Prognostic utility of preoperative platelet-to-albumin ratio in surgically treated oral cavity cancer patients.

BACKGROUND: This study aimed to explore the prognostic utility of the preoperative platelet-to-albumin ratio (PAR) among patients with oral cavity squamous cell carcinoma (OSCC). METHODS: We retrospectively reviewed of 355 patients with surgically-treated OSCC between 2008 and 2017. The optimal PAR cutoff for patient stratification was determined through X-tile analysis. Prognostic variables for disease-free survival (DFS) and overall survival (OS) were identified using Cox proportional hazards models. We developed a PAR-based nomogram to predict personalized OS. RESULTS: We determined the optimal PAR cutoff to be 7.45. A PAR of ≥7.45 was an independent negative prognostic factor for DFS and OS (hazard ratio = 1.748 and 2.386; p = 0.005 and p < 0.001, respectively). The developed nomogram demonstrates the practical utility of PAR and accurately predicts personalized OS. CONCLUSIONS: The preoperative PAR is a promising and cost-effective prognostic biomarker for patients with surgically-treated OSCC; the PAR-based nanogram accurately predicts OS for such patients.

Data-driven, two-stage machine learning algorithm-based prediction scheme for assessing 1-year and 3-year mortality risk in chronic hemodialysis patients.

Life expectancy is likely to be substantially reduced in patients undergoing chronic hemodialysis (CHD). However, machine learning (ML) may predict the risk factors of mortality in patients with CHD by analyzing the serum laboratory data from regular dialysis routine. This study aimed to establish the mortality prediction model of CHD patients by adopting two-stage ML algorithm-based prediction scheme, combined with importance of risk factors identified by different ML methods. This is a retrospective, observational cohort study. We included 800 patients undergoing CHD between December 2006 and December 2012 in Shin-Kong Wu Ho-Su Memorial Hospital. This study analyzed laboratory data including 44 indicators. We used five ML methods, namely, logistic regression (LGR), decision tree (DT), random forest (RF), gradient boosting (GB), and eXtreme gradient boosting (XGB), to develop a two-stage ML algorithm-based prediction scheme and evaluate the important factors that predict CHD mortality. LGR served as a bench method. Regarding the validation and testing datasets from 1- and 3-year mortality prediction model, the RF had better accuracy and area-under-curve results among the five different ML methods. The stepwise RF model, which incorporates the most important factors of CHD mortality risk based on the average rank from DT, RF, GB, and XGB, exhibited superior predictive performance compared to LGR in predicting mortality among CHD patients over both 1-year and 3-year periods. We had developed a two-stage ML algorithm-based prediction scheme by implementing the stepwise RF that demonstrated satisfactory performance in predicting mortality in patients with CHD over 1- and 3-year periods. The findings of this study can offer valuable information to nephrologists, enhancing patient-centered decision-making and increasing awareness about risky laboratory data, particularly for patients with a high short-term mortality risk.

A New Predictive Equation for Estimating Serum Ionized Calcium Levels in Patients on Chronic Hemodialysis.

BACKGROUND Circulating calcium mainly carries out its physiologic function in its ionized form (iCa). Clinically, iCa is usually estimated by multiplying the total calcium (TCa) level by 0.5 in the general population, but this method is not accurate when applied to patients on long-term hemodialysis (CHD). Accordingly, this study aimed to develop a predictive function for iCa in patients on CHD by incorporating TCa and other additional variables. MATERIAL AND METHODS This was a retrospective cross-sectional study consisting of 2 cross-sectional datasets: a derivation set including 469 CHD patients in June 2019, and a validation set including 446 CHD patients in September 2019. The derivation set's data were analyzed using the stepwise model selection of machine learning with 10-fold cross-validation to develop a predictive function for iCa. This predictive function was then applied to the validation set's data, and the predictive function's estimated iCa was compared with the actual laboratory iCa by using the paired-samples t test and intraclass correlation coefficient. RESULTS After analyzing the routine laboratory data parameters of patients in the derivation set, the following 5 variables were included in the predictive function of iCa: blood urea nitrogen, creatinine, phosphate, TCa, and albumin. This predictive function was applied to the validation set to yield an estimated iCa level that was not significantly different from the laboratory-measured iCa level of the validation dataset (P=0.676) with an excellent ICC of 0.905. CONCLUSIONS We developed a new predictive function that accurately measures the iCa in patients on CHD by using routine laboratory data.

An integrated machine learning predictive scheme for longitudinal laboratory data to evaluate the factors determining renal function changes in patients with different chronic kidney disease stages.

Background and objectives: Chronic kidney disease (CKD) is a global health concern. This study aims to identify key factors associated with renal function changes using the proposed machine learning and important variable selection (ML&IVS) scheme on longitudinal laboratory data. The goal is to predict changes in the estimated glomerular filtration rate (eGFR) in a cohort of patients with CKD stages 3-5. Design: A retrospective cohort study. Setting and participants: A total of 710 outpatients who presented with stable nondialysis-dependent CKD stages 3-5 at the Shin-Kong Wu Ho-Su Memorial Hospital Medical Center from 2016 to 2021. Methods: This study analyzed trimonthly laboratory data including 47 indicators. The proposed scheme used stochastic gradient boosting, multivariate adaptive regression splines, random forest, eXtreme gradient boosting, and light gradient boosting machine algorithms to evaluate the important factors for predicting the results of the fourth eGFR examination, especially in patients with CKD stage 3 and those with CKD stages 4-5, with or without diabetes mellitus (DM). Main outcome measurement: Subsequent eGFR level after three consecutive laboratory data assessments. Results: Our ML&IVS scheme demonstrated superior predictive capabilities and identified significant factors contributing to renal function changes in various CKD groups. The latest levels of eGFR, blood urea nitrogen (BUN), proteinuria, sodium, and systolic blood pressure as well as mean levels of eGFR, BUN, proteinuria, and triglyceride were the top 10 significantly important factors for predicting the subsequent eGFR level in patients with CKD stages 3-5. In individuals with DM, the latest levels of BUN and proteinuria, mean levels of phosphate and proteinuria, and variations in diastolic blood pressure levels emerged as important factors for predicting the decline of renal function. In individuals without DM, all phosphate patterns and latest albumin levels were found to be key factors in the advanced CKD group. Moreover, proteinuria was identified as an important factor in the CKD stage 3 group without DM and CKD stages 4-5 group with DM. Conclusion: The proposed scheme highlighted factors associated with renal function changes in different CKD conditions, offering valuable insights to physicians for raising awareness about renal function changes.

Association Between Fatty Liver Index, Controlled Attenuation Parameter, and Metabolic Syndrome Stages: A Community-Based Study.

BACKGROUND Controlled attenuation parameter (CAP) is a recent ultrasound-based method for measuring hepatic steatosis, which is common in patients with metabolic syndrome (MetS). The fatty liver index (FLI), an algorithm-based method, is frequently used to evaluate hepatic steatosis. This study assessed how FLI and CAP relate to the earlier MetS stage and their ability to identify it. MATERIAL AND METHODS A total of 170 community-based individuals were studied. Demographic information, body mass index, waist circumference, and blood pressures were collected. CAP was assessed by FibroScan. Fasting glucose, lipid tests, and γ-glutamyl transferase were measured. The CAP and FLI results were categorized into quartiles, with the MetS stages as the main outcomes. The odds ratio (OR) of the outcomes was calculated using logistic regression. The area under the curve in receiver operating characteristic analysis (AUC-ROC) was used to detect the stages of MetS. Sensitivity, specificity, and appropriate cut-offs based on ROC analysis are shown. RESULTS The higher the FLI or CAP category, the lower the proportion of non-MetS and the higher the proportion of moderate MetS. Each single-quartile increase in FLI and CAP was associated with an increased likelihood of being in the higher MetS stages - FLI: adjusted OR 3.1 (2.23-4.32); CAP: adjusted OR 1.96 (1.48-2.59). In the ROC analysis, FLI had a higher AUC-ROC than CAP in separating the stages of MetS, although findings were significant (P<0.001). FLI in detecting the stages of mild-to-severe versus non-MetS performed well (AUC-ROC [95% confidence interval]: 0.79 [0.72-0.87]), with high sensitivity (0.86) but low specificity (0.62). CONCLUSIONS FLI and CAP were positively associated with the MetS stage and its components, suggesting that they could be used as a MetS screening tool in community studies.

Prognostic utility of neutrophil-to-albumin ratio in surgically treated oral squamous cell carcinoma.

BACKGROUND: We aimed to evaluate the prognostic significance of preoperative neutrophil-to-albumin ratio (NAR) in oral squamous cell carcinoma (OSCC). METHODS: A total of 622 patients with surgically treated OSCC were enrolled. NAR was defined as the absolute neutrophil count divided by the serum albumin level in peripheral blood before the radical surgery. Cox proportional hazards model were used to discover survival outcome-associated factors. RESULTS: The optimal cut-off of NAR to predict overall survival (OS) was determined to be 0.1. In Cox model, high NAR was identified as an independent negative prognosticator of OS, cancer-specific survival, and recurrence-free survival (adjusted hazard ratio: 1.503, 1.958, and 1.727, respectively; all p < 0.05). The NAR-based nomogram accurately predicted OS (concordance index: 0.750). CONCLUSION: Our study suggests that preoperative NAR is a convenient and effective prognostic marker for OSCC and NAR-based nomogram can be a promising prognostic tool in clinical setting.

Impact of Pre-Transplant Parathyroidectomy on Graft Survival: A Comparative Study of Renal Transplant Patients (2005-2015).

BACKGROUND Hyperparathyroidism poses significant risks for patients prior to kidney transplantation. However, the outcomes of patients who undergo parathyroidectomy before renal transplantation compared to those without such a procedure remain uncertain. This real-world data study aimed to examine the clinical outcomes of both patient groups. MATERIAL AND METHODS Using the Taiwan National Health Insurance Research Database, we conducted a retrospective cohort study on patients who underwent renal transplantation between January 2005 and December 2015. The patients were divided into two groups: a case group (n=294) with parathyroidectomy and a control group (n=588) without the need for parathyroidectomy before kidney transplantation. The groups were matched based on age, sex, dialysis vintage, and baseline characteristics at a 1:2 ratio. Hazard ratios (HR) were estimated using the Cox regression model. The main outcomes assessed were graft failure, mortality, and major adverse cardiovascular events (MACE) recorded until December 2019. RESULTS During a mean follow-up period of 6 years, a significant difference was observed in graft failure (HR 1.40; 95% confidence interval 1.10-1.79, p=0.007) between the two groups. After further adjustment, graft failure remained significant (HR 1.52; 95% CI 1.07-2.15, p=0.019). Additionally, machine learning-based feature selection identified the importance of parathyroidectomy (ranked 9 out of 11) before kidney transplantation in predicting subsequent graft failure. CONCLUSIONS Our study demonstrates that severe hyperparathyroidism requiring parathyroidectomy before kidney transplantation may contribute to poor post-transplant graft outcomes compared to patients who do not require parathyroidectomy.

The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer.

PURPOSE: This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell carcinoma (LAOSCC). METHODS: Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction. RESULTS: There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI <97.8). In Cox models, low GNRI remained an independent negative prognosticator of OS (HR: 1.6; 95% CI: 1.124-2.277; p = 0.009) and CSS (HR: 1.907; 95% CI: 1.219-2.984; p = 0.005). The c-index of the proposed nomogram, incorporating assorted clinicopathological factors and GNRI, had a statistically significant increase compared with the predictive nomogram constructed by the TNM staging system alone (0.692 vs. 0.637, p < 0.001)." CONCLUSION: Preoperative GNRI is an independent prognostic factor of OS and CSS in patients with LAOSCC. A multivariate nomogram that includes GNRI may better help us to accurately estimate individual survival outcomes.

Prognostic Utility of Neck Lymph Node-to-Primary Tumor Standardized Uptake Value Ratio in Oral Cavity Cancer.

We investigated the prognostic utility of preoperative neck lymph node-to-primary tumor maximum standardized uptake value ratios (NTRs) in oral cavity squamous cell carcinoma (OSCC). We retrospectively reviewed the medical records of 141 consecutive patients who were diagnosed as having OSCC and had received fluorodeoxyglucose-positron emission tomography within 2 weeks prior to radical surgery between 2009 and 2018. To determine the optimal NTR cutoff, receiver operating characteristic analysis for overall survival (OS) was executed. The NTR's prognostic value for disease-free survival (DFS) and OS were determined through Cox proportional hazards analysis and the Kaplan-Meier method. We determined the median (range) follow-up duration to be 35.2 (2.1-122.4) months. The optimal NTR cutoff was 0.273, and patients with a higher NTR (≥0.273) exhibited significantly worse DFS and OS (p = 0.010 and 0.003, respectively). A higher NTR (≥0.273) predicted poorer DFS (hazard ratio: 2.696, p = 0.008) and OS (hazard ratio: 4.865, p = 0.003) in multivariable analysis. We created a nomogram on the basis of the NTR, and it could accurately predict OS (concordance index: 0.774). Preoperative NTRs may be a useful prognostic biomarker for DFS and OS in patients with OSCC who have undergone surgery. NTR-based nomograms may also be helpful prognostic tools in clinical trials.

The effects of using Tempeh as a supplement for type 2 diabetes.

Studies suggest that the consumption of Tempeh can improve abnormal blood glucose and lipid parameters, although it remains still unclear as to whether Tempeh can improve tissue damage. In our study, db/db obese diabetic mice were given Tempeh 1 (300 mg/kg) and Tempeh 2 (600 mg/kg) for 3 months. The tissue samples collected were stained using different tissue-staining methodologies and were compared with the diabetic control group that was not given any Tempeh. Our results demonstrated that consuming high-dose Tempeh for 1 month could significantly reduce serum glucose and body weight in mice whereas the tissue section of our result could validate that consuming high-dose Tempeh for 3 months effectively improves lipid droplet size and lipid accumulation in the liver, aorta, and kidney of the mice. Moreover, an indication of the recovery of the damaged tissue could be observed in the heart and pancreatic tissue when high dosage of Tempeh was given as a treatment. Thus, it can be concluded that continuous consumption of Tempeh as a treatment could improve both blood glucose and body weight of diabetic mice while also improving lipid accumulation and tissue damage.

Lymph node ratio as a survival predictor for head and neck squamous cell carcinoma with multiple adverse pathological features.

BACKGROUND: The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features. METHODS: In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled. RESULTS: The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016). CONCLUSION: For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.

A Nomogram Incorporating Neutrophil-to-Lymphocyte Ratio and Squamous Cell Carcinoma Antigen Predicts the Prognosis of Oral Cancers.

We introduced a novel squamous cell carcinoma inflammatory index (SCI) and explored its prognostic utility for individuals with operable oral cavity squamous cell carcinomas (OSCCs). We retrospectively analyzed data from 288 patients who were given a diagnosis of primary OSCC from January 2008 to December 2017. The SCI value was derived by multiplying the serum squamous cell carcinoma antigen and neutrophil-to-lymphocyte ratio values. We appraised the associations of the SCI with survival outcomes by performing Cox proportional hazards and Kaplan-Meier analyses. We constructed a nomogram for survival predictions by incorporating independent prognostic factors in a multivariable analysis. By executing a receiver operating characteristic curve analysis, we identified the SCI cutoff to be 3.45, and 188 and 100 patients had SCI values of <3.45 and ≥3.45, respectively. The patients with a high SCI (≥3.45) were associated with worse disease-free survival and overall survival than those with a low SCI (<3.45). An elevated preoperative SCI (≥3.45) predicted adverse overall survival (hazard ratio [HR] = 2.378; p < 0.002) and disease-free survival (HR = 2.219; p < 0.001). The SCI-based nomogram accurately predicted overall survival (concordance index: 0.779). Our findings indicate that SCI is a valuable biomarker that is highly associated with patient survival outcomes in OSCC.

High intact fibroblast growth factor 23 levels associated with low hemoglobin levels in patients on chronic hemodialysis.

Introduction: A negative association between C-terminal fibroblast growth factor 23 (cFGF23) and hemoglobin (Hb) levels has been reported in patients with predialysis chronic kidney disease. In dialysis patients, the dominant form of serum FGF23 is intact FGF23 (iFGF23); however, its association with the Hb level remains unclear. Therefore, simultaneously monitoring iFGF23 and cFGF23 levels is crucial. In this study, we investigated the associations between both forms of FGF23 (iFGF23 and cFGF23) and renal anemia in chronic hemodialysis (CHD) patients. Methods: We included 166 CHD patients from two hospitals in this cross-sectional, observational study. The primary predictors were serum iFGF23, cFGF23, and iFGF23/cFGF23 levels. The main outcome was the Hb level. Results: Among the CHD patients included, 60.8% were men with a mean age of 59.4 ± 12.7 years. In the crude analysis, iFGF23 and iFGF23/cFGF23 levels showed a significant negative association (-0.27, p = 0.004 and -0.22, p = 0.034, respectively) with the Hb level. Even after adjusting for multiple variables (a parsimonious model), every increment of natural log transformation by 1 for (ln)iFGF23 and ln(iFGF23/cFGF23) levels showed a negative correlation with the Hb level (estimate: -0.27 [95%CI: -0.44, -0.10, p = 0.001]; -0.19 [95%CI: -0.37, -0.01, p = 0.042], respectively), whereas both were positively associated with erythropoietin-stimulating agent (ESA) hyporesponsiveness (odds ratio [OR]: [95%CI: 2.30, 1.26-4.17], p = 0.006; 1.95 [95%CI: 1.08-3.50], p = 0.025). Moreover, these abovementioned associations were more dominant in patients with diabetes who used angiotensin receptor blockers. Discussion: In conclusion, a negative association between serum iFGF23 or iFGF23/cFGF23 level and the Hb level was observed in our CHD patients. Meanwhile, a higher iFGF23 or iFGF23/cFGF23 level may predispose patients to ESA hyporesponsiveness.

Oxidative stress involves phenotype modulation of morbid soreness symptoms in fibromyalgia.

OBJECTIVES: Muscle soreness occurs after exercise and also in musculoskeletal diseases, such as fibromyalgia (FM). However, the nosography and pathoetiology of morbid soreness in FM remain unknown. This study aimed to investigate the morbid soreness of FM, evaluate its therapeutic responses and probe its pathophysiology with metabolomics profiling. METHODS: Patients with newly diagnosed FM were prospectively recruited and completed self-report questionnaires pertaining to musculoskeletal symptoms. The phenotypes and metabotypes were assessed with variance, classification and correlation analyses. RESULTS: Fifty-one patients and 41 healthy controls were included. Soreness symptoms were prevalent in FM individuals (92.2%). In terms of manifestations and metabolomic features, phenotypes diverged between patients with mixed pain and soreness symptoms (FM-PS) and those with pain dominant symptoms. Conventional treatment for FM did not ameliorate soreness severity despite its efficacy on pain. Moreover, despite the salient therapeutic efficacy on pain relief in FM-PS cases, conventional treatment did not improve their general disease severity. Metabolomics analyses suggested oxidative metabolism dysregulation in FM, and high malondialdehyde level indicated excessive oxidative stress in FM individuals as compared with controls (p=0.009). Contrary to exercise-induced soreness, lactate levels were significantly lower in FM individuals than controls, especially in FM-PS. Moreover, FM-PS cases exclusively featured increased malondialdehyde level (p=0.008) and a correlative trend between malondialdehyde expression and soreness intensity (r=0.337, p=0.086). CONCLUSIONS: Morbid soreness symptoms were prevalent in FM, with the presentation and therapeutic responses different from FM pain conditions. Oxidative stress rather than lactate accumulation involved phenotype modulation of the morbid soreness in FM. TRIAL REGISTRATION NUMBER: NCT04832100.

Effect of omega-6 linoleic acid on neurobehavioral development in Caenorhabditis elegans.

Linoleic acid (LA, omega-6), an essential polyunsaturated fatty acid, is supplied by vegetable oils such as corn, sunflower and soybean. Supplementary LA in infants and children is required for normal growth and brain development, but has also been reported to induce brain inflammation and neurodegenerative diseases. This controversial role of LA development requires further investigation. Our study utilized Caenorhabditis elegans (C. elegans) as a model to clarify the role of LA in regulating neurobehavioral development. A mere supplementary quantity of LA in C. elegans larval stage affected the worm's locomotive ability, intracellular ROS accumulation and lifespan. We found that more serotonergic neurons were activated by supplementing LA above 10 µM thereby promoting locomotive ability with upregulation of serotonin-related genes. Supplementation with LA above 10 µM also inhibited the expression of mtl-1, mtl-2 and ctl-3 to accelerate oxidative stress and attenuate lifespan in nematodes; however, enhancement of stress-related genes such as sod-1, sod-3, mtl-1, mtl-2 and cyp-35A2 by supplementary LA under 1 µM decreased oxidative stress and increased the worm's lifespan. In conclusion, our study reveals that supplementary LA possesses both pros and cons in worm physiology and provides new suggestions for LA intake administration in childhood.

7,10,13,16-Docosatetraenoic acid impairs neurobehavioral development by increasing reactive oxidative species production in Caenorhabditis elegans.

AIMS: To investigate human breast milk (HBM) lipids that may adversely affect infant neurodevelopment. MAIN METHODS: We performed multivariate analyses that combined lipidomics and psychologic Bayley-III scales to identify which HBM lipids are involved in regulating infant neurodevelopment. We observed a significant moderate negative correlation between 7,10,13,16-docosatetraenoic acid (omega-6, C22H36O2, the common name adrenic acid, AdA) and adaptive behavioral development. We further studied the effects of AdA on neurodevelopment by using Caenorhabditis elegans (C. elegans) as a model. Worms from larval stages L1 to L4 were supplemented with AdA at 5 nominal concentrations (0 µM [control], 0.1 µM, 1 µM, 10 µM, and 100 µM) and subjected to behavioral and mechanistic analyses. KEY FINDINGS: Supplementation with AdA from larval stages L1 to L4 impaired neurobehavioral development, such as locomotive behaviors, foraging ability, chemotaxis behavior, and aggregation behavior. Furthermore, AdA upregulated the production of intracellular reactive oxygen species. AdA-induced oxidative stress blocked serotonin synthesis and serotoninergic neuron activity and inhibited expression of daf-16 and the daf-16-regulated genes mtl-1, mtl-2, sod-1, and sod-3, resulting in attenuation of the lifespan in C. elegans. SIGNIFICANCE: Our study reveals that AdA is a harmful HBM lipid that may have adverse effects on infant adaptive behavioral development. We believe this information may be critical for AdA administration guidance in children's health care.

TRPC7 facilitates cell growth and migration by regulating intracellular Ca2+ mobilization in lung adenocarcinoma cells.

Transient receptor potential canonical 7 (TRPC7) has been reported to mediate aging-associated tumorigenesis, but the role of TRPC7 in cancer malignancy is still unclear. TRPC7 is associated with tumor size in patients with lung adenocarcinoma and the present study further evaluated the underlying mechanism of TRPC7 in the regulation of cancer progression. The clinicopathological role of TRPC7 was assessed using immunohistochemistry staining and the pathological mechanism of TRPC7 in lung adenocarcinoma cells was determined using cell cycle examination, invasion and calcium response assays, and immunoblot analysis. The results indicated that high TRPC7 expression was associated with a lower 5-year survival rate compared with low TRPC7 expression, which suggested that TRPC7 expression was inversely associated with overall survival in patients with lung adenocarcinoma. TRPC7 serves a pathological role by facilitating the enhancement of cell growth and migration with increased phosphorylation of Ca2+/calmodulin-dependent protein kinase II, AKT and ERK. TRPC7 knockdown in lung adenocarcinoma cells restrained cell cycle progression and cell migration by interrupting the TRPC7-mediated Ca2+ signaling-dependent AKT and MAPK signaling pathways. These findings demonstrated for the first time a role of oncogenic TRPC7 in the regulation of cancer malignancy and could provide a novel therapeutic molecular target for patients with lung adenocarcinoma.

Serum Intact Fibroblast Growth Factor 23 Levels Are Negatively Associated with Bone Mineral Density in Chronic Hemodialysis Patients.

(1) Background: Fibroblast growth factor 23 (FGF23) is predominantly secreted from bone and plays an important role in mineral balance in chronic kidney disease. However, the relationship between FGF23 and bone mineral density (BMD) in chronic hemodialysis (CHD) patients remains unclear. (2) Methods: This was a cross-sectional observational study that involved 43 stable outpatients on CHD. A linear regression model was used to determine risk factors for BMD. Measurements included serum hemoglobin, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), sclerostin, Dickkopf-1, α-klotho, 1,25-hydroxyvitamin D, intact parathyroid hormone levels and dialysis profiles. (3) Results: Study participants had a mean age of 59.4 ± 12.3 years, and 65% were male. In the multivariable analysis, cFGF23 levels showed no significant associations with the BMD of the lumbar spine (p = 0.387) nor that of the femoral head (p = 0.430). However, iFGF23 levels showed a significant negative association with the BMD of the lumbar spine (p = 0.015) and that of the femoral neck (p = 0.037). (4) Conclusions: Among patients on CHD, higher serum iFGF23 levels, but not serum cFGF23 levels, were associated with lower BMD values of the lumbar spine and femoral neck. However, further research is required to validate our findings.

Systemic and Local Effects Among Patients With Betel Quid-Related Oral Cancer.

The major predisposing factors of developing oral cancer include smoking, alcohol drinking, and betel quid chewing. Betel quid chewing could cause the abrasion and damage of oral mucosa by crude fibers, chemical insults by additive slaked lime, and arecoline from areca nut. These would lead to the local consequence of oral submucosal fibrosis, which is regarded clinically as a precancer lesion and a major cause of trismus. In addition, the components and additives in betel quid contain chemical toxins and carcinogens, which would further affect the oral mucosa and gradually develop a malignancy. Following literature review, aside from having a greater total tumor burden and more local diseases in the oral cavity and digestive tract, patients with betel quid-related oral cancer also have more systemic diseases from metabolic syndrome, hypertension, cardiovascular disease, type II diabetes mellitus, and obesity than those without this habit. In conclusion, those patients who have the history of smoking, alcohol drinking, and betel quid chewing would present much more unique clinical characteristics than those who only have a history of smoking and alcohol drinking. More attention should therefore be paid to pretreatment evaluation, treatment strategy, and posttreatment follow-up among betel quid chewers.