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.

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.

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.

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.

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.

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.

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.

Unraveling the molecular crosstalk and immune landscape between COVID-19 infections and ischemic heart failure comorbidity: New insights into diagnostic biomarkers and therapeutic approaches.

BACKGROUND: Coronavirus disease 2019 (COVID-19), resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), remains a persistent global health concern. Evidence has highlighted a significant association between COVID-19 and ischemic heart failure (IHF), contributing to disease progression and increased mortality. This study identified diagnostic biomarkers for these comorbidities and elucidated disease progression's molecular mechanisms. METHODS: We retrieved differentially expressed gene (DEG) data for COVID-19 and IHF from publicly available microarray and RNA-Seq datasets to investigate the underlying mechanisms and potential pathways associated with the co-occurrence of COVID-19 and IHF. By intersecting the results from the two diseases, we obtained diagnostic biomarkers using SVM-RFE and LASSO algorithms. Animal experiments and immunological analyses were conducted to help understand the association between SARS-CoV-2 and IHF in patients, enabling early diagnosis of disease progression. Finally, we analyzed the regulatory network of critical genes and identified potential drug compounds that could target the genetic links identified in our study. RESULTS: 1974 common DEGs were identified between COVID-19 and IHF, contributing to disease progression and potential cancer risk by participating in immune and cancer-related pathways. In addition, we identified six hub genes (VDAC3, EIF2AK2, CHMP5, FTL, VPS4A, and CHMP4B) associated with the co-morbidity, and their diagnostic potential was confirmed through validation using relevant datasets and a mouse model. Functional enrichment analysis and examination of immune cell infiltration revealed immune dysregulation after disease progression. The comorbid hub genes exhibited outstanding immunomodulatory capacities. We also constructed regulatory networks tightly linked to both disorders, including transcription factors (TFs), miRNAs, and genes at both transcriptional and post-transcriptional levels. Finally, we identified 92 potential drug candidates to enhance the precision of anti-comorbidity treatment strategies. CONCLUSION: Our study reveals a shared pathogenesis between COVID-19 and IHF, demonstrating that their coexistence exacerbates disease severity. By identifying and consolidating hub genes as pivotal diagnostic biomarkers for COVID-19 and IHF comorbidity, we have made significant advancements in understanding the underlying mechanisms of these conditions. Moreover, our study highlights dysregulated immunity and increased cancer risk in the advanced stages of disease progression. These findings offer novel perspectives for diagnosing and treating IHF progression during SARS-CoV-2 infection.

Does inclusion of bioactive n-3 PUFAs in parenteral nutrition benefit postoperative patients undergoing liver surgery? A systematic review and meta-analysis of randomised control trials.

OBJECTIVES: This meta-analysis aims to evaluate the effect of n-3 polyunsaturated fatty acids (PUFAs) as a part of parenteral nutrition in patients undergoing liver surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, the Cochrane Central Register of Controlled Trials, Springer link, Web of Science, China National Knowledge Infrastructure and VIP Database. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) and evaluated the outcomes of liver function, inflammatory reaction, the influence of certain markers of the immune system, and specific clinical indexes for patients undergoing liver surgery and receiving parenteral nutrition with n-3 PUFAs. DATA EXTRACTION AND SYNTHESIS: The Cochrane Collaboration's tool was used to assess the risk of bias for each study. Findings were summarised in Grades of Recommendation, Assessment, Development and Evaluation evidence profiles and synthesised qualitatively. RESULTS: Eight RCTs, including 748 patients (trial: 374; control: 374), were included in the meta-analysis. Compared with patients in the control group, the patients in the n-3 PUFA group who underwent liver surgery had significantly lower aspartate aminotransferase (mean difference, MD -42.72 (95% CI -71.91 to -13.52); p=0.004), alanine aminotransferase (MD -38.90 (95% CI -65.44 to -12.37); p=0.004), white cell count (MD -0.93 (95% CI -1.60 to -0.26); p=0.007) and IL-6 (MD -11.37 (95% CI -14.62 to -8.13); p<0.00001) levels and a higher albumin level (MD 0.42 (95% CI 0.26 to 0.57); p<0.00001). They also had fewer infection complications (OR 0.44 (95% CI 0.28 to 0.68); p=0.0003) and a shorter duration of hospital stay (MD -2.17 (95% CI -3.04 to -1.3); p<0.00001) than the controls. However, there were no significant differences in terms of total bilirubin, TNF-α, IL-2, IgA, IgG, IgM and CD3, biliary leakage and mortality between the two groups. CONCLUSIONS: We found that n-3 PUFAs can benefit patients undergoing liver surgery by improving liver function and certain clinical indexes and decreasing related inflammation factors. However, there are limited RCTs on the application of n-3 PUFAs for patients undergoing liver surgery. Further evidence of the benefit of n-3 PUFAs in these patients warrants further exploration.

The state of female hepato-pancreato-biliary (HPB) surgeons in China: see us in operation theater with great prospects.

OBJECTIVE: This study aims to investigate the proportion and distribution of female HPB surgeons in China, describe their current status, and analyze the possible barriers and challenges in their careers. METHOD: Tertiary hospitals with the division of HPB in mainland China in 2021 were enrolled and surgeon demographic information was collected through the review of official websites and/or telephone interviews. RESULTS: The majority of female HPB surgeons (72.92%) were located in the first or second-tier cities in mainland China, with an increasing number of new female HPB surgeons entering the field annually, particularly after 2005 (from 27 to 52 per 5 years). Despite no significant difference in academic backgrounds, female HPB surgeons initiated their careers at an earlier age and took a longer time to obtain chief titles (P < 0.05). Interestingly, female HPB surgeons performed laparoscopic complex HPB cases at a similar rate (95.42%) to their male counterparts and were more likely to specialize in endoscopic surgery (P = 0.021), with a similar ratio of obtaining administrative positions. CONCLUSION: Minimally invasive surgery may provide females with unprecedented opportunities in the HPB surgery field. However, despite the increasing numbers of female HPB surgeons, the proportion remains low in China.

Customed 3D-printed Polyetheretherketone (PEEK) Implant for Secondary Salvage Reconstruction of Mandibular Defects: Case Report and Literature Review.

Given the insufficient height of single-barrel fibula and inadequate bone volume of double-barrel vascularized fibula in mandibular reconstruction, it is a better choice to combine the upper full-thickness vascularized fibula with the lower half-thickness nonvascularized fibula. However, the nonvascularized fibula may fail due to complications, affecting the facial shape and occlusal function. Polyetheretherketone is a thermoplastic polymer used for bone defect reconstruction due to its good mechanical properties and biocompatibility. This case report mainly presents a secondary salvage reconstruction of the mandible by using customed 3-dimensional-printing polyetheretherketone, which restored the continuity and symmetry of the mandible, improved the patient's facial shape, and restored functional occlusion through dental implants. After a 28-month follow-up, no complications occurred, and the patient was satisfied with the final restoration.

Co-exposure of organophosphorus pesticides is associated with increased risk of type 2 diabetes mellitus in a Chinese population.

OBJECTIVE: The epidemiological evidence of human exposure to organophosphorus pesticides (OPPs) with type 2 diabetes mellitus (T2DM) and prediabetes (PDM) is scarce. We aimed to examine the association of T2DM/PDM risk with single OPP exposure and multi-OPP co-exposure. METHODS: Plasma levels of ten OPPs were measured using the gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) among 2734 subjects from the Henan Rural Cohort Study. We used generalized linear regression to estimate odds ratios (ORs) or ß with 95% confidence intervals (CIs), and constructed quantile g-computation and Bayesian kernel machine regression (BKMR) models to investigate the association of OPPs mixture with the risk of T2DM and PDM. RESULTS: High detection rates ranged from 76.35% (isazophos) to 99.17% (malathion and methidathion) for all OPPs. Several plasma OPPs concentrations were in positive correlation with T2DM and PDM. Additionally, positive associations of several OPPs with fasting plasma glucose (FPG) values and glycosylated hemoglobin (HbA1c) levels were observed. In the quantile g-computation, we identified significantly positive associations between OPPs mixtures and T2DM as well as PDM, and fenthion had the greatest contribution for T2DM, followed by fenitrothion and cadusafos. As for PDM, the increased risk was largely explained by cadusafos, fenthion, and malathion. Furthermore, BKMR models suggested that co-exposure to OPPs was linked to an increased risk of T2DM and PDM. CONCLUSION: Our findings suggested that the individual and mixture of OPPs exposure were associated with an increased risk of T2DM and PDM, implying that OPPs might act an important role in the development of T2DM.

Serum Progesterone is Negatively Associated with Hypertension and Blood Pressure Indicators Among Men and Postmenopausal Women.

Sex hormones have been shown to be negatively associated with hypertension, but the relationship between serum progesterone levels and hypertension has not been adequately studied. Therefore, we aimed to evaluate the association between progesterone and hypertension among Chinese rural adults. A total of 6222 participants were recruited, which included 2577 men and 3645 women. The concentration of serum progesterone was detected by liquid chromatography-mass spectrometer system (LC-MS/MS). Logistic regression and linear regression were used to assess the associations between progesterone levels and hypertension and blood pressure related indicators, respectively. Constrained splines were used to fit the dose-response relationships of progesterone with hypertension and blood pressure related indicators. Moreover, the interactive effects of several lifestyle factors and progesterone were identified by a generalized linear model. After fully adjusting the variables, progesterone levels were inversely associated with hypertension in men [odds ratio (OR): 0.851, 95% confidence interval (CI): 0.752, 0.964]. Among men, a 2.738 ng/ml increase in progesterone was associated with a 0.557 mmHg decrease in diastolic blood pressure (DBP) (95% CI: -1.007, -0.107) and a 0.541 mmHg decrease in mean arterial pressure (MAP) (95% CI: -1.049, -0.034), respectively. Similar results were observed in postmenopausal women. Interactive effect analysis showed that only a significant interaction was observed between progesterone and educational attainment on hypertension in premenopausal women (p=0.024). Elevated levels of serum progesterone were associated with hypertension in men. Except for premenopausal women, a negative association of progesterone with blood pressure related indicators was observed.

Iron metabolism in non-anemic myasthenia gravis patients: A cohort study.

BACKGROUND: The association of iron metabolism parameters with disease severity and outcome in myasthenia gravis (MG) patients has not been reported. This study was conducted to determined clinical factors including iron metabolism parameters correlated with disease severity and future outcome in non-anemic immunotherapy-naïve MG patients first receiving immunotherapy. MATERIAL AND METHODS: One hundred and ten patients were included at baseline to explore predictor variables associated with disease severity represented by variables derived from MG activities of daily living (MG-ADL) score using multivariate logistic regression, after which 103 and 98 patients were included respectively in multivariate survival analyses at 6-month and 12-month follow-up to identify predictors for minimal manifestation status (MMS) after starting immunotherapy. RESULTS: Higher ferritin level was independently associated with higher risk of severe generalized disease in non-anemic immunotherapy-naïve MG patients. Total iron binding capacity <250 µg/dL and the interval between onset and immunotherapy <1 year were independent predictors for MMS at 6-month and 12-month follow-up after initiating immunotherapy. Transferrin <2.00 g/L was an independent predictor for MMS at 12-month follow-up. CONCLUSION: Iron metabolism parameters might be promising biomarkers for evaluating disease severity and guiding therapeutic decision in MG patients.

Iron metabolism patterns in non-anemic patients with myasthenia gravis: A cross-sectional and follow-up study.

Background and purpose: Iron metabolism in myasthenia gravis (MG) and factors associated with it are explored by few published studies. Therefore, this study aimed to compare iron metabolism patterns between patients with MG and healthy individuals as well as between the same group of patients before and after immunotherapy, and to identify predictors of iron metabolism disorders in MG. Materials and methods: For this study, 105 patients and healthy individuals were included at baseline, after which paired parametric and non-parametric tests were adopted to compare their iron metabolism patterns, and multivariate binary logistic regression was used to identify predictors of iron metabolism disorders. Patients with MG were then followed up for 12 ± 3 months to explore alterations in their iron metabolism patterns after starting immunotherapy with the help of paired tests. Results: Non-anemic immunotherapy-naive patients with MG had significantly lower serum iron (SI) and transferrin saturation (TS) levels than healthy individuals. Premenopausal female was significantly associated with SI < 65 µg/dL and iron deficiency in these patients. However, iron metabolism parameters did not significantly alter after around 12 months of immunotherapy in patients with MG. Conclusion: Iron inadequacy was present in patients with MG, particularly premenopausal female patients, and it would hardly improve after immunotherapy. Given the significant role of iron in human body, it should be given more attention in patients with MG.

FOXC2 as a prognostic marker and a potential molecular target in patients with human solid tumors.

Background: Forkhead Box Protein C2 (FOXC2) belongs to the Forkhead/Wing-helix family. The regulatory role of this transcription factor in physiological function and carcinogenic activity has been proven in subsequent investigations. However, there is still scarcity of evidence on the relationship between FOXC2 expression and prognosis in human solid tumors. We conducted this meta-analysis to evaluate the role of FOXC2 as a prognosis factor and a possible target marker in human solid tumors. Methods: PubMed, Web of Science, Embase, and the Cochrane library database were all searched methodically. Eligible publications on FOXC2 in human solid tumors were gathered and reviewed. The effect sizes were calculated using pooled hazard ratios (HRs) or odds ratios (ORs) with the corresponding 95% confidence interval (CI). Statistical analysis was conducted with Stata SE12.0. Results: This meta-analysis comprised 3,267 patients from 20 studies covering a variety of solid tumors. Increased FOXC2 expression was related to shorter overall survival (OS) (HR = 2.05, 95% CI: 1.73-2.42). High expression of FOXC2 is associated with lymph node metastases (OR = 3.33, 95% CI: 2.65-4.19), TNM stage (OR = 3.09, 95% CI: 2.00-4.78), and age (OR = 1.26, 95% CI: 1.06-1.50), according to the pooled ORs. However, no significant association was observed between the high expression of FOXC2 and sex, tumor size or tumor differentiation. Conclusion: Increased expression of FOXC2 is associated with unfavored OS, lymph node metastases, TNM stage, and age. FOXC2 is a promising prognostic marker and a novel target marker in human solid tumors.

Successful Management of Generalized Myasthenia Gravis Induced by Atezolizumab in a Patient With Extensive-Stage SCLC: A Case Report.

Immune checkpoint inhibitors including atezolizumab and durvalumab have been approved as the first-line treatment in extensive-stage SCLC. However, immune checkpoint inhibitors can cause immune-related adverse events, which will lead to the shelving of follow-up treatment and the progression and deterioration of SCLC. Myasthenia gravis (MG) is a relatively rare and fatal presentation of immune-related adverse events, and experience with immune-related MG in patients with SCLC is limited. Herein we present a patient who developed generalized MG after receiving three cycles of treatment with etoposide, carboplatin, and atezolizumab. Immune-related MG was identified, with pyridostigmine bromide, intravenous immunoglobulin, and glucocorticoids given in time. Fortunately, the patient's MG was relieved, and treatment of SCLC was restarted subsequently.

Application of Patient-Specific PEEK Implant for Aesthetic Considerations in Paranasal Augmentation.

The paranasal area is closely associated with midfacial esthetics. However, there is no special technique available to achieve ideal esthetics paranasal restoration. The present study aims to apply the 3D printed PolyEtherEtherKetone (PEEK) implants as an innovative solution for esthetic paranasal reconstruction. On the basis of the CT scan, the patient-specific PEEK implant and a surgical guiding plate were manufactured aided by a computer. Preoperative and postoperative CBCT data were utilized to evaluate esthetic outcomes. The average follow-up period was 13 months. All patients' wounds healed by first intention. The statistical analysis of preoperative and postoperative esthetic indices revealed light levels of postoperative paranasal depression ( P <0.001) and the wrinkle severity rating scale for nasolabial folds ( P <0.001). Moreover, the nasolabial angle increased ( P <0.05). The established 3D-printing PEEK implanted prosthesis can individually correct the depressed deformity of the paranasal region, and achieve favorable clinical esthetic outcomes.

Genetic Cross-Talk between Oral Squamous Cell Carcinoma and Type 2 Diabetes: The Potential Role of Immunity.

Background: This bioinformatics study was aimed at evaluating type 2 diabetes (T2D) and oral squamous cell carcinoma (OSCC) with regard to related immune cells and prognosis. Methods: We downloaded the data on OSCC from TCGA and for T2D from GEO database. Differentially expressed genes were analyzed, i.e., for OSCC genes with p value < 0.01, |log2(FC)| > 0; and for T2D, genes with p value < 0.05, |log2(FC)| > 0. The intersected genes between OSCC and T2D were cross-talk genes. The expression values of immune-related genes in case samples in OSCC and T2D were assessed and underwent multivariate and univariate analysis (Cox-PH model). The intersection between the immune genes and cross-talk genes was taken and further analyzed by recursive feature elimination (RFE), survival analysis, and ROC analysis. Results: 1008 cross-talk genes were acquired, including 28 common upregulated, 440 common downregulated, and 540 differently regulated DEGs. We extracted the gene expression value of 782 immune-related genes, of which seven increased immune cells were obtained. From the results, plasmacytoid dendritic cells and effector memory CD8 T cells were highly negatively correlated in both OSCC and T2D. After estimating a low- and high-risk model for survival, we found that activated dendritic cell was significantly different between high and low groups (p = 0.0095), followed by plasmacytoid dendritic cell. We integrated DE_Immune genes set 1 and DE_Immune genes set 2 and eight key immune-related cross-talk genes (C1QC, ABCD1, NOS2, PDIA4, IL1RN, ALOX15, CSE1L, and PSMC4) were evaluated. After ROC analysis, we obtained that ABCD1, C1QC, CSE1L, and PSMC4 had higher classification and prediction effects on OSCC and T2D. Conclusion: This study revealed a close relationship between T2D and OSCC. Thereby, plasmacytoid dendritic cell and activated dendritic cell-related genes were associated with the survival of T2D-related OSCC, while ABCD1, C1QC, CSE1L, and PSMC4 were the most important immune-related cross-talk genes.