Serum klotho associated with thyroid hormone in adults: A population-based cross-sectional research.

BACKGROUND AND STUDY AIM: The klotho protein, a multifunctional protein, has been shown to be associated with a wide range of endocrine diseases and has been linked to thyroid tumourigenesis. However, the relationship between serum klotho levels and thyroid hormones remains poorly understood. This study aimed to explore the correlation between serum klotho levels and thyroid hormones. METHODS: Data was obtained from the NHANES cycles 2007-2008, 2009-2010, and 2011-2012. A total of 4674 participants were recruited for this study. Statistical analysis was using multiple linear regression analyses, and restricted cubic spline plots (RCS) to investigate the association between serum klotho levels and serum levels of thyroid hormones. RESULTS: In the unadjusted covariate model, ln(klotho) significantly positively correlated with tT3, tT4, fT3, tT4/fT4, and tT3/fT3 (all P<0.01) and negatively correlated with TSH, tT4/tT3, and fT4/fT3 (all P<0.05). Furthermore, tT3, tT4, fT3and tT3/fT3 (P < 0.05) were still significant in the adjusted model. And it is worth noting that there is an approximately L-shaped nonlinear relationship between ln(klotho) and fT3,tT3 with a cut-off point of 6.697 (P-non-linear < 0.05). The stratification analysis showed gender and iodine level differences in the relationship between serum Klotho levels and thyroid hormones. CONCLUSION: There is an L-shaped nonlinear relationship between ln(klotho) and fT3, tT3, suggesting that klotho could be involved in the physiological regulation of thyroid function.

Relationship between body fat ratio and inflammatory markers in a Chinese population of adult male smokers.

Objective: To explore the correlation between changes in the body fat ratio (BFR) and peripheral blood inflammatory markers according to smoking status in the adult Chinese male population. Methods: A total of 865 participants (aged 20-70 years) were included. All participants underwent a physical health examination at Xiguzhou Central Hospital between October 2015 and July 2016, including measurements of body mass index (BMI), BFR, white blood cell [WBC] count, and neutrophil-lymphocyte ratio [NLR]. Results: WBCs count and NLR were significantly higher in adult male smokers than in non-smokers (P = 0.00). According to the BFR stratification analysis, WBC count and NLR significantly increased in accordance with BFR (P = 0.00). This finding remained significant after adjusting for relevant confounding factors (P < 0.05). Two-factor stratified analysis of smoking status and BFR showed that WBC count and NLR in the smoking population were higher than in nonsmokers, regardless of BFR. The interaction model showed that BFR and smoking status affected WBC count and NLR changes (P < 0.05). A significant positive correlation was found between WBC count, NLR, and BFR in adult male smokers; however, there was no significant correlation with BMI. There was an interaction between smoking and BFR, both of which synergistically affected changes in inflammatory markers, including WBC count and NLR. Conclusion: WBC count and NLR of smokers with a high BFR were significantly higher than those of nonsmokers with a low BFR. It is important to provide evidence-based medical evidence for social tobacco control and to reduce BFR.

Fanconi syndrome induced by the long-term use of tenofovir disoproxil fumarate: a case report and literature review.

We present the case of a woman of 50 years of age who experienced widespread bone pain along with digestive symptoms, including nausea and vomiting. She had been prescribed tenofovir disoproxil fumarate (TDF) tablets for the treatment of hepatitis B. Laboratory testing revealed low circulating phosphorus and potassium concentrations and acidosis. A whole-body bone scan revealed abnormal bone metabolism. Rheumatologic and urologic conditions were ruled out, and therefore TDF-induced Fanconi syndrome (FS) and related bone pain was diagnosed. After the TDF was discontinued, the patient's symptoms and laboratory indices significantly improved. In this manuscript, we highlight the clinical manifestations of and laboratory test results associated with FS and summarize the cases of TDF-induced FS reported on PubMed between 2013 and 2022 to improve understanding of FS.

Epidemiological and transcriptome data identify potential key genes involved in iron overload for type 2 diabetes.

BACKGROUND: Many previous studies have reported the association between iron overload (IO) and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanism is not clear. METHODS: Epidemiological data from the National Health and Nutrition Examination Survey 2017-2018 (NHANES) was used to systematically explore the association between IO and diabetes. Furthermore, transcriptome data from Gene Expression Omnibus (GEO) were analyzed using bioinformatics methods to explore the underlying functional mechanisms at the molecular level. RESULTS: Data from NHANES showed a "W" shape relationship between serum iron (frozen) and the risk of diabetes (P < 0.001) as well as a "∧" shape correlation between serum unsaturated iron binding capacity (UIBC) and the risk of diabetes (P = 0.007). Furthermore, the serum iron (frozen) was positively associated with fasting plasma glucose and HOMAB (P < 0.05), and UIBC was positively associated with fasting insulin (P < 0.05). Transcriptome data showed that two IO-related genes [Transferrin receptor (TFRC) and Solute carrier family-11 member-2 (SLC11A2)] were down-regulated in T2DM. The correlation analysis showed that expression levels of TFRC and SLC11A2 were significantly and positively correlated with genes involved in insulin secretion (P < 0.05). Protein-protein interaction network analysis showed that TFRC and SLC11A2 interacted with four key genes, including VAMP2, HIF1A, SLC2A1, and RAB11FIP2. CONCLUSION: We found that IO status was associated with increased FPG and aggravated HOMAB, and two IO-related genes (TFRC and SLC11A2) might induce the occurrence of T2DM by influencing insulin secretion, which provides potential therapeutic targets for T2DM patients.

Evaluation of the healing potential of short-term ozone therapy for the treatment of diabetic foot ulcers.

Background: The availability of research on short-term ozone therapy for diabetic foot ulcers (DFUs) is limited, and even when it is accessible, it mainly comprises of basic analysis conducted during long-term ozone therapy. This study was to evaluate the efficacy of short-term ozone therapy in promoting wound healing in DFUs. Methods: A retrospective analysis was conducted on 89 patients with type 2 diabetes complicated by DFUs. The patients were divided into two groups: ozone therapy group (n=41) and control group (n=48). Wound condition, change of bacterial types, changes in inflammatory indicators (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and procalcitonin [PCT]), vascular endothelial growth factor (VEGF), cytokines [Interleukin 6 (IL-6) and tumor necrosis factor-α(TNF-α)], and oxidative stress levels (superoxide dismutase [SOD], malondialdehyde [MDA], and total antioxidant capacity [T-AOC]) were observed pre-treatment and after 1 week. After a 12-week of follow-up, wound healing rate, amputation rate, inpatient day, duration of antibiotics, reinfection rate, incidence of new ulcers, readmission rate, and reoperation rate, and cumulative wound healing rate using Kaplan-Meier curves were assessed. Results: After 1 week of treatment, the ozone therapy group showed higher VEGF, SOD, and T-AOC levels compared to the control group (P<0.05), while CRP, PCT, ESR, IL-6, TNF-α, MDA levels and bacterial types were lower (P<0.05). The ozone therapy group had a higher wound healing rate after a 12-week follow-up (P<0.05). Kaplan-Meier curves indicated a higher cumulative wound healing rate in the ozone therapy group (P<0.05). Additionally, the ozone therapy group had lower inpatient day, duration of antibiotics, reinfection rate, and readmission rate compared to the control group (P<0.05). Conclusion: Short-term ozone therapy is effective in promoting wound healing in DFUs by reducing inflammation, increasing growth factor levels, improving oxidative stress status, shortening healing time, and improving long-term prognosis. These findings suggest the potential of short-term ozone therapy as a valuable treatment modality for DFUs.

Decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus.

The discovery of a large number of small pulmonary nodules and early diagnosis of lung cancer in the diabetic patients prompt us to re-examine the relationship between diabetes and the occurrence and development of lung cancer. The aim of this study was to explore the underlying metabolites changes in diabetes with NSCLC or benign nodule patients, and further to investigate the association of serum IGF-1 level and differentially expressed metabolites (DEMs). An untargeted metabolomics method was used to detect the changes of metabolism in diabetic patients with NSCLC on the platform of HR-MS. Serum level of IGF-1 was measured by ELISA. The patients were divided to three groups, DM, DLB (nodule), and DLC (cancer). we have identified numerous DEMs, which include amino acid, choline, and fatty acid derivatives. Further analysis of the involved metabolic pathways suggested that linoleate metabolism, tryptophan metabolism, histidine metabolism, putative anti-Inflammatory metabolites formation from EPA, and arachidonic acid metabolism were considered to be the most significant metabolic pathways between groups. Networks analysis suggested that a series of metabolites were associated with serum IGF-1among the three groups, which can be divided into 6 categories. Nine metabolites have been identified as the main DEMs among the DLC, DLB, and DM groups. In conclusion, metabolomics is a powerful and promising tool for the cancer risk evaluation in diabetic patients. Our results suggest that decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus.

Lifestyle in adulthood can modify the causal relationship between BMI and islet function: using Mendelian randomization analysis.

BACKGROUND: Body mass index was intimately associated with islet function, which was affected by various confounding factors. Among all methods of statistical analysis, Mendelian randomization best ruled out bias to find the causal relationship. In the present study, we explored the relationship between 13 East Asian body mass index-related genes reported previously and islet function using the Mendelian randomization method. METHODS: A total of 2892 participants residing in northern China were enrolled. Anthropological information, such as sex, age, drinking status, smoking status, weight, height and blood pressure, was recorded for all participants. Fasting glucose and insulin were detected, and the insulin sensitivity index was calculated. 13 single nucleotide polymorphismss in East Asian body mass index -related genes were analysed with the ABI7900HT system. RESULTS: Five genetic locus mutations, CDKAL1, MAP2K5, BDNF, FTO and SEC16B, were found to be associated with body mass index and were used to estimate the genetic risk score. We found that the genetic risk score was negatively associated with the insulin sensitivity index. Even after adjusted of confounding factors, the relationship showed statistical significance. A subsequent interaction effect analysis suggested that the negative relationship between the genetic risk score and insulin sensitivity index no longer existed in the nondrinking population, and smokers had a stronger negative relationship than nonsmokers. CONCLUSION: We found a negative causal relationship between body mass index-related genetic locus mutations and insulin resistance, which might be increased by acquired lifestyle factors, such as drinking and smoking status.

A meta-analysis of circulating microRNAs in the diagnosis of papillary thyroid carcinoma.

BACKGROUND: Aim of this meta-analysis was to evaluate the overall diagnostic value of circulating mini miRNAs for papillary thyroid carcinoma (PTC) and to find the possible molecular marker with higher diagnostic value for PTC. METHODS: We searched the Pubmed, Cochrane and Embase database until June 2020. We selected relevant literatures associated with the diagnosis of PTC with circulating miRNAs. The number of cases in experimental group and the control group, sensitivity and specificity could be extracted from the literatures. RESULTS: We got 9 literatures including 2114 cases of PTC. Comprehensive sensitivity was 0.79, comprehensive specificity was 0.82, positive likelihood ratio was 4.3, negative likelihood ratio was 0.26, diagnostic advantage ratio was 16. The summary receiver operating characteristic curve was drawn and the Area Under the Curve was 0.87. CONCLUSIONS: Circulating microRNAs may be promising molecular markers for the diagnosis of papillary thyroid carcinoma. Combined detection of certain serum microRNAs can improve the diagnostic accuracy of papillary thyroid carcinoma. Especially MiR-222 and miR-146b may be prime candidates for the diagnosis of PTC in Asian population.

Enrichment and Quantitative Determination of Free 3,5- Diiodothyronine, 3',5'-Diiodothyronine, and 3,5-Diiodothyronamine in Human Serum of Thyroid Cancer by Covalent Organic Hyper Cross-linked Poly-ionic Liquid.

The incidence of thyroid cancer is increasing worldwide. So far, still no non-invasive clinical test biomarkers were developed for the diagnosis of thyroid cancer. The diiodothyronines (T2s) are precursors and metabolites of thyroid hormone (T4). Some reports predict that T2s may be associated with several thyroid diseases, especially the thyroid cancer. Detecting free T2s in human serum may help the diagnosis of thyroid cancer. However, few works have reported the detection of T2s due to their trace amounts. Here we developed a novel hyper organic cross-linked poly ionic liquid (PIL) material for the enrichment of three main compounds in T2s family, including 3,5- diiodothyronine (3,5-T2), 3',5'-diiodothyronine (3',5'-T2), and 3,5-diiodothyronamine (3,5-T2AM). This PIL material provided specific enrichment superiority for three T2s. After enrichment, the signal intensity of 3,5-T2, 3',5'-T2, and 3,5-T2AM increased 14, 132 and 1.6 folds, respectively, with LOQ of 76, 87, and 107 fM, respectively. Finally, we successfully applied PIL material coupled with HPLC-ESI-MS/MS in enrichment and quantitative determination of free 3,5-T2, 3',5'-T2, and 3,5-T2AM in human serum of 45 thyroid cancer patients and 15 healthy people. We also used free thyroid hormone (FT4) as the calibration reference to eliminate individual differences. We found that the levels of 3,5-T2 (P < 0.001), and 3',5'-T2 (P = 0.001) in patients with thyroid cancer were significantly higher than those in healthy people. Additionally, we further investigated the power of different T2 thyroid hormones divided FT4 to classify thyroid cancer patients and healthy people. And 3,5-T2/FT4 had the highest classification performance for discriminating thyroid cancer patients from healthy people at certain threshold, indicating that 3,5-T2/FT4 in human serum can act as potential biomarkers for "non-invasive" clinical diagnosis of thyroid cancer.

Distinct Prognostic Values of the mRNA Expression of Glucose Transporters in Non-Small Cell Lung Cancer.

Glucose is the major source of energy for cells. Facilitative glucose transporters (GLUTs) mediate the transport of glucose into cells. The GLUT family has 14 members that are expressed in different tissues of the body and play essential roles in sustaining the energy demand. However, the prognostic value of the majority of GLUTs in lung cancer remains elusive and should be further evaluated in clinical studies. Thus, we investigated the prognostic data of GLUTs in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients through the "Kaplan-Meier (KM) plotter" database. In the current study, we found that 12 members of the GLUTs family were significantly associated with prognosis of LUAD patients, but GLUT8 was not. High expression levels of GLUT10, GLUT12, and GLUT13 were significantly associated with better overall survival (OS) in LUAD, while the other 9 members were associated with worse OS. However, GLUT family members were not correlated with OS in LUSC, although high mRNA expression level of GLUT1 tend to show an inferior OS (P=0.057). The prognostic value of GLUTs according to smoking status was also assessed. In conclusion, our study provides new insights into the prognostic values of GLUT members in LUAD, but the molecular mechanisms by which GLUTs contribute to disease aggression and the different functional roles of GLUT members need further study.

Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition).

In recent years, as living standards have continued to improve, the number of diabetes patients in China, along with the incidence of complications associated with the disease, has been increasing. Among these complications, diabetic foot disease is one of the main causes of disability and death in diabetic patients. Due to the differences in economy, culture, religion and level of medical care available across different regions, preventive and treatment methods and curative results for diabetic foot vary greatly. In multidisciplinary models built around diabetic foot, the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology. In 2019, under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society, the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition) was established with the participation of scholars from the specialist areas of endocrinology, burn injury, vascular surgery, orthopedics, foot and ankle surgery and cardiology. Drawing lessons from diabetic foot guidelines from other countries, this guide analyses clinical practices for diabetic foot, queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China. This paper begins with assessments and diagnoses of diabetic foot, then describes treatments for diabetic foot in detail, and ends with protections for high-risk feet and the prevention of ulcers. This manuscript covers the disciplines of internal medicine, surgical, nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with a rapidly increasing incidence globally. Bioinformatics analyses suggested that SHCBP1 (SHC SH2 Domain-Binding Protein 1) was significantly up-regulated in PTC tumor tissues, which was further confirmed by immunohistochemical staining and qPCR analyses in Xuzhou cohort. Moreover, the results indicated that the mRNA level of SHCBP1 was negatively associated with patients' disease-free survival rate, and further analysis reveals that patients with high SHCBP1 expression tend to have more lymph node metastasis. Afterward, MTT, colony formation, cell-cycle assay, FACS apoptosis assay, invasion, migration, as well as scratch assay were performed to study the phenotypes change of PTC cells after knocking down SHCBP1. The in vivo subcutaneous tumor model was developed to study the proliferation ability of PTC cells after SHCBP1 knockdown. We show that knock down of SHCBP1 significantly inhibits PTC cell proliferation, cell cycle, invasion and migration in vivo and in vitro. Western blot and qRT-PCR showed that knockdown of SHCBP1 could significantly reduce MYC, KLF4, CD44, ITGA6, ITGB1, ITGB5, and COL4A2 expression at both RNA and protein levels, which indicated that SHCBP1 might be involved in PTC carcinogenesis and progression through targeting formation of integrin and collagen and cell stemness pathways, and can be a potential diagnosis biomarker and therapeutic target for PTC.