated the association between serum uric acid (UA) and cadmium exposure. Our previous study revealed a significantly higher blood cadmium (CdB) level in the Chinese population compared to populations in other countries. To determine whether CdB in Chinese adults is associated with serum UA and hyperuricemia, 2996 participants from the cross-sectional SPECT-China study were recruited. CdB was measured by atomic absorption spectrometry. Hyperuricemia was defined as a serum UA concentration ≥416.4 µmol/L for men and ≥356.9 µmol/L for women. Regression analyses were used to analyze the association of CdB with serum UA and hyperuricemia. We found that the median CdB level was higher in men with hyperuricemia (2.40 µg/L) than in men without hyperuricemia (1.98 µg/L, P < 0.05). A positive relationship between serum UA and CdB was found in Chinese men after adjusting for the estimated glomerular filtration rate (eGFR), current smoking status, diabetes, dyslipidemia, hypertension and body mass index and in participants with eGFR > 60 mL/min per 1.73 m2. Further, the odds ratio of hyperuricemia increased with increasing CdB quartiles (P for trend < 0.05) in men. In conclusion, CdB was positively related to the serum UA level and to hyperuricemia in Chinese men but not in Chinese women.