A novel long non-coding RNA MIR4500HG003 promotes tumor metastasis through miR-483-3p-MMP9 axis in triple-negative breast cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.

Pressure injury risk factors in patients undergoing general anesthesia surgeries.

BACKGROUND: Pressure injuries result from prolonged pressure and lead to tissue damage, infections, extended recovery times, and an economic burden. PURPOSE: To explore risk factors for pressure injuries in patients who underwent surgery under general anesthesia. METHODS: This retrospective study included patients who underwent surgery at a regional educational hospital in southern Taiwan from January 1, 2018, through December 31, 2018. RESULTS: A comprehensive multivariate analysis was used to identify the prominent risk factors for pressure injury among the 11 231 patients enrolled in this study. These risk factors were an age of ≥65 years; surgery duration of >120 minutes; diastolic blood pressure of <60 mm Hg for >30 minutes during surgery; intraoperative use of dopamine, norepinephrine, or epinephrine as vasopressors; American Society of Anesthesiologists physical classification of III or higher; minimum intraoperative body temperature of ≤35°C; blood loss of >500 mL; and a supine or prone surgical position. CONCLUSIONS: This study identified several pressure injury risk factors related to surgical conditions and patient characteristics. Surgical teams must monitor, control, and manage these factors, prioritize staff education, and adopt preventive protocols.

High Prevalence of Cardiometabolic Risks and Health Needs Among Patients With Hepatocellular Carcinoma After Treatment: A Cross-sectional Study.

BACKGROUND: Many studies have indicated that inadequate health-related behavior is associated with the progression of cancer and cardiometabolic disorders. Because patients with hepatocellular carcinoma may adopt inadequate health behaviors, they are at risk for cancer recurrence, mortality, cardiometabolic disease progression, and worse quality of life. OBJECTIVE: To explore the prevalence of cardiometabolic risks and health-promoting behaviors associated with quality of life among patients with hepatocellular carcinoma after treatment. METHODS: A cross-sectional study was conducted from October 2021 to August 2022. Data were collected through face-to-face interviews using a structured questionnaire, and cardiometabolic information was recorded from medical charts. RESULTS: In total, 115 patients with liver cancer after treatment were enrolled; 73% were male. The mean age was 67.7 years, and high prevalence rates of central obesity (72.2%) and metabolic syndrome (47%) were noted. Inadequate exercise, oral hygiene, and cigarette smoking were common. The health-promoting score was significantly associated with exercise, the number of remaining teeth, and metabolic syndrome, which correlated with quality of life, including positive functional and negative symptoms dimensions. CONCLUSIONS: The findings demonstrated a high prevalence of cardiometabolic risks and inadequate health-related behaviors among patients with liver cancer after treatment. This study highlights the need for healthcare providers to help patients increase health literacy for preventing cardiometabolic risks at outpatient clinics. IMPLICATIONS FOR PRACTICE: Findings from this study can be used to advise healthcare providers to educate patients with liver cancer during and after treatment on improving their health-promoting behaviors.

Critical role of heme oxygenase-1 in chaetoglobosin A by triggering reactive oxygen species mediated mitochondrial apoptosis in colorectal cancer.

The incidence rate of colorectal cancer (CRC) has been increasing and poses severe threats to human health worldwide and developing effective treatment strategies remains an urgent task. In this study, Chaetoglobosin A (ChA), an endophytic fungal metabolite from the medicinal herb-derived fungus Chaetomium globosum Km1126, was identified as a potent and selective antitumor agent in human CRC. ChA induced growth inhibition of CRC cells in a concentration-dependent manner but did not impair the viability of normal colon cells. ChA triggered mitochondrial intrinsic and caspase-dependent apoptotic cell death. In addition, apoptosis antibody array analysis revealed that expression of Heme oxygenase-1 (HO-1) was significantly increased by ChA. Inhibition of HO-1 increased the sensitivity of CRC cells to ChA, suggesting HO-1 may play a protective role in ChA-mediated cell death. ChA induced cell apoptosis via the induction of reactive oxygen species (ROS) and ROS scavenger (NAC) prevented ChA-induced cell death, mitochondrial dysfunction, and HO-1 activation. ChA promoted the activation of c-Jun N-terminal kinase (JNK), and co-administration of JNK inhibitor or siRNA markedly reversed ChA-mediated apoptosis. ChA significantly decreased the tumor growth without eliciting any organ toxicity or affecting the body weight of the CRC xenograft mice. This is the first study to demonstrate that ChA exhibits promising anti-cancer properties against human CRC both in vitro and in vivo. ChA is a potential therapeutic agent worthy of further development in clinical trials for cancer treatment.

Comparison of medical resource consumption between oral cavity squamous cell carcinoma with and without sarcopenia: A nationwide population-based cohort study.

PURPOSE: No study has compared long-term medical resource consumption between patients with oral cavity squamous cell carcinoma (OCSCC) with and without sarcopenia receiving curative surgery. PATIENTS AND METHODS: Generalized linear mixed and logistic regression models were employed to evaluate the number of postoperative visits and medical reimbursement for head and neck cancer or complications and the number of hospitalizations for treatment-related complications over 5 years after curative surgery, respectively. RESULTS: The mean difference (95% CI) in total medical claims amounts between the nonsarcopenia and sarcopenia groups were new Taiwan dollars (NTD) 47 820 (35 864-59 776, p < 0.0001), 11 902 (4897-18 908, p = 0.0009), 17 282 (10 666-23 898, p < 0.0001), 17 364 (9644-25 084, p < 0.0001), and 8236 (111-16 362, p = 0.0470) for the first, second, third, fourth, and fifth years, respectively. CONCLUSION: The long-term medical resource consumption was higher in the sarcopenia group than in the nonsarcopenia group.

Association between serum carcinoembryonic antigen and cardiometabolic risks: Implication for cardiometabolic prevention.

Background: Serum carcinoembryonic antigen (CEA) is a biomarker commonly used to detect colorectal cancer. CEA levels are affected by many factors, including cardiometabolic diseases, such as cardiovascular diseases (CVDs) and diabetes. Cardiometabolic diseases and cancer share a similar pathological inflammatory pathway, which correlates with an unhealthy lifestyle. Hence, establishing an adequate CEA cut-off value might be a valuable reference for developing precision healthcare programs for cardiometabolic disease prevention. This study aimed to investigate the association between cardiometabolic risks and serum CEA and the underlying factors. Methods: A community-based, cross-sectional study was conducted between March and December 2021 on the western coast of Taiwan. Lifestyle data were assessed using a structured questionnaire. The cardiometabolic biomarkers, serum CEA, urine malondialdehyde, and 1-hydroxypyrene were quantified by the central laboratory of the collaborating hospital. Chi-square and binary multivariable logistic regression implemented in R version 4.0.2 were used to identify factors defining the risk of high serum CEA levels. Results: A total of 6,295 adult residents without cancer-related diseases completed the study. The mean age was 48.6 (SD = 16.4) years, 56% were female, 32% had metabolic syndrome, and 23% and 10% had CVDs and diabetes, respectively. Multivariate logistic regression showed that age ≥ 65 years, male sex, alcohol consumption, smoking, infrequent use of dental floss, fewer remaining teeth, CVDs, diabetes, and oxidative stress were significantly associated with serum CEA ≥ 3 ng/mL. The discriminatory performance of the area under the receiver operating characteristic curve was 0.75 (0.73-0.76), showing that this model was suitable for distinguishing high CEA levels. Conclusion: Our findings highlight the importance of understanding cardiometabolic diseases, unhealthy lifestyles, and oxidative stress, which contribute to high serum CEA. This study demonstrates that CEA, a well-known tumor marker, can help the early detection and prevention of cardiometabolic diseases via personalized lifestyle modification.

Non-Contrast-Enhanced MR Arteriography of Potential Living-Related Liver Donor: Using Contrast Enhanced CT Arteriography as Standard Reference.

BACKGROUND: Contrast-enhanced computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the primary modalities to assess donors' vessels before transplant surgery. Radiation and contrast medium are potentially harmful to donors. PURPOSE: To compare the image quality and visualization scores of hepatic arteries on CTA and balanced steady-state free-precession (bSSFP) non-contrast-enhanced MRA (NC-MRA), and to evaluate if bSSFP NC-MRA can potentially be a substitute for CTA. STUDY TYPE: Prospective. POPULATION: Fifty-six consecutive potential living-related liver donors (30.9 ± 8.4 years; 31 men). FIELD STRENGTH/SEQUENCE: 1.5T; four bSSFP NC-MRA sequences: respiratory-triggered (Inhance inflow inversion recovery [IFIR]) and three breath-hold (BH); and CTA. ASSESSMENT: The artery-to-liver contrast (Ca-l) was quantified. Three radiologists independently assigned visualization scores using a four-point scale to potential origins, segments, and branches of the hepatic arteries, determined the anatomical variants based on Hiatt's classification, and assessed the image quality of NC-MRA sequences. STATISTICAL TESTS: Fleiss' kappa to evaluate the readers' agreement. Repeat measured ANOVA or Friedman test to compare Ca-l of each NC-MRA. Friedman test to compare overall image quality and visualization scores; post hoc analysis using Wilcoxon signed-rank test. P-value <0.05 was considered statistically significant. RESULTS: Inhance IFIR Ca-l was significantly higher than all BH bSSFP Ca-l (0.56 [0.45-0.64] vs. 0.37 [0.29-0.47] to 0.41 [0.23-0.51]). Overall image quality score of BH bSSFP TI1200 was significantly higher than other NC-MRA (4 [4-4] vs. 4 [3 to 4-4]). The median visualization scores of almost all arteries on CTA were significantly higher than on NC-MRA (4 [3 to 4-4] vs. 1 [1-2] to 4 [4-4]). The median visualization scores were all 4 [4-4 ] on Inhance IFIR with >92.3% observed scores ≥3, except the segment 4 branch (3 [1-4], 53.6%). The identification rates of arterial variants were 92.9%-97% on Inhance IFIR. DATA CONCLUSIONS: Although CTA is superior to the NC-MRA, all NC-MRA depict the donor arterial anatomy well. Inhance IFIR can potentially be an alternative image modality for CTA to evaluate the arterial variants of living donors. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Comparison of surgical complications after curative surgery in patients with oral cavity squamous cell carcinoma and sarcopenia.

BACKGROUND: The study aims to clarify the association of sarcopenia with perioperative and postoperative complications in oral cavity squamous cell carcinoma (OCSCC) patients undergoing curative surgery and to understand the reasons causing the poor oncologic outcomes for OCSCC. METHODS: We conducted a propensity score matching study to investigate the association of perioperative and postoperative outcomes in OCSCC patients with sarcopenia and without sarcopenia. A retrospective analysis of a large national data set from the Taiwan Cancer Registry Database was conducted. At least two claims for patients with a principal diagnosis of sarcopenia within the 12-month preoperative period were defined as the criteria for sarcopenia diagnosis (ICD-10-CM code M62.84). Sarcopenia was diagnosed through the measurement of low muscle strength and low muscle mass by any one of the patient's attending orthopaedic physician, rehabilitation physician, family medicine specialist or geriatrician. A multivariate logistic regression model was used to calculate the perioperative, and postoperative major complications. RESULTS: Our final cohort included 16 293 patients with OCSCC (10 862 and 5 431 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for further analysis. The sarcopenia group was 10.40% female and 89.60% male, and the nonsarcopenia group was 9.74% female and 90.26% male. The mean age ± standard deviation (SD) were 56.44 ± 11.14 and 56.22 ± 11.29 for sarcopenia and nonsarcopenia groups. OCSCC patients with sarcopenia undergoing curative surgery had a significantly higher blood transfusion rate and volume; longer intensive care unit (ICU) stay, and hospital stay; higher postoperative 30-day mortality (adjusted odds ratio [aOR]: 1.12, 95% confidence interval [CI] [1.07, 1.56]) and rates of pneumonia (aOR: 1.34, 95% CI [1.20, 1.50]), acute renal failure (aOR: 1.45, 95% CI [1.12, 1.87]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]); higher postoperative first-year mortality (aOR: 1.18, 95% CI [1.13, 1.51]) and rates of pneumonia (aOR: 1.43, 95% CI [1.30, 1.56]), acute myocardial infarction (aOR: 1.52, 95% CI [1.06, 2.18]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]). CONCLUSIONS: OCSCC patients with sarcopenia might exhibit more perioperative and surgical complications than those without sarcopenia.

Correlations among lean tissue index, physical activity, clinical parameters, diet quality, and nutritional status in patients receiving haemodialyses.

INTRODUCTION: Poor diet quality and malnutrition accelerate protein and energy depletion. This can result in a diminished lean tissue index (LTI) and an inability to perform daily activities, both of which increase the risk of falls and affect the quality of life. OBJECTIVE: This study investigated the correlations among LTI, physical activity (PA), clinical parameters, diet quality, and nutritional status. METHODS: A cross-sectional study design was employed. Participants in stable conditions receiving haemodialyses were enroled. LTI was measured using a body composition monitor. Three-day dietary records and demographic and clinical parameters were collected. RESULTS: In total, 104 patients receiving haemodialyses were recruited (53.8% men, aged 57.7 ± 11.78 years; dialysis duration, 7.3 ± 6.04 years). LTI was not associated with diet quality; LTI was positively correlated with sex and negatively correlated with age, dialysis duration, and fat tissue index (FTI); and lean tissue index was positively correlated with PA. Among patients with a normal LTI, the odds ratio for low-FTI was 31.04 times higher than that for high-FTI. In total, 80.8% of the participants had poor diet quality, which was mainly attributed to their excessive intake of saturated fatty acids and insufficient fruit intake. CONCLUSIONS: Although diet quality was unrelated to the LTI, the results indicated that most patients receiving haemodialyses had poor diet quality. Therefore, this topic merits further investigation.

A novel nomogram for predicting cardiometabolic diseases from modifiable risks in middle-aged adults-implication for health education.

Background: Middle-aged adults often overlook critical modifiable risk factors that contribute to the emergence of cardiometabolic diseases (CMDs), including hypertension and diabetes. Many CMDs can be alleviated by addressing these modifiable risks. However, there has been insufficient research focused on rural adults with lower levels of health literacy in this regard. The aim of this study was to explore and develop an intuitive assessment tool for predicting cardiometabolic diseases (CMDs), which can be used for health education with adults of low health literacy. Methods: This was a community-based, cross-sectional study. A structured questionnaire on health-promoting habits, smoking, sleep, and physiological biomarkers was obtained via community health screening in the coastal region of Yunlin County, Taiwan. Multivariate logistic regression was used to screen for significant variables in the nomogram construction. Analysis with nonlinear restricted cubic spline was performed. Results: A total of 712 participants (60.9% females) aged 40-64 years, with middle school level or lower education, were included. The average age was 55.6 years (SD=7.3), and 220 individuals (31%) had CMDs. Multivariate logistic regression analysis revealed that age, lower scores of vegetables, fruit, water, and exercise (VFWE), smoking history, sleep deprivation, and being overweight were significantly associated with CMDs. The model incorporating these modifiable risk factors demonstrated good discriminatory ability, as indicated by an area under the receiver operating characteristic curve of 0.75 (0.73-0.76). A predictive nomogram was developed that presented modifiable risk factors in a simple graphical format to facilitate the prediction of CMDs. Conclusions: This study highlights a high prevalence of CMDs among middle-aged adults, along with the disregard for important risk factors that could be modified. The developed nomogram could be a practical and effective tool for community health education to enhance health literacy and prevent the progression of CMDs.

Anti-Epstein-Barr Viral Agents from the Medicinal Herb-Derived Fungus Alternaria alstroemeriae Km2286.

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-9. Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A-D (1-4), along with altertoxin IV (5), altertoxin VIII (6), stemphyperylenol (7), tenuazonic acid (8), and allo-tenuazonic acid (9). Compounds 1-6 exhibited antiviral activities against Epstein-Barr virus (EBV) with EC50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 µM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1-4, 6, and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 µM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.

Interfacial nanoarchitectonics for ZIF-8 membranes with enhanced gas separation.

Metal-organic framework (MOF) membranes are potentially useful in gas separation applications. Conventional methods of MOF membrane preparation require multiple steps and high-pressure conditions. In this study, a reliable one-step interfacial synthesis method under atmospheric pressure has been developed to prepare zeolitic imidazolate framework-8 (ZIF-8) membranes supported on porous α-Al2O3 disks. To obtain optimal ZIF-8 membranes, three reaction parameters were investigated, namely, reaction temperature, reaction time, and concentration of the organic linker (i.e., 2-methylimidazole). The growth of ZIF-8 membranes under various parameters was evaluated by field-emission scanning electron microscopy, and the optimal synthesis conditions were determined (i.e., 80 °C for 12 h in 50 mM of 2-methylimidazole). The as-synthesized ZIF-8 membranes were then applied to CO2/N2 gas separation, which exhibited a maximum separation factor of 5.49 and CO2 gas permeance of 0.47 × 10-7 mol·m-2·s-1·Pa-1.

Number of negative lymph nodes with a positive impact on survival of stage III colon cancer; a retrospective observation study for right side and left side colon.

BACKGROUND: The purpose was to examine the effect of negative lymph nodes (NLN) number on survival in stage III colon cancer. To reduce the interference of acute inflammation, we included patients with stage III colon cancer who had undergone elective surgery and excluded those who had tumor perforation, obstruction, ischemia, or massive tumor bleeding. METHODS: This retrospective cohort study included 2244 patients with stage III colon cancer between 1995 and 2016 at a single center. The effect of NLN on 5-year relapse-free survival (RFS), 5-year overall survival (OS), and comparison of multivariate factors was assessed according to tumor locations. RESULTS: The two optimal cutoff values of NLN for proximal and distal colon, namely 27 and 12, were determined by plotting the time-dependent receiver operating characteristic curve. Overall, 499 of 891 and 1020 of 1353 patients with right-side and left-side colon cancer, respectively, had high NLN. In right-side colon cancer, patients with high NLN (≥ 27) had superior OS (74.9% vs. 62.7%, P <  0.001) and RFS (75.0% vs. 61.9%, P <  0.001) than did those with low NLN. Moreover, in left-side colon cancer, patients with high NLN (≥12) experienced significantly superior OS (80.8% vs. 68.6%, P <  0.001) and RFS (77.3% vs. 66.2%, P <  0.001) than did those with low NLN. Among the different subgroups of stage III colon cancer, the high NLN group showed significantly superior RFS and OS in stage IIIB (RFS: 77.0% vs. 68.0%, P = 0.001; OS: 78.6% vs. 67.9%, P <  0.001) and IIIC (RFS: 58.2% vs. 44.1%, P = 0.001; OS: 65.7% vs. 51.1%, P <  0.001) colon cancer. However, in stage IIIA colon cancer, high NLN only showed survival benefit in OS (91.5% vs. 89.8%, P = 0.041). Multivariate analyses confirmed that high NLN, high carcinoembryonic antigen (≥ 5 ng/mL) level, and stage IIIC status are three independent prognostic factors in both the proximal and distal colon. CONCLUSIONS: NLN is a crucial prognostic factor for stage III colon cancer in various tumor locations or in the subgroups of stage III disease. In advanced stage III colon cancer, the importance of NLN and its role in anti-cancer immune response could be highlighted.

Exploring Volatile Organic Compounds in Breath for High-Accuracy Prediction of Lung Cancer.

(1) Background: Lung cancer is silent in its early stages and fatal in its advanced stages. The current examinations for lung cancer are usually based on imaging. Conventional chest X-rays lack accuracy, and chest computed tomography (CT) is associated with radiation exposure and cost, limiting screening effectiveness. Breathomics, a noninvasive strategy, has recently been studied extensively. Volatile organic compounds (VOCs) derived from human breath can reflect metabolic changes caused by diseases and possibly serve as biomarkers of lung cancer. (2) Methods: The selected ion flow tube mass spectrometry (SIFT-MS) technique was used to quantitatively analyze 116 VOCs in breath samples from 148 patients with histologically confirmed lung cancers and 168 healthy volunteers. We used eXtreme Gradient Boosting (XGBoost), a machine learning method, to build a model for predicting lung cancer occurrence based on quantitative VOC measurements. (3) Results: The proposed prediction model achieved better performance than other previous approaches, with an accuracy, sensitivity, specificity, and area under the curve (AUC) of 0.89, 0.82, 0.94, and 0.95, respectively. When we further adjusted the confounding effect of environmental VOCs on the relationship between participants' exhaled VOCs and lung cancer occurrence, our model was improved to reach 0.92 accuracy, 0.96 sensitivity, 0.88 specificity, and 0.98 AUC. (4) Conclusion: A quantitative VOCs databank integrated with the application of an XGBoost classifier provides a persuasive platform for lung cancer prediction.

Effect of ß-Blocker in Treatment-Naïve Patients With Advanced Lung Adenocarcinoma Receiving First-Generation EGFR-TKIs.

BACKGROUND: Through activation of adrenergic receptors, chronic stress can trigger the secretion of neurotransmitters and hormones that enhance tumor growth, increase angiogenesis, and promote drug resistance. This study aimed to evaluate the effect of ß-blockers in patients receiving first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for lung adenocarcinoma. METHODS: This retrospective cohort study enrolled patients with advanced lung adenocarcinoma under first-line EGFR-TKIs between 2011 and 2014 in the National Health Insurance Research Database of Taiwan. The effects of ß-blockers use, defined as ≥60 defined daily doses within 180 days before initiation of EGFR-TKI therapy, on the 2-year time-to-discontinuation (TTD) of EGFR-TKIs and 4-year overall survival (OS) were investigated using Cox regression analyses with inverse propensity score weighting and sensitivity analysis in subgroup with either hypertension or ischemic heart diseases. RESULTS: Among 4988 enrolled patients, 552 (11.1%) were in the ß-blocker group. Patients in the ß-blocker group were more likely to be older than 75 and had diabetes mellitus and cardiovascular comorbidities. In Cox regression analysis, ß-blocker usage was associated with a longer TTD (hazard ratio, HR: 0.91 [0.86-0.96]) and OS (HR: 0.68 [0.64-0.72]). The results also favored ß-blocker group in sensitivity analysis. CONCLUSIONS: In treatment-naïve patients with advanced lung adenocarcinoma under first-line EGFR-TKIs, prior use of ß-blocker was associated with a better outcome. The findings encourage further prospective clinical study to validate the possibility of ß-blockers as adjuvant anticancer therapy.

Metformin Attenuates Osteoporosis in Diabetic Patients with Carcinoma in Situ: A Nationwide, Retrospective, Matched-Cohort Study in Taiwan.

Patients with diabetes are at increased risk of cancer development and osteoporosis. Metformin is an effective agent for diabetes management. Epidemiological studies have identified an association between metformin use and cancer prevention. This article outlines the potential for metformin to attenuate the rate of osteoporosis in diabetic patients with carcinoma in situ (CIS). From the National Health Insurance Research Database of Taiwan, 7827 patients with diabetes with CIS who were receiving metformin therapy were selected, along with 23,481 patients as 1:3 sex-, age- and index year-matched controls, who were not receiving metformin therapy. A Cox proportional hazard analysis was used to compare the rate of osteoporosis during an average of 15-year follow-up. Of the subjects who were enrolled, 801 (2.56%) had osteoporosis, including 168 from the metformin group (2.15%) and 633 from the without metformin group (2.70%). The metformin group presented a lower rate of osteoporosis at the end of follow-up (p = 0.009). The Cox proportional hazard regression analysis revealed a lower rate of osteoporosis for the metformin group (adjusted hazard ratio of 0.820; 95% confidence interval = 0.691-0.972, p = 0.022). Diabetic patients with CIS under metformin therapy presented lower osteoporosis rate than those who were not receiving metformin therapy.

Treatment Options of First-Line Tyrosine Kinase Inhibitors and Subsequent Systemic Chemotherapy Agents for Advanced EGFR Mutant Lung Adenocarcinoma Patients: Implications From Taiwan Cancer Registry Cohort.

OBJECTIVES: Large-scale, population-based real-world studies on the treatment outcomes of first-line tyrosine kinase inhibitors (TKIs) and subsequent systemic chemotherapy agents for lung adenocarcinoma (with activating epidermal growth factor receptor [EGFR] mutations) remain limited. MATERIALS AND METHODS: From March 2014 to December 2016, patients with advanced lung adenocarcinoma, identified from the Taiwan Cancer Registry were included in this study if they received any of the three TKIs as first-line treatment. The primary outcome was overall survival (OS). The secondary outcome was time-to-treatment discontinuation (TTD). RESULTS: A total of 4,889 patients (median age: 67 years and two-thirds with distant metastasis) were recruited (1,778 gefitinib, 1,599 erlotinib, and 1,512 afatinib users). A 1:1 propensity score (PS)-matched cohorts of 1,228 afatinib/erlotinib and 1054 afatinib/gefitinib was created. After PS matching, it was found that afatinib was not associated with better OS (afatinib vs. erlotinib, HR: 0.96, 95% CI: 0.86-1.07; afatinib vs. gefitinib, HR: 0.91, 95% CI: 0.81-1.02). In the subgroup analysis, afatinib demonstrated a survival benefit in patients with active smoking (afatinib vs. erlotinib, HR: 0.69, 95% CI: 0.51-0.93; afatinib vs. gefitinib, HR: 0.67, 95% CI: 0.48-0.94) and ECOG > 1 (afatinib vs. erlotinib, HR: 0.79, 95% CI: 0.63-0.99; afatinib vs. gefitinib, HR: 0.78, 95% CI: 0.62-0.98). A total of 41.1% (n = 1992) of first-line TKI users received subsequent chemotherapy. Among the three TKI groups, pemetrexed usage was associated with better OS compared with other chemotherapy agents, with the exception of gemcitabine in the afatinib and gefitinib groups. Pemetrexed and gemcitabine had the longest TTD of 3-4 months. CONCLUSIONS: Among patients with EGFR mutant lung adenocarcinoma, afatinib use may not provide longer OS compared with first-generation TKIs. Afatinib may be preferably considered among patients with active smoking and should not be withheld among those with worse performance status. With 40% of patients receiving subsequent chemotherapy, pemetrexed may be the preferred agent, while gemcitabine can be a reasonable alternative.

Changes in hypothermal stress-induced hepatic mitochondrial metabolic patterns between fresh water- and seawater-acclimated milkfish, Chanos chanos.

Milkfish (Chanos chanos) is a tropical euryhaline species. It can acclimate to fresh water (FW) or seawater (SW) and be cultured in both. In winter, cold snaps cause huge losses in milkfish revenue. Compared to FW-acclimated individuals, SW-acclimated milkfish have better low-temperature tolerance. Under hypothermal stress, a stable energy supply is critical to maintain normal liver function. In this study, the levels of key mitochondrial enzymes (citrate synthase (CS) and cytochrome c oxidase (COX)) in milkfish livers were examined. The CS:COX activity ratio in FW milkfish significantly increased under hypothermal stress (18 °C) whereas ATP (the end product of aerobic metabolism) was downregulated. Therefore, the activities of the enzymes involved in mitochondrial amino acid biosynthesis (aspartate aminotransferase (AST) and glutamate dehydrogenase (GDH)) were evaluated to elucidate energy flow in milkfish livers under hypothermal stress. In FW milkfish, GDH activity was upregulated whereas AST activity was downregulated. Nevertheless, the levels of all the aforementioned enzymes did not significantly change in SW milkfish under hypothermal stress. In summary, we clarified the mechanism accounting for the fact that SW milkfish have superior low-temperature tolerance to FW milkfish and demonstrated that SW and FW milkfish have different and unique strategies for regulating energy flow.

Differed IL-1 Beta Response between Active TB and LTBI Cases by Ex Vivo Stimulation of Human Monocyte-Derived Macrophage with TB-Specific Antigen.

BACKGROUND: The difference of macrophage-specific interleukin-1 beta (IL-1b) response between latent tuberculosis infection (LTBI) and active tuberculosis (TB) remains less studied. METHOD: We performed this prospective study and recruited active TB patients, contacts with LTBI, and uninfected contacts. The gene and protein expression of human monocyte-derived macrophage (hMDM) after ex vivo stimulation by early secretory antigenic target-6KD (ESAT-6) and tuberculin purified protein derivatives (PPD) was studied by real-time PCR and flow cytometry. The effect of caspase-1 inhibitor was also studied. RESULT: The IL-1b gene expression after 6 hr ESAT-6 1 µg/ml stimulation was different among active TB patients (n = 12), LTBI cases (n = 12), and uninfected contacts (n = 23) (log fold change: 0.98 ± 1.26 vs. 2.20 ± 0.96 vs. 2.20 ± 0.96, P = 0.013). The IL-1b gene expression at 24 hours was higher than that at 6 hours in LTBI cases (n = 4) and uninfected contacts (n = 6). After 24 hr ESAT-6 1 µg/ml stimulation, the percentage of IL-1b-expressed hMDM was borderline lower in the active TB patients (n = 9) than in the LTBI cases (n = 10) (14.0 ± 11.2% vs. 31.6 ± 22.5%, P = 0.065). Compared with ESAT-6 1 µg/ml stimulation but without the addition of caspase-1 inhibitor (CasI) (55.6 ± 16.3%), the percentage of IL-1b-positive hMDMs decreased after addition of CasI (50 µg/ml CasI: 49.8 ± 18.2%, P = 0.078; 100 µg/ml CasI: 46.6 ± 20.8%, P = 0.030; 150 µg/ml CasI: 33.7 ± 15.5%, P = 0.016). CONCLUSIONS: This study revealed that macrophage-specific IL-1b response differed among different stages of Mycobacterium tuberculosis infection. The role of IL-1b and inflammasome in the process of LTBI progressing to active TB warrants further investigation.

High-Performance Sensor Based on Thin-Film Metallic Glass/Ultra-nanocrystalline Diamond/ZnO Nanorod Heterostructures for Detection of Hydrogen Gas at Room Temperature.

This article outlines a novel material to enable the detection of hydrogen gas. The material combines thin-film metallic glass (TFMG), ultra-nanocrystalline diamond (UNCD), and ZnO nanorods (ZNRs) and can be used as a device for effective hydrogen gas sensing. Three sensors were fabricated by using combinations of pure ZNRs (Z), UNCD/ZNRs (DZ), and TFMG/UNCD/ZNRs (MDZ). The MDZ device exhibited a performance superior to the other configurations, with a sensing response of 34 % under very low hydrogen gas concentrations (10 ppm) at room temperature. Remarkably, the MDZ-based sensor exhibits an ultra-high sensitivity of 60.5 % under 500 ppm H2 . The MDZ sensor proved very fast in terms of response time (20 s) and recovery time (35 s). In terms of selectivity, the sensors were particularly suited to hydrogen gas. The sensor achieved the same response performance even after two months, thereby demonstrating the superior stability. It is postulated that the superior performance of MDZ can be attributed to defect-related adsorption as well as charge carrier density. This paper also discusses the respective energy band models of these heterostructures and also the interface effect on the gas sensing enhancements. The results indicate that the proposed hybrid TFMG/UNCD/ZNRs nanostructures could be utilized as high-performance hydrogen gas sensors.