The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Unraveling the pesticide-diabetes connection: A case-cohort study integrating Mendelian randomization analysis with a focus on physical activity's mitigating effect.

BACKGROUND AND AIMS: There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. METHODS: A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. RESULTS: After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. CONCLUSIONS: Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure.

Characteristics of after-discharges following compound muscle action potential or F-wave in primary peripheral nerve hyperexcitability syndrome.

INTRODUCTION/AIMS: F-wave testing frequently reveals after-discharges of varied morphologies in patients with primary peripheral nerve hyperexcitability syndrome (PNHS), although reports are scant. This study aimed to explore the morphological characteristics of the after-discharges during F-wave tests in PNHS, and to assess the association between after-discharges and the disease classification. METHODS: We conducted a retrospective analysis of patients diagnosed with PNHS between 2014 and 2022. The morphological characteristic and duration of after-discharges during F-wave tests were analyzed. After-discharges in the Morvan syndrome group were compared with those in non-Morvan group, and between groups with positive or negative voltage-gated potassium channel (VGKC) complex antibodies. RESULTS: Twenty-nine patients were included in the study, of which 25 exhibited after-discharges. All after-discharges in Morvan patients occurred following compound muscle action potential (CMAP). In non-Morvan patients, after-discharges occurred following F-wave (32%) and CMAP (47%). The durations of after-discharges following CMAP were significantly prolonged in Morvan (54.2 ± 18.8 ms) compared to non-Morvan patients (34.5 ± 15.0 ms). The majority of antibody-positive patients (18/20) exhibited after-discharges following CMAP, whereas 67% of antibody-negative patients (6/9) showed after-discharges following F-wave. DISCUSSION: The varying presentations of after-discharges, including their location (after CMAP or F-wave) and the duration of after-discharge can assist in clinically classifying PNHS.

Versatile Method of Engineering the Band Alignment and the Electron Wavefunction Hybridization of Hybrid Quantum Devices.

Hybrid devices that combine superconductors (S) and semiconductors (Sm) have attracted great attention due to the integration of the properties of both materials, which relies on the interface details and the resulting coupling strength and wavefunction hybridization. However, until now, none of the experiments have reported good control of the band alignment of the interface, as well as its tunability to the coupling and hybridization. Here, the interface is modified by inducing specific argon milling while maintaining its high quality, e.g., atomic connection, which results in a large induced superconducting gap and ballistic transport. By comparing with Schrödinger-Poisson calculations, it is proven that this method can vary the band bending/coupling strength and the electronic spatial distribution. In the strong coupling regime, the coexistence and tunability of crossed Andreev reflection and elastic co-tunneling-key ingredients for the Kitaev chain-are confirmed. This method is also generic for other materials and achieves a hard and huge superconducting gap in lead and indium antimonide nanowire (Pb-InSb) devices. Such a versatile method, compatible with the standard fabrication process and accompanied by the well-controlled modification of the interface, will definitely boost the creation of more sophisticated hybrid devices for exploring physics in solid-state systems.

DHODH Alleviates Heart Failure via the Modulation of CoQ-Related Ferroptotic Inhibition.

BACKGROUND: Heart failure (HF) is a clinical syndrome that seriously endangers human health and quality of life as the terminal stage of cardiovascular diseases. Ferroptosis as a new iron-dependent programmed cell death mode that is closely related to the occurrence and development of cardiovascular diseases. Dihydroorotate dehydrogenase (DHODH) has been found to play a crucial role in inhibiting ferroptosis and improving mitochondrial function, and its expression can be upregulated by estradiol (E2). Recent studies have found that DHODH can inhibit ferroptosis by reducing coenzyme Q (CoQ) to CoQH2. Therefore, this study aims to explore the effect of up-regulation of DHODH on the pathological hypertrophy and fibrosis of heart failure and its mechanisms. METHODS: The mouse heart failure model was established by transverse aortic constriction (TAC), surgery in mice. Two days after the operation, a subcutaneous injection of E2 or the same volume of sesame oil was given for 8 weeks. Then, the left ventricular systolic function related indicators of mice were measured by echocardiography, and the degree of myocardial fibrosis of mice was detected by histological analysis; the expression levels of heart failure markers were detected by quantitative polymerase chain reaction (q-PCR) and western blot (WB) analysis; the morphological changes of mitochondria in cardiac cells of mice were observed by transmission electron microscopy. Cell model were established by stimulating with phenylephrine for 96 hours. Ferroptosis markers were detected by kits and WB analysis. Mitochondrial function was verified by a JC-1 fluorescent probe, and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining. The knockdown results were detected by WB analysis after transfection of small interfering RNA (siRNA) of CoQ. Fer-1 was added as a positive control to verify the ferroptosis-related changes of myocardial cells. RESULTS: In the animal model, we found that E2 treatment alleviates TAC-induced cardiac hypertrophy and fibrosis and suppresses cardiomyocyte ferroptosis by promotes DHODH upregulation in murine cardiomyocytes. In the cell model, DHODH upregulation protects against phenylephrine-induced cardiomyocytes with failure. However, the effect on up-regulating DHODH was inhibited by transfection to down-regulate CoQ expression. CONCLUSIONS: The up-regulation of DHODH could effectively ameliorate the manifestations of heart failure such as myocardial hypertrophy and fibrosis in mice after TAC surgery, inhibit ferroptosis of cardiac myocytes, and ameliorate mitochondrial function. The mechanism involves CoQ-related biological processes.

Effects of artificial light with different spectral compositions on refractive development and matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2 expression in the sclerae of juvenile guinea pigs.

Artificial light can affect eyeball development and increase myopia rate. Matrix metalloproteinase 2 (MMP-2) degrades the extracellular matrix, and induces its remodeling, while tissue inhibitor of matrix MMP-2 (TIMP-2) inhibits active MMP-2. The present study aimed to look into how refractive development and the expression of MMP-2 and TIMP-2 in the guinea pigs' remodeled sclerae are affected by artificial light with varying spectral compositions. Three weeks old guinea pigs were randomly assigned to groups exposed to five different types of light: natural light, LED light with a low color temperature, three full spectrum artificial lights, i.e. E light (continuous spectrum in the range of ~390-780 nm), G light (a blue peak at 450 nm and a small valley 480 nm) and F light (continuous spectrum and wavelength of 400 nm below filtered). A-scan ultrasonography was used to measure the axial lengths of their eyes, every two weeks throughout the experiment. Following twelve weeks of exposure to light, the sclerae were observed by optical and transmission electron microscopy. Immunohistochemistry, Western blot and RT-qPCR were used to detect the MMP-2 and TIMP-2 protein and mRNA expression levels in the sclerae. After four, six, eight, ten, and twelve weeks of illumination, the guinea pigs in the LED and G light groups had axial lengths that were considerably longer than the animals in the natural light group while the guinea pigs in the E and F light groups had considerably shorter axial lengths than those in the LED group. Following twelve weeks of exposure to light, the expression of the scleral MMP-2 protein and mRNA were, from low to high, N group, E group, F group, G group, LED group; however, the expression of the scleral TIMP-2 protein and mRNA were, from high to low, N group, E group, F group, G group, LED group. The comparison between groups was statistically significant (p<0.01). Continuous, peaks-free or valleys-free artificial light with full-spectrum preserves remodeling of scleral extracellular matrix in guinea pigs by downregulating MMP-2 and upregulating TIMP-2, controlling eye axis elongation, and inhibiting the onset and progression of myopia.

Qualitative and quantitative assessment of non-clear cell renal cell carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Non-clear cell renal cell carcinoma (nccRCC) represents a rare form of renal cell carcinoma (RCC) in the clinic. It is now understood that contrast-enhanced ultrasound (CEUS) exhibits diverse manifestations and can be prone to misdiagnosis. Therefore, summarizing the distinctive features of contrast-enhanced ultrasonography is essential for differentiation from ccRCC. OBJECTIVE: This study aims to evaluate the diagnostic efficacy of qualitative and quantitative CEUS in diagnosing nccRCC to enhance our understanding of this condition. METHODS: We conducted a retrospective analysis of 21 patients with confirmed nccRCC following surgery and assessed the characteristic conventional ultrasound and CEUS imaging features. The paired Wilcoxon signed-rank sum test was employed to compare differences in CEUS time-intensity curve (TIC) parameters between the lesions and the normal renal cortex. RESULTS: Routine ultrasound revealed the following primary characteristics in the 21 nccRCC cases: hypoechoic appearance (10/21, 47.6%), absence of liquefaction (18/21, 66.7%), regular shape (19/21, 90.5%), clear boundaries (21/21, 100%), and absence of calcification (17/21, 81%). Color Doppler flow imaging (CDFI) indicated a low blood flow signal (only 1 case of grade III). Qualitative CEUS analysis demonstrated that nccRCC predominantly exhibited slow progression (76.1%), fast washout (57%), uniformity (61.9%), low enhancement (71.5%), and ring enhancement (61.9%). Quantitative CEUS analysis revealed that parameters such as PE, WiAUC, mTTI, WiR, WiPI, WoAUC, WiWoAUC, and WOR in the lesions were significantly lower than those in the normal renal cortex (Z=-3.980, -3.563, -2.427, -3.389, -3.980, -3.493, -3.528, -2.763, P < 0.001, < 0.001, = 0.015, = 0.001, < 0.001, < 0.001, < 0.001, = 0.006). However, there were no significant differences in RT, TTP, FT, or QOF (all P > 0.05). CONCLUSION: nccRCC exhibits distinctive CEUS characteristics, including slow progression, fast washout, low homogeneity enhancement, and ring enhancement, which can aid in distinguishing nccRCC from ccRCC.

An automated method for assessing condyle head changes in patients with skeletal class II malocclusion based on Cone-beam CT images.

OBJECTIVES: Currently, there is no reliable automated measurement method to study the changes in the condylar process after orthognathic surgery. Therefore, this study proposes an automated method to measure condylar changes in patients with skeletal class II malocclusion following surgical-orthodontic treatment. METHODS: Cone-beam CT (CBCT) scans from 48 patients were segmented using the nnU-Net network for automated maxillary and mandibular delineation. Regions unaffected by orthognathic surgery were selectively cropped. Automated registration yielded condylar displacement and volume calculations, each repeated three times for precision. Logistic regression and linear regression were used to analyse the correlation between condylar position changes at different time points. RESULTS: The Dice score for the automated segmentation of the condyle was 0.971. The intraclass correlation coefficients (ICCs) for all repeated measurements ranged from 0.93 to 1.00. The results of the automated measurement showed that 83.33% of patients exhibited condylar resorption occurring six months or more after surgery. Logistic regression and linear regression indicated a positive correlation between counterclockwise rotation in the pitch plane and condylar resorption (P < .01). And a positive correlation between the rotational angles in both three planes and changes in the condylar volume at six months after surgery (P ≤ .04). CONCLUSIONS: This study's automated method for measuring condylar changes shows excellent repeatability. Skeletal class II malocclusion patients may experience condylar resorption after bimaxillary orthognathic surgery, and this is correlated with counterclockwise rotation in the sagittal plane. ADVANCES IN KNOWLEDGE: This study proposes an innovative multi-step registration method based on CBCT, and establishes an automated approach for quantitatively measuring condyle changes post-orthognathic surgery. This method opens up new possibilities for studying condylar morphology.

Associations of serum glucocorticoid levels on hypertension and blood pressure-related indicators: a nested case-control study in rural China.

BACKGROUND: The relationship between glucocorticoids and hypertension has shown inconsistent findings in previous studies. To address this, our study employed a nested case-control design in rural areas to further investigate the association between serum glucocorticoid levels and hypertension, and blood pressure-related indicators. METHODS: This study employed a nested case-control design, involving 560 pairs of hypertensive cases and matched controls. The concentrations of serum cortisol (F), cortisone (E) and 11-deoxycortisol (S) were determined using liquid chromatography-tandem mass spectrometry. We employed various methods, including generalized linear model (GLM), conditional logistic regression model, restricted cubic spline regression, subgroup analysis, interaction, and joint effects, with adjustments for multiple covariates to analyze the relationships between glucocorticoids, hypertension, and blood pressure-related indicators. RESULTS: After multivariable adjustments, ln-F, ln-F/E, and ln-S were positively associated with SBP, DBP, pulse pressure (PP), and mean arterial pressure (MAP), while ln-E was negatively associated with DBP and MAP ( P  < 0.05). Interestingly, ln-S showed no statistically significant association with hypertension prevalence ( P  > 0.05), whereas ln-F and ln-F/E were positively associated with it ( P  < 0.05). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.153 (1.011-1.315) for ln-F and 2.072 (1.622-2.645) for ln-F/E, respectively. In contrast, ln-E exhibited a negative association with hypertension prevalence (adjusted OR = 0.837, 95% CI 0.714-0.982). Moreover, a significant association was observed between the combined use of high-dose F/E and high-dose S with hypertension prevalence (adjusted OR = 3.273, 95% CI 2.013-5.321). Blood pressure indicators and hypertension prevalence significantly increased with elevated serum F and F/E concentrations ( P  < 0.05). Interaction analysis further revealed that among women, the positive association between F/E and hypertension prevalence was more pronounced than in men ( P  < 0.05), and S exhibited a more significant positive association with hypertension prevalence in the overweight population ( P  < 0.05). CONCLUSION: Serum F/E and S levels demonstrated positive associations with hypertension and blood pressure-related indicators, and their combined influence exhibited a synergistic effect on hypertension. Notably, F, F/E, and S were associated with heightened hypertension risk, warranting particular attention in women and overweight populations.

The MYB family and their response to abiotic stress in ginger (Zingiber officinale Roscoe).

BACKGROUND: Zingiber officinale Roscoe, colloquially known as ginger, is a crop of significant medicinal and culinary value that frequently encounters adversity stemming from inhospitable environmental conditions. The MYB transcription factors have garnered recognition for their pivotal role in orchestrating a multitude of plant biological pathways. Nevertheless, the enumeration and characterization of the MYBs within Z. officinale Roscoe remains unknown. This study embarks on a genome-wide scrutiny of the MYB gene lineage in ginger, with the aim of cataloging all ZoMYB genes implicated in the biosynthesis of gingerols and curcuminoids, and elucidating their potential regulatory mechanisms in counteracting abiotic stress, thereby influencing ginger growth and development. RESULTS: In this study, we identified an MYB gene family comprising 231 members in ginger genome. This ensemble comprises 74 singular-repeat MYBs (1R-MYB), 156 double-repeat MYBs (R2R3-MYB), and a solitary triple-repeat MYB (R1R2R3-MYB). Moreover, a comprehensive analysis encompassing the sequence features, conserved protein motifs, phylogenetic relationships, chromosome location, and gene duplication events of the ZoMYBs was conducted. We classified ZoMYBs into 37 groups, congruent with the number of conserved domains and gene structure analysis. Additionally, the expression profiles of ZoMYBs during development and under various stresses, including ABA, cold, drought, heat, and salt, were investigated in ginger utilizing both RNA-seq data and qRT-PCR analysis. CONCLUSION: This work provides a comprehensive understanding of the MYB family in ginger and lays the foundation for the future investigation of the potential functions of ZoMYB genes in ginger growth, development and abiotic stress tolerance of ginger.

High-frame-rate contrast-enhanced ultrasound to differentiate between clear cell renal cell carcinoma and angiomyolipoma.

BACKGROUND: To investigate the diagnostic efficacy of high-frame-rate contrast-enhanced ultrasound (H-CEUS) in differentiating between clear cell renal cell carcinoma (CCRCC) and angiomyolipoma (AML). METHODS: A retrospective study was performed on the clinical data of 79 patients diagnosed with CCRCC and 31 patients diagnosed with AML at the First Affiliated Hospital of Nanchang University between October 2022 and December 2023. Conventional ultrasound (US) and H-CEUS examinations were conducted on all patients prior to surgery, dynamic images were recorded from the US, and the qualitative and quantitative parameters of H-CEUS were collected. The t-test, χ² test and non-parametric Mann-Whitney test were employed to assess differences in clinical data, US characteristics, and qualitative and quantitative parameters of H-CEUS between the CCRCC and AML groups. The independent risk factors of CCRCC were identified using binary logistic regression. The receiver operator characteristic (ROC) curve was constructed to evaluate the diagnostic effectiveness of clinical + US and H-CEUS in differentiating between CCRCC and AML. RESULTS: The CCRCC group and the AML group exhibited significant differences in patient gender, operation mode, nodular echo, and nodule blood flow (χ²=11.698, -, -,=10.582; P<0.001, <0.001, <0.001, and = 0.014, respectively). In addition, the H-CEUS qualitative analysis demonstrated significant differences between the AML group and the CCRCC group with respect to enhancement mode, regression mode, peak intensity, enhancement uniformity, no enhancement, and presence or absence of pseudocapsule (χ²=41.614, -, -, = 2.758, = 42.099, -; P<0.001, <0.001, <0.001, 0.097, <0.001, and <0.001, respectively). The Arrival time (AT) in the CCRCC group was significantly shorter than that in the AML group, as determined by quantitative analysis of H-CEUS (Z=-3.266, P = 0.001). Furthermore, the Peak intensity (PI), Ascent slope (AS), and The area under the curve (AUC) exhibited significantly higher values in the CCRCC group compared to the AML group (Z=-2.043,=-2.545,=-3.565; P = 0.041, = 0.011, and <0.001, respectively). Logistic regression analysis indicated that only gender, nodule echo, the pseudocapsule, AS, and AUC of H-CEUS were independent risk factors of CCRCC. The ROC curve revealed that combining gender and nodule echo yielded a sensitivity of 92.4%, specificity of 64.5%, and an AUC of 0.847 in distinguishing between CCRCC and AML. When combining the H-CEUS parameters of pseudocapsule, AS, and AUC, the sensitivity, specificity, and AUC for distinguishing between CCRCC and AML were 84.8%, 96.8%, and 0.918, respectively. No statistically significant difference was observed in the diagnostic effectiveness of the two methods (Z=-1.286, P = 0.198). However, H-CEUS demonstrated better AUC and specificity. CONCLUSIONS: H-CEUS enhances the sensitivity and specificity of differentiating between CCRCC and AML by improving the temporal resolution, offering a more precise diagnostic foundation for identifying the most appropriate therapy for patients.

New findings on the risk of hypertension from organophosphorus exposure under different glycemic statuses: The key role of lipids?

BACKGROUND AND OBJECTIVE: Considering the widespread use of organophosphorus pesticides (OPs) and the global prevalence of hypertension (HTN), as well as studies indicating that different glycemic statuses may respond differently to the biological effects of OPs. Therefore, this study, based on the Henan rural cohort, aims to investigate the association between OPs exposure and HTN, and further explores whether lipids mediate these associations. METHODS: We measured the plasma levels of OPs in 2730 participants under different glycemic statuses using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). A generalized linear model, Quantile g-computation (QGC), adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) models were used to assess the impact of OPs exposure on HTN, with least absolute shrinkage and selection operator (LASSO) penalty regression identifying main OPs. Mediation models were used to evaluate the intermediary role of blood lipids in the OPs-HTN relationship. RESULTS: The detection rates for all OPs were high, ranging from 76.35 % to 99.17 %. In the normal glucose tolerance (NGT) population, single exposure models indicated that malathion and phenthoate were associated with an increased incidence of HTN (P-FDR < 0.05), with corresponding odds ratios (ORs) and 95 % confidence intervals (CIs) of 1.624 (1.167,2.260) and 1.290 (1.072,1.553), respectively. QGC demonstrated a positive association between OP mixtures and HTN, with malathion and phenthoate being the primary contributors. Additionally, the AENET model's Exposure Response Score (ERS) suggested that the risk of HTN increases with higher ERS (P < 0.001). Furthermore, BKMR revealed that co-exposure to OPs increases HTN risk, with phenthoate having a significant impact. Furthermore, triglycerides (TG) mediated 6.55 % of the association between phenthoate and HTN. However, no association was observed in the impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) populations. CONCLUSIONS: Our findings suggest that in the NGT population, OPs may significantly contribute to the development of HTN, proposing TG as a potential novel target for HTN prevention.

Inflammatory markers and androstenedione modify the effect of serum testosterone on obesity among men: Findings from a Chinese population.

BACKGROUND: Few studies are available on the relationship of androstenedione with inflammation and obesity and the effect of androstenedione and inflammation on the association between testosterone and obesity. This study intended to examine the mediation effect of inflammatory markers on the association of testosterone with obesity and the moderation effect of androstenedione on the association of testosterone with inflammation and obesity in Chinese rural men. MATERIALS AND METHODS: This cross-sectional research enrolled 2536 male rural inhabitants from the Henan Rural Cohort study. The serum concentrations of testosterone and androstenedione were determined by liquid chromatography-tandem mass spectrometry. Linear and logistic regression were used to examine the relationships between testosterone, inflammatory markers, and obesity. Mediation and moderation analyses were carried out to evaluate the potential effects of inflammatory markers on the relationship between testosterone and obesity, as well as androstenedione on the relationships of testosterone with inflammation and obesity. RESULTS: After adjusting for confounding factors, the results showed that testosterone and androstenedione were negatively related to obesity, and inflammatory markers were positively associated with obesity. Besides, testosterone and androstenedione were negatively associated with inflammatory markers. Mediation analysis showed that white blood cell, neutrophil, monocyte, and high-sensitivity C-reactive protein had mediating effects on the association between testosterone and obesity. The most vital mediator was high-sensitivity C-reactive protein, and its proportion of the effect was 11.02% (defined by waist circumference), 11.15% (defined by waist-to-hip ratio), 12.92% (defined by waist-to-height ratio), and full mediating effect (defined by body mass index). Moreover, androstenedione played negative moderation effects on the associations of testosterone with inflammation and obesity. CONCLUSION: Inflammatory markers and androstenedione were first found to have modifying effects on the association of testosterone with obesity. Higher levels of testosterone and androstenedione could reduce the inflammation level and risk of obesity, indicating their potential roles in the prevention and treatment of chronic diseases.

Combined effects of organochlorine pesticides on type 2 diabetes mellitus: Insights from endocrine disrupting effects of hormones.

Association between organochlorine pesticides (OCPs) exposure and type 2 diabetes mellitus (T2DM) remains contradictory, and the evidence is mostly focused on a single exposure. Here, we assessed the associations between individual and combined OCPs exposure and T2DM, and explored the underlying mechanism of sex hormones and the methylation levels of sex hormone receptors in above associations. A case-control study with 1812 participants was performed. Gas chromatography mass spectrometry, liquid chromatography-tandem mass spectrometry, and pyrosequencing were used to measure plasma OCPs, serum sex hormones, and whole blood methylation levels of sex hormone receptors, respectively. Generalized linear models were used to analyze the relationships between OCPs, sex hormones, the methylation levels of sex hormone receptors, and T2DM. Quantile based g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined OCPs exposure. The roles of sex hormones and the methylation levels of their receptors were evaluated by moderating mediation models. After adjusting for covariates, each unit (2.718 ng/ml) increase in p,p'-DDE was associated with a higher risk of T2DM in males (odds ratio (OR) and 95% confidence interval (CI): 1.066 (1.023, 1.112)). QGC and BKMR showed a positive combined effect in the associations of OCPs mixtures on T2DM among premenopausal females, and positive effects but not statistically significant among males and postmenopausal females. p,p'-DDE was the largest contributor for the positive associations. Furthermore, testosterone mediated 21.149% of the associations of p,p'-DDE with T2DM moderated by the androgen receptor methylation (ARm) located in CpG island 1. Individual and mixtures of OCPs exposure were positively linked to elevated risk of T2DM. Testosterone and ARm may participate in the related processes of OCPs with T2DM, providing new insights into the adverse endocrine effects caused by OCPs and specific pathways for the etiology and control of diabetes.

Development and Validation of Nomograms to Predict Risk and Prognosis in Salivary Gland Carcinoma Patient with Distant Metastases.

Background: Salivary gland carcinoma (SGC) patients with distant metastasis (DM) are rare, and understanding this disease is insufficient. Nomograms can predict the prognostic probability of patients, while few studies have examined diagnostic and prognostic factors in SGC patients with DM. The purpose of this study was to establish and validate the risk and prognostic nomograms of SGC patients with DM. Methods: Based on the SEER database, we analyzed the data of SGC patients between 2004 and 2015. Logistic regression analyses and Cox proportional hazards regression analyses were used to identify risk and prognostic factors for DM in SGC patients. Based on the Akaike information criterion (AIC) value and likelihood ratio test, the best-fitting model was selected to build risk and prognostic nomograms, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and Kaplan-Meier (K-M) survival curves. ROC curves were also used to compare the nomograms with the American Joint Committee on Cancer (AJCC) staging system. Results: 7418 SGC patients were included in the study, and 307 (4.14%) of them were diagnosed with DM. This study identified that there are variables (age ≥ 80, no-parotid gland primary site, histologic type of mucoepidermoid carcinoma and squamous cell carcinoma, T stage ≥ T2, N staged ≥ N1, histologic grade ≥ III, and tumor size ≥ 41 mm) associated with the occurrence of DM in SGC patients. Therefore, we constructed diagnostic and prognostic nomograms after incorporating these variables. ROC curves illustrated the better predictive efficacy of 2 nomograms over the AJCC staging system. DCA curves, calibration curves, and K-M survival curves showed that 2 nomograms can accurately predict the occurrence and prognosis of DM among SGC patients in training and validation sets. Conclusion: It was shown that the nomograms were highly discriminative in predicting the diagnosis and prognosis of SGC patients with DM, and could identify high-risk patients, thereby providing SGC patients with individualized treatment plans.

Case report: Mononeuropathy multiplex of extranodal natural killer/T-cell lymphoma misdiagnosed as systemic vasculitis.

Background: Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract. Case presentation: We encountered an ENKTL patient who presented with purpura-like rashes and foot drops as initial symptoms and later developed other peripheral nerve involvement. The nerve conduction study of both the motor nerve and the sensory nerve showed axonal damage resembling mononeuropathy multiplex. Although the initial response to steroids was encouraging, the patient's symptoms reappeared and aggravated. A biopsy of the abdominal subcutaneous fat tissue with additional immunohistochemistry revealed neoplastic NK/T lymphocytes. Conclusion: We reported the first case presented as mononeuropathy multiplex as the initial clinical manifestation in ENKTL patients. Lymphoma should be considered in the diagnosis of atypical mononeuropathy in multiplex patients.

Establishment of Ferroptosis-Associated Molecular Subtypes and Hub Genes Related to the Immune Microenvironment of Heart Failure.

BACKGROUND: Ferroptosis is a form of iron-dependent regulated cell death, and prior work has highlighted the potential utility of ferroptosis-inducing agents as tools to treat heart failure (HF). To date, however, no detailed examinations of the prognostic utility of ferroptosis-related genes (FRGs) in HF have been conducted. METHODS: We used established genomic identification of FRGs for total samples in the gene expression omnibus (GEO) database, screened for differentially expressed FRGs, performed protein-protein interaction analysis and functional analysis of HF immune microenvironment subtypes. Subsequently, we applied tools to calculate immune cell infiltration, compare immune cell, immune response genomic and HLA gene differences between subtypes, and perform candidate drug identification. Finally, preliminary in vivo validation of the screened central genes was performed in animal models. RESULTS: FRGs were compared between samples from HF and healthy control donors, revealing 62 of these genes to be differentially expressed as a function of HF status. HF patient-derived tissues exhibited significant changes in the expression of HLA genes, increase immune cell infiltration, and higher levels of other immune-related genes within the associated immune microenvironment. These FRGs were then leveraged to establish two different immune-related subtypes of HF based on clustering analysis results, after which these subtypes were characterized in further detail. Functional enrichment analyses revealed the identified differentially expressed genes to be enriched in key immune-related pathways including the primary immunodeficiency, natural killer cell-mediated cytotoxicity, FcϵRI signaling, and antigen processing and presentation pathways. The impact of the immune microenvironment was also explored through functional analyses, core gene analyses, and efforts to identify potential drug candidates for HF patients. Moreover, four key hub genes were identified as promising targets for therapeutic intervention in HF, including HDAC1, LNPEP, PSMA1, and PSMA6. Subsequent preclinical work in a mouse model system supported a potential role for HDAC1 as an important biomarker associated with the incidence of HF. CONCLUSIONS: To sum up, these results emphasize the importance of ferroptosis as a regulator of the HF-related immune microenvironment, highlighting viable avenues for the further study of molecular targets amenable to pharmacological intervention with the aim of treating this debilitating disease.

Association Analysis of Gut Microbiota and Prognosis of Patients with Acute Ischemic Stroke in Basal Ganglia Region.

Previous studies have implied the potential impact of gut microbiota on acute ischemic stroke (AIS), but the relationships of gut microbiota with basal ganglia region infarction (BGRI) and the predictive power of gut microbiota in BGRI prognosis is unclear. The aim of this study was to ascertain characteristic taxa of BGRI patients with different functional outcomes and identify their predictive value. Fecal samples of 65 BGRI patients were collected at admission and analyzed with 16s rRNA gene sequencing. Three-month functional outcomes of BGRI were evaluated using modified Rankin Scale (mRS), and patients with mRS score of 0-1 were assigned to good-BGRI group while others were assigned to poor-BGRI group. We further identified characteristic microbiota using linear discriminant analysis effect size, and receiver operating characteristic (ROC) curve was used to determine the predictive value of differential bacteria. According to the mRS score assessed after 3 months of stroke onset, 22 patients were assigned to poor-BGRI group, while 43 patients were assigned to good-BGRI group. Short chain fatty acids-producing bacteria, Romboutsia and Fusicatenibacter, were characteristic microbiota of the good-BGRI group, while pro-inflammatory taxa, Acetanaerobacterium, were characteristic microbiota of the poor-BGRI group. Furthermore, the differential bacteria showed extensive associations with clinical indices. ROC curves, separately plotted based on Romboutsia and Fusicatenibacter, achieved area under the curve values of 0.7193 and 0.6839, respectively. This study identified the efficient discriminative power of characteristic microbiota in BGRI patients with different outcomes and provided novel insights into the associations of gut microbiota with related risk factors.

Treatment of insomnia in myasthenia gravis-A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia.

Objectives: This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia. Methods: This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4-5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication. Results: A total of 75 MG patients with insomnia were included in this study. After 4-5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders. Conclusion: Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment.