Time-varying association of second primary malignancy and long-term survival outcomes in patients with head and neck cancer.

A high risk of developing second primary malignancy (SPM) has been reported among head and neck cancer patients. Here, we aimed to statistically quantify the impact of SPM development on the survival of head and neck cancer patients. Our study was conducted using the Surveillance, Epidemiology and End Results database to collect the data of 48 316 patients who received curative surgical resection for initial primary head and neck squamous cell carcinoma (IP-HNSCC) in 1975 to 2019. SPM diagnosis was treated as a time-varying covariate and multivariable Cox regression analysis was conducted to estimate the association between SPM development and survival, overall or by the subsite of IP-HNSCC. Of the included patients, 11 238 patients (23.3%) developed SPM during the follow-up period. A significant reduction in survival was observed among patients with SPM (hazard ratio [HR] for overall survival, 3.30; 95% confidence interval [CI]: 3.20-3.41). The impact of SPM development on reduced survival was more significant in patients with localized IP-HNSCC vs regional IP-HNSCC (HROS , 3.41; 95% CI: 3.24-3.6 vs HROS , 3.18; 95% CI: 3.05-3.31; P for interaction <.001). The survival impact of SPM development was more evident in younger patients than in older patients. SPM in lung and bronchus was associated with the most pronounced reduction in survival, overall and across all subsites of HNSCC. Our results indicated that SPM development led to a significant reduction in survival. A greater survival benefit may be achieved through intensive surveillance for SPM in lung and bronchus targeting younger patients and those with localized HNSCC.

Fusobacterium nucleatum impairs DNA mismatch repair and stability in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Dysbiosis of the laryngeal microbiota has been demonstrated to the development of head and neck squamous cell carcinoma (HNSCC), but the association of Fusobacterium and Fusobacterium nucleatum (F. nucleatum) with DNA mismatch repair (MMR) and microsatellite instability (MSI) has not been investigated. METHODS: The abundance of Fusobacterium and F. nucleatum, the status of deficient MMR (dMMR) and MSI, and MMR-related gene expression were analyzed in 171 HNSCC tissues, 61 paired para-tumor tissues, and 60 vocal cord polyp tissues. The molecular mechanism of F. nucleatum and MMR-related gene expression were investigated in two human HNSCC cell lines (Tu 686 and FD-LSC-1). RESULTS: Our results demonstrated that a high Fusobacterium abundance was detected in the HNSCC tissues and was exaggerated in the recurrent patients. We further found that a high Fusobacterium abundance was detected in the HNSCC tissues with dMMR and MSI. The Fusobacterium abundance was negatively correlated with the expression of MLH1, MSH2, and MSH6 in the HNSCC tissues. The Fusobacterium abundance was closely associated with the F. nucleatum abundance in the HNSCC tissues. F. nucleatum increased miR-205-5p expression to suppress MLH1, MSH2, and MSH6 expression via the TLR4- and MYD88-dependent innate immune signaling pathway, resulting in dMMR, DNA damage, and cell proliferation in HNSCC. CONCLUSIONS: F. nucleatum impacts HNSCC epigenetic changes in tissues with dMMR to promote DNA damage and cell proliferation by suppressing MMR-related gene expression via the TLR4/MYD88/miR-205-5p signaling pathway, which is valuable in the development of efficient strategies for HNSCC prevention and treatment. LAY SUMMARY: This study clearly indicates that Fusobacterium induced head and neck squamous cell carcinoma (HNSCC) aggressiveness to affect poor prognosis in HNSCC patients by epigenetic alteration of DNA mismatch repair (MMR) and microsatellite instability. Moreover, the research has shown that Fusobacterium nucleatum ( F. nucleatum ) impacts HNSCC epigenetic changes in tissues with deficient MMR to promote DNA damage and cell proliferation by suppressing MMRrelated gene expression via the TLR4/MYD88/miR-205-5p signaling pathway.

Oncologic outcomes of transoral laser microsurgery versus open partial laryngectomies in the management of early stage glottic carcinoma.

BACKGROUND: The oncologic outcomes between transoral laser microsurgery (TLM) and open partial laryngectomy (OPL) using comprehensive analysis in one clinical center is rare. The purpose of this study was to evaluate the oncologic outcomes of TLM in patients with early stage glottic carcinoma, and to compare the results with OPL. SUBJECTS AND METHODS: Records of 425 glottic carcinoma patients with T1 - T2 stage treated with TLM, vertical partial laryngectomy (VPL), and cricohyoidoepiglottopexy (CHEP) from 2005 to 2010 were retrospectively analyzed. The overall survival (OS), disease-specific survival (DSS), and laryngeal function preservation (LFP) of these three treatments were assessed. RESULTS: One hundred and twenty-two patients were treated with TLM. Regarding OPL, 167 patients underwent VPL, and 136 patients underwent CHEP. The mean age was 59.7 years, with men accounting for 97.2 % of all cases. The OS, DSS, and LFP rates of patients with anterior commissure (AC) involvement undergoing TLM were worse than those of patients without AC involvement, but these differences were not statistically significant. The 5-year OS, DSS, and LFP of patients undergoing TLM were 88.4 %, 89.9 %, and 83.5 %, respectively, and the oncologic outcomes of patients undergoing TLM, VPL, and CHEP were not statistically different. CONCLUSION: Glottic carcinoma patients with early stage treated with TLM experience satisfactory oncologic outcomes. No compelling difference in oncologic outcomes among three treatments of TLM, VPL and CHEP, as well as VPL and CHEP can be alternatives to patients who are not suitable for receiving TLM.

Effect of pre-discharge cardiopulmonary fitness on outcomes in patients with ST-elevation myocardial infarction after percutaneous coronary intervention.

BACKGROUND: The purpose of this study was to analyze cardiopulmonary fitness in Phase I cardiac rehabilitation on the prognosis of patients with ST-Elevation Myocardial Infarction (STEMI) after percutaneous coronary intervention (PCI). METHODS: The study enrolled a total of 499 STEMI patients treated with PCI between January 2015 and December 2015. Patients were assigned to individualized exercise prescriptions (IEP) group and non-individualized exercise prescriptions (NIEP) group according to whether they accept or refuse individualized exercise prescriptions. We compared the incidence of major cardiovascular events between the two groups. IEP group were further divided into two subgroups based on prognosis status, namely good prognosis (GP) group and poor prognosis (PP) group. Key cardio-pulmonary exercise testing (CPX) variables that may affect the prognosis of patients were identified through comparison of the cardio-respiratory fitness (CRF). RESULTS: There is no significant difference in the incidence of cardio-genetic death, re-hospitalization, heart failure, stroke, or atrial fibrillation between the IEP and the NIEP group. But the incidence of total major adverse cardiac events (MACE) was significantly lower in the IEP group than in the NIEP group (P = 0.039). The oxygen consumption (VO2) at ventilation threshold (VT), minute CO2 ventilation (E-VCO2), margin of minute ventilation carbon dioxide production (△CO2), rest partial pressure of end-tidal carbon dioxide(R-PETCO2), exercise partial pressure of end-tidal carbon dioxide(E-PETCO2) and margin of partial pressure of end-tidal carbon dioxide(△PETCO2) were significantly higher in the GP subgroup than in the PP subgroup; and the slope for minute ventilation/carbon dioxide production (VE/VCO2) was significantly lower in GP subgroup than in PP subgroup (P = 0.010). The VO2 at VT, VE/VCO2 slope, E-VCO2, △CO2, R-PETCO2, E-PETCO2 and margin of partial pressure of end-tidal carbon dioxide CO2 (△PETCO2) were predictive of adverse events. The VO2 at VT was an independent risk factor for cardiovascular disease prognosis. CONCLUSIONS: Individualized exercise prescription of Phase I cardiac rehabilitation reduced the incidence of cardiovascular events in patients with STEMI after PCI. VO2 at VT is an independent risk factor for cardiovascular disease prognosis, and could be used as an important evaluating indicator for Phase I cardiac rehabilitation.

Microbiota in the Throat and Risk Factors for Laryngeal Carcinoma.

The compositions and abundances of the microbiota in the ecological niche of the human throat and the possible relationship between the microbiota and laryngeal cancer are poorly understood. To obtain insight into this, we enrolled 27 laryngeal carcinoma patients and 28 subjects with vocal cord polyps as controls. For each subject, we simultaneously collected swab samples from the upper throat near the epiglottis (site I) and tissue samples from the vestibulum laryngis to the subglottic region (site II). The microbiota of the throat were fully characterized by pyrosequencing of barcoded 16S rRNA genes. We found 14 phyla, 20 classes, 38 orders, 85 families, and 218 genera in the throats of enrolled subjects. The main phyla were Firmicutes (54.7%), Fusobacteria (14.8%), Bacteroidetes (12.7%), and Proteobacteria (10.6%). Streptococcus (37.3%), Fusobacterium (11.3%), and Prevotella (10.6%) were identified as the three most predominant genera in the throat. The relative abundances of 23 bacterial genera in site I were significantly different from those in site II (P < 0.05). The relative proportions of 12 genera largely varied between laryngeal cancer patients and control subjects (P < 0.05). Collectively, this study outlined the spatial structure of microbial communities in the human throat. The spatial structure of bacterial communities significantly varied in two anatomical sites of the throat. The bacterial profiles of the throat of laryngeal cancer patients were strongly different from those of control subjects, and several of these microorganisms may be related to laryngeal carcinoma.

Notch1 overexpression associates with poor prognosis in human laryngeal squamous cell carcinoma.

OBJECTIVE: This study aimed to investigate the expression of Notch1 in human laryngeal squamous cell carcinoma (LSCC) tissues and its relationship to clinicopathologic characteristics as well as their prognostic value in LSCC. METHODS: Samples from 106 patients with LSCC were analyzed for Notch1 expression by immunohistochemical staining. The relationship between Notch1 expression and clinicopathologic parameters was subsequently analyzed. Univariate analysis and multivariate analysis of patient survival were examined using the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS: We found that Notch1 had positive expression in 71 of 106 cases of LSCC (66.98%), which was obviously higher than laryngeal normal tissues (P < .01) and significantly correlated with the clinical stage, lymph node metastasis, and histological grade (all Ps < .05). Univariate analysis revealed that Notch1 expression tended to show an unfavorable influence on overall survival (OS) and disease-free survival (DFS) (both Ps < .01). Multivariate analysis demonstrated that Notch1 was an independent prognostic factor for patients with LSCC (P < .05). CONCLUSION: These results reveal that Notch1 expression is a potential prognostic factor for malignant progression, metastasis, and survival of LSCC patients. Furthermore, it has been demonstrated that high expression of Notch1 was associated with unfavorable OS and DFS in LSCC patients.

Effects of exercise training on nitric oxide synthase in the kidney of spontaneously hypertensive rats.

Exercise training is known to have antihypertensive effects in humans and animals with hypertension, as well as to exhibit renal protective effects in animal models of hypertension and chronic renal failure. However, the mechanisms regulating these effects of exercise training remain unclear. The present study examined the effects of exercise training on nitric oxide synthase (NOS) in the kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Male SHR and WKY rats were randomly divided into a sedentary group and a treadmill exercise group for 8 weeks. Systolic blood pressure (SBP) was measured every 2 weeks by the tail-cuff method and urine and blood samples were collected after the exercise protocol. Nitric oxide synthase activity and protein expression and endothelial (e) NOS phosphorylation in the kidney were examined. Exercise training significantly lowered SBP, decreased urinary albumin excretion, thiobarbituric acid-reactive substances levels and renal NADPH oxidase activity, and increased creatinine clearance in SHR. Exercise training significantly increased plasma and urinary nitrate/nitrite, NOS activity and eNOS and neuronal NOS expression, but decreased eNOS phosphorylation at Ser(1177) and Thr(495) in kidneys of SHR and WKY rats. Renal NOS may be involved in the antihypertensive and renal protective effects of exercise training in SHR.

Exercise training upregulates nitric oxide synthases in the kidney of rats with chronic heart failure.

There is an interaction between heart and kidney diseases, which is a condition termed cardiorenal syndrome. Exercise training has cardioprotective effects, involving upregulation of endothelial (e) nitric oxide synthase (NOS) in the cardiovascular system. However, the effects of exercise training on NOS in the kidney with heart disease are unknown. The aim of the present study was to investigate whether exercise training upregulates NOS in the kidney, left ventricle and aorta of rats with chronic heart failure (CHF). Male Sprague-Dawley rats underwent left coronary artery ligation (LCAL) to induce CHF and were randomly assigned to sedentary or treadmill exercise groups 4 weeks after LCAL. Three days after exercising for 4 weeks, urine samples were collected for 24 h and blood samples were collected following decapitation. Nitric oxide synthase activity and protein expression were examined. Significant interactions between CHF and exercise training were observed on parameters of cardiac and renal function. Exercise training improved cardiac function, decreased plasma B-type natriuretic peptide levels, decreased urinary albumin excretion and increased creatinine clearance in CHF rats. Nitric oxide synthase activity, eNOS expression and neuronal (n) NOS expression were significantly decreased in the left ventricle and kidney of CHF rats. Exercise training significantly increased NOS activity and eNOS and nNOS expression. Upregulation of NOS in the kidney and left ventricle may contribute, in part, to the renal and cardiac protective effects of exercise training in cardiorenal syndrome in CHF rats.

Effect of temperature fluctuations in cold seasons on acute myocardial infarction hospitalisations in northeast China: a retrospective observational cohort study.

OBJECTIVE: This study aimed to determine the potential influence of ambient temperature on the incidence of acute myocardial infarction (AMI). DESIGN: A retrospective observational cohort study. SETTING: Changchun, a northeastern city in China, has a temperate continental humid climate. PARTICIPANTS: 1933 AMI patients admitted to the outpatient department of the First Hospital of Jilin University were included in the study from 1 January 2017 to 31 December 2019. OUTCOME MEASURE: We explored the effect of daily minimum and maximum temperatures, as well as temperature changes on two adjacent days, on the incidence of daily AMI from 1 to 5 days later in Changchun. RESULTS: We found that the average daily number of AMI cases was higher from October to April in cold season compared with the period between May and September in warm season. When the daily maximum temperature is ≤-6°C on the -2nd day, the incidence of AMI>3 persons more than doubled (from 8.51% and 10.88% to 20.23%) in the next 2 days (p=0.027); and more than 65% of the days had a maximum temperature fluctuation on |(-2nd day) - (-3rd day)| ≥2°C in these days, the OR of the daily incidence of AMI>3 persons is 3.107 (p=0.018); and in these days with enhanced temperature fluctuations, the proportion of AMI patients with hypertension had increased significantly from 20.83% to 45.39% (p=0.023). CONCLUSION: Ambient temperature as environmental factor has a seasonal effect on the incidence of AMI in temperate continental humid climate regions, with a 2-3 days lag. Furthermore, the key factor contributing to the increase in the daily incidence of AMI during the cold season is temperature fluctuations, and maintaining a constant temperature may aid in preventing the occurrence of AMI. TRIAL REGISTRATION NUMBER: ChiCTR2300068294.

Trends in the surgical management of parapharyngeal space tumors: A single-center retrospective analysis.

PURPOSE: Surgery remains the mainstay treatment for parapharyngeal space (PPS) tumors. Given the rapid advance and increasing usage of endoscopic and robotic techniques, we aimed to investigate the surgical trends of PPS tumors in our institution and analyze their impact on patients' treatment outcomes. MATERIALS AND METHODS: All patients who underwent surgical resection of PPS tumors from 2014 to 2021 at the Eye, Ear, Nose, and Throat Hospital of Fudan University were retrospectively reviewed. Student's t-test, Chi-square test, and multinomial logistic regression analyses were used to compare the surgical outcomes between groups. RESULT: Of the included 389 patients, the recipients of endoscopic surgery have largely increased in our center, with 17 of 134 cases (12.7%) in the group 2014-2017 and 187 of 255 cases (73.3%) in the group 2018-2021. The use of transoral and trans-nasal approaches increased in recent years (5.2% in 2014-2017 vs. 26.0% in 2018-2021), while that of trans-mandibular and lateral skull base approaches decreased (5.9% in 2014-2017 vs. 0.8% in 2018-2021). Decreased blood loss of operation and decreased risks of postoperative neurovascular complications were observed in the group 2018-2021. Similar findings were observed among patients receiving endoscopic surgery when compared with those receiving conventional surgery. CONCLUSION: In our institution, the overall trends in the surgical management of PPS tumors moved towards minimally invasive approaches with the assistance of endoscopy or surgical robots. The two surgical techniques were feasible and safe, and to a great extent, contributed to the improved surgical outcomes we observed in recent years.

Disorder of fatty acid metabolism in the kidney of PAN-induced nephrotic rats.

Proteinuria is considered to play an essential role in the progression of tubulointerstitial damage, which causes end-stage renal disease. Fatty acid-binding albumins are filtered through glomeruli and reabsorbed into proximal tubular epithelial cells (PTECs). However, the role of fatty acid metabolism associated with albuminuria in the development of tubulointerstitial damage remains unclear. Thus, the present study was designed to determine the changes of fatty acid metabolism in the nephrotic kidney. To induce nephrotic syndrome, Sprague-Dawley rats (SDRs) and Nagase analbuminemic rats (NARs) with inherited hypoalbuminemia were treated with a single injection of puromycin aminonucleoside (PAN). In SDRs, PAN treatment induced massive proteinuria and albuminuria and caused tubular damage, apoptosis, and lipid accumulation in PTECs. Among the enzymes of fatty acid metabolism, expressions of medium-chain acyl-CoA dehydrogenase (MCAD) and cytochrome P-450 (CYP)4A significantly decreased in PTECs of PAN-treated SDRs. Expressions of peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α and estrogen-related receptor (ERR)α also significantly decreased, without changes in the expression of PPAR-α. In NARs, PAN treatment induced proteinuria but not albuminuria and did not cause tubular damage, apoptosis, or lipid accumulation. Expressions of MCAD, PGC-1α, or ERRα did not change in the kidney cortex of PAN-treated NARs, but the expression of CYP4A significantly decreased. These results indicate that massive albuminuria causes tubular damage and lipid accumulation with the reduction of MCAD, CYP4A, PGC-1α, and ERRα in PTECs.

Lateral Involvement in Different Sized Papillary Thyroid Carcinomas Patients with Central Lymph Node Metastasis: A Multi-Center Analysis.

Objective: To quantitatively predict the probability of lateral lymph node metastasis (LLNM) for papillary thyroid carcinomas (PTC) patients with central lymph node metastasis (CLNM) in order to guide postoperative adjuvant treatment. Methods: Five hundred and three PTC patients with CLNM from three medical centers were retrospectively analyzed. Results: The LLNM rate for all patients was 23.9% (120 in 503), with 15.5% (45 in 291) and 35.4% (75 in 212) for patients with papillary thyroid microcarcinoma (PTMC) and large papillary thyroid carcinoma (LPTC), respectively. Patients with no fewer than five positive central lymph nodes (CLN) exhibited a higher risk of LLNM. For patients with fewer than five positive CLN, a maximum diameter of positive CLN > 0.5 cm and the presence of ipsilateral nodular goiter were identified as independent risk factors of LLNM for papillary thyroid microcarcinoma (PTMC) patients. The independent risk factors of LLNM for large papillary thyroid carcinoma (LPTC) patients included a tumor located in the upper portion of thyroid, maximum tumor diameter ≥ 2.0 cm, maximum diameter of positive CLN > 0.5 cm, and the presence of thyroid capsular invasion. Predictive nomograms were established based on these risk factors for PTMC and LPTC patients, respectively. The accuracy and validity of our newly built models were verified by C-index and calibration curves. PTMC and LPTC patients with fewer than five positive CLN were each stratified into three subgroups based on their nomogram risk scores, and a detailed risk stratification flow chart was established for a more accurate evaluation of LLNM risk in PTC patients. Conclusions: A detailed stratification flow chart for PTC patients with CLNM to quantitatively assess LLNM risk was established, which may aid in clinical decision-making for those patients.

Exercise-Induced Excessive Blood Pressure Elevation Is Associated with Cardiac Dysfunction in Male Patients with Essential Hypertension.

Objective: Cardiopulmonary exercise testing (CPET) has been used to explore the blood pressure response and potential cardiovascular system structure and dysfunction in male patients with essential hypertension during exercise, to provide a scientific basis for safe and effective exercise rehabilitation and improvement of prognosis. Methods: A total of 100 male patients with essential hypertension (aged 18-60) who were admitted to the outpatient department of the Center for Diagnosis and Treatment of Cardiovascular Diseases of Jilin University from September 2018 to January 2021 were enrolled in this study. The patients had normal cardiac structure in resting state without clinical manifestations of heart failure or systematic regularization of treatment at the time of admission. Symptom-restricted CPET was performed and blood pressure was measured during and after exercise. According to Framingham criteria, male systolic blood pressure (SBP) ≥210 mmHg during exercise was defined as exercise hypertension (EH), and the subjects were divided into EH group (n = 47) and non-EH group (n = 53). Based on whether the oxygen pulse (VO2/HR) plateau appeared immediately after anaerobic threshold (AT), the EH group was further divided into the VO2/HR plateau immediately after AT (EH-ATP) group (n = 19) and EH-non-ATP group (n = 28). The basic clinical data and related parameters, key CPET indicators, were compared between groups. Result: Body mass index (BMI) visceral fat, resting SBP, and SBP variability in EH group were significantly higher than those in non-EH group. Moreover, VO2/HR at AT and the ratio of VO2/HR plateau appearing immediately after AT in EH group were significantly higher than those in the non-EH group. The resting SBP, 15-minute SBP variability, and the presence of VO2/HR plateau were independent risk factors for EH. In addition, work rate (WR) at AT but also WR, oxygen consumption per minute (VO2), VO2/kg, and VO2/HR at peak were significantly lower in the EH-ATP group compared to the EH-non-ATP group. Peak diastolic blood pressure (DBP) increment and decreased △VO2/△WR for AT to peak were independent risk factors for VO2/HR plateau appearing immediately after AT in EH patients. Conclusion: EH patients have impaired autonomic nervous function and are prone to exercise-induced cardiac dysfunction. EH patients with exercise-induced cardiac dysfunction have reduced peak cardiac output and exercise tolerance and impaired vascular diastolic function. CPET examination should be performed on EH patients and EH patients with exercise-induced cardiac dysfunction to develop precise drug therapy and effective individual exercise prescription, to avoid arteriosclerosis and exercise-induced cardiac damage. The retrospective study protocol was approved by medical ethics committee of the First Hospital of Jilin University (AF-IRB-032-06 No. 2021-015). The study was registered with the Chinese Clinical Trials Register, registration number: ChiCTR2100053140.

Circulating humanin is lower in coronary artery disease and is a prognostic biomarker for major cardiac events in humans.

BACKGROUND: Humanin is an endogenous mitochondria-derived peptide that plays critical roles in oxidative stress, inflammation and CAD. In this study, we measured the levels of circulating humanin, markers of oxidative stress and inflammation in patients with unstable angina and MI and studied the relationship between these parameters and major adverse cardiac events (MACE). METHODS: A total of 327 subjects were recruited from the inpatient department at First Hospital of Jilin University and divided into 3 groups [control, angina and myocardial infarction (MI)] based on the clinical data and the results of the angiography. Serum humanin and thiobarbituric acid reactive substances (TBARS) were measured at the time of initial admission. The hospitalization data and MACE of all patients were collected. RESULTS: Circulating humanin levels were lower in the angina group compared to controls [124.22 ±â€¯63.02 vs. 157.77 ±â€¯99.93 pg/ml, p < 0.05] and even lower in MI patients [67.17 ±â€¯24.35 pg/ml, p < 0.05 vs controls] and oxidative stress marker were higher in MI patients compared to the control and angina groups [12.94 ±â€¯4.55 vs. 8.26 ±â€¯1.66 vs. 9.06 ±â€¯2.47 umol/ml, p < 0.05]. Lower circulating humanin levels was an independent risk factor of MI patients. Circulating humanin levels could be used to predict MACE in angina group. CONCLUSIONS: Lower circulating humanin levels was an independent risk factor for CAD, and a potential prognostic marker for mild CAD. GENERAL SIGNIFICANCE: Humanin may become a new index for the diagnosis and treatment of CAD.

A positive feed-forward loop between Fusobacterium nucleatum and ethanol metabolism reprogramming drives laryngeal cancer progression and metastasis.

Alcohol consumption, which affects the structure and composition of the laryngeal microbiota, is one of the most important risk factors for laryngeal squamous cell cancer (LSCC). Our results demonstrated that high enrichment of Fusobacterium nucleatum (F. nucleatum) in LSCC was associated with poor prognosis. F. nucleatum increased miR-155-5p and miR-205-5p expression to suppress alcohol dehydrogenase 1B (ADH1B) and transforming growth factor ß receptor 2 (TGFBR2) expression by activating innate immune signaling, resulting in ethanol metabolism reprogramming to allow F. nucleatum accumulation and PI3K/AKT signaling pathway activation to promote epithelial-mesenchymal transition, further exacerbating the uncontrolled progression and metastasis of LSCC. Therefore, the positive feed-forward loop between F. nucleatum and ethanol metabolism reprogramming promotes cell proliferation, migration, and invasion to affect LSCC patient prognosis. The amount of F. nucleatum is a potential prognostic biomarker, which yields valuable insight into clinical management that may improve the oncologic outcome of patients with LSCC.

Mechanism and prevention strategy of a bidirectional relationship between heart failure and cancer (Review).

The relationship between cancer and heart failure has been extensively studied in the last decade. These studies have focused on describing heart injury caused by certain cancer treatments, including radiotherapy, chemotherapy and targeted therapy. Previous studies have demonstrated a higher incidence of cancer in patients with heart failure. Heart failure enhances an over-activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, and subsequently promotes cancer development. Other studies have found that heart failure and cancer both have a common pathological origin, flanked by chronic inflammation in certain organs. The present review aims to summarize and describe the recent discoveries, suggested mechanisms and relationships between heart failure and cancer. The current review provides more ideas on clinical prevention strategies according to the pathological mechanism involved.

Effect of early cardiac rehabilitation on prognosis in patients with heart failure following acute myocardial infarction.

OBJECTIVE: The purpose of this retrospective study is to evaluate the effectiveness of early cardiac rehabilitation on patients with heart failure following acute myocardial infarction. METHODS: Two hundred and thirty-two patients who developed heart failure following acute myocardial infarction were enrolled in this study. Patients were divided into heart failure with reduced ejection fraction group (n = 54) and heart failure with mid-range ejection fraction group (n = 178). Seventy-eight patients who accepted a two-week cardiac rehabilitation were further divided into two subgroups based on major adverse cardiovascular events. Key cardio-pulmonary exercise testing indicators that may affect the prognosis were identified among the cardiac rehabilitation patients. RESULTS: Early cardiac rehabilitation significantly reduced cardiac death and re-hospitalization in patients. There was more incidence of diabetes, hyperkalemia and low PETCO2 in the cardiac rehabilitation group who developed re-hospitalization. Low PETCO2 at anaerobic threshold (≤ 33.5 mmHg) was an independent risk factor for re-hospitalization. CONCLUSIONS: Early cardiac rehabilitation reduced major cardiac events in patients with heart failure following acute myocardial infarction. The lower PETCO2 at anaerobic threshold is an independent risk factor for re-hospitalization, and could be used as a evaluating hallmark for early cardiac rehabilitation.

Risk stratification of postoperative recurrence in hypopharyngeal squamous-cell carcinoma patients with nodal metastasis.

PURPOSE: To explore lymph node-related risk factors and investigate the benefit of different adjuvant therapy strategies in hypopharyngeal squamous-cell carcinoma (HPSCC) patients with nodal metastasis (N +). METHODS: We conducted a retrospective review covering 266 HPSCC patients with nodal metastasis. Kaplan-Meier curves and Cox proportional hazard models were utilized to evaluate recurrence-free survival (RFS) and independent risk factors. RESULTS: pT3-T4, extranodal extension, lymphovascular invasion, and lower lymph node involvement were high-risk factors leading to poorer RFS in N + HPSCC patients. Patients were classified into three groups based on the recursive-partitioning analysis (RPA). Postoperative chemoradiation significantly improved RFS in patients in the high-risk group (p < 0.001). For patients in the low- and intermediate-risk groups, the application of adjuvant therapies showed no significant benefit on RFS (p = 0.74 and 0.53, respectively). CONCLUSIONS: The novel risk stratification for N + HPSCC patients can predict the risk of postoperative recurrence effectively. Adjuvant chemoradiation is preferred for patients in the high-risk group as it lowers risk of recurrence. Conversely, for patients in the low- and intermediate-risk groups, regular observation and follow-up strategies are a valid form of treatment.

Diabetic mortality risk among cancer patients in the United State SEER population, 1975-2016.

BACKGROUND: The focus on diabetic mortality in cancer patients remains superficial. The objective of our study is to identify cancer patients with the highest risk of diabetic mortality compared with other cancer patients and the general US population. METHODS: The representative data of cancer patients dying from diabetes between 1975 and 2016 was retrieved from the Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMRs) and excess risks for multiple cancer sites were calculated. Cox regression analysis was performed to identify potential risk factors of death from diabetes. RESULTS: Among 9,043,788 cancer patients diagnosed between 1975 and 2016, 51,611 patients died from diabetes. the SMR of diabetic death was 2.15 compared with the general population. Malignancies of pancreas, liver, and brain had the highest SMR (>15) compared with the general population. The risk of death from diabetes was increasing in more recent years. The majority of deaths from diabetes occurred in those >45 years of age diagnosed with prostate, breast, colorectum, lung, or bladder cancer. Patients with older age, male sex, black race, higher histologic grade, unmarried status, and not undergoing surgery are at higher risk compared with other cancer survivors. CONCLUSIONS: Compared to the general population, cancer patients are at elevated risk of death from diabetes throughout the follow-up period. Elderly, black, unmarried males with distant metastases and without receiving surgery are recommended with earlier detection and more efficient diabetic care, especially for those with prostate, breast, colorectum, lung, or bladder cancer.

Combination of Exercise Training and SOD Mimetic Tempol Enhances Upregulation of Nitric Oxide Synthase in the Kidney of Spontaneously Hypertensive Rats.

Both exercise training (Ex) and superoxide dismutase (SOD) mimetic tempol have antihypertensive and renal protective effects in rodent models of several hypertensions. We recently reported that Ex increases nitric oxide (NO) production and the expression levels of endothelial and neuronal NO synthase (eNOS and nNOS) in the kidney and aorta of the spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). We also found that endogenous hydrogen peroxide (H2O2) upregulates the expression levels of eNOS and nNOS in SHR. To elucidate the mechanism of the Ex-upregulated NO system in the kidney, we examined the additive effect of Ex and tempol on the renal NO system in SHR and WKY. Our data showed that, in SHR, both Ex and tempol increase the levels of H2O2 and nitrate/nitrite (NOx) in plasma and urine. We also observed an increased renal NOS activity and upregulated expression levels of eNOS and nNOS with decreased NADPH oxidase activity. The effects of the combination of Ex and tempol on these variables were cumulate in SHR. On the other hand, we found that Ex increases these variables with increased renal NADPH oxidase activity, but tempol did not change these variables or affect the Ex-induced upregulation in the activity and expression of NOS in WKY. The SOD activity in the kidney and aorta was activated by tempol only in SHR, but not in WKY; whereas Ex increased SOD activity only in the aorta in both SHR and WKY. These results indicate that Ex-induced endogenous H2O2 produced in the blood vessel and other organs outside of the kidney may be carried to the kidney by blood flow and stimulates the NO system in the kidney.