Continuous Superior Trunk Block versus Single-Shot Superior Trunk Block with Intravenous Dexmedetomidine for Postoperative Analgesia in Arthroscopic Shoulder Surgery: A Prospective Randomized Controlled Trial.

Background/Objectives: Intravenous dexmedetomidine (DEX) can increase the analgesia duration of peripheral nerve block; however, its effect in combination with superior trunk block (STB) remains unclear. We examined whether combining single-shot STB (SSTB) with intravenous DEX would provide noninferior postoperative analgesia comparable to that provided by continuous STB (CSTB). Methods: Ninety-two patients scheduled for elective arthroscopic rotator cuff repair were enrolled in this prospective randomized trial. Patients were randomly assigned to the CSTB or SSTB + DEX group. Postoperatively, each CSTB group patient received 15 mL of 0.5% ropivacaine and a continuous 0.2% ropivacaine infusion. Each SSTB group patient received a 15 mL postoperative bolus injection of 0.5% ropivacaine. DEX was administered at 2 mcg/kg for 30 min post anesthesia, then maintained at 0.5 mcg/kg/h till surgery ended. Pain scores were investigated every 12 h for 48 h post operation, with evaluation of rebound pain incidence and opioid consumption. Results: The SSTB + DEX group had significantly higher median pain scores at 12 h post operation (resting pain, 8.0 vs. 3.0; movement pain, 8.0 vs. 5.0) and a higher incidence of rebound pain (56% vs. 20%) than the CSTB group. However, no significant between-group differences were observed in pain scores postoperatively at 24, 36, or 48 h. The CSTB group required less opioids and fewer rescue analgesics within 12-24 h post operation than the SSTB + DEX group. Conclusions: Compared with CSTB, SSTB + DEX required additional adjuvant or multimodal analgesics to reduce the risk and intensity of postoperative rebound pain in patients who underwent arthroscopic rotator cuff repair.

Long-term impact of weight loss in people with class II obesity on the overall burden of disease: evidence from the national health screening cohort in Korea.

BACKGROUND: Obesity is known to increase overall disease burden but does obesity management actually help reduce disease burden? OBJECTIVES: To investigate the effects of weight loss on disease burden in people with obesity using the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in Korea. SETTING: Pure longitudinal observational study using Nationwide cohort database. METHODS: Out of 514,866 NHIS-HEALS cohort, participants with class II obesity in Asia-Pacific region (30 ≤ body mass index [BMI] < 35) who underwent health check-up provided by NHIS during 2003-2004 (index date) were included. All final participants continued to receive a total of 5 biennial health check-ups over the next 10 years without missing. A group-based trajectory model (GBTM) was used to categorize subjects based on 10-year BMI change patterns. The changes of co-morbidities, healthcare resource utilization, and medical cost were analyzed. RESULTS: The final study subjects (9857) were categorized into 3 trajectory clusters based on the pattern of BMI (kg/m2) change: maintenance (57.35%) with an average change of -.02 ± .06, loss (38.65%) with -.04 ± .08, and substantial loss (4.0%) with -.10 ± .18. The annual increases in the number of co-morbidities per subject in each cluster were .18, .18, and .16 (all P < .001), respectively. The increase of healthcare resource utilization over time was lowest for the substantial loss compared to maintenance and loss. With each passing year, the average annual total healthcare cost increased by ₩21,200 ($16.48, P = .034) and ₩10,500 ($8.16, P = .498) in the maintenance and loss, respectively, but decreased by ₩62,500 ($48.59, P = .032) in the substantial loss. CONCLUSIONS: Weight loss in people with obesity was associated with a reduced burden of disease, as evidenced by lower co-morbidity, healthcare resource utilization rate, and decreased medical costs. This study highlights the potential positive long-term impact on Korean society when actively managing weight in individuals with obesity.

Potential risk of proton pump inhibitors for Parkinson's disease: A nationwide nested case-control study.

Proton pump inhibitor (PPI) use is a potential risk factor for neurodegenerative disease development; however, its role in Parkinson's disease (PD) remains unclear. This study aimed to investigate the association between PPI use and PD risk. A total of 31,326 patients with newly diagnosed PD were matches by age, sex, body mass index, diabetes, and hypertension with 125,304 controls at a ratio of 1:4. The data were collected from the Korean National Health Insurance Services Database from January 2010 to December 2019. Cumulative defined daily doses of PPIs were extracted from treatment claims. We examined the association between PPI use and PD risk using conditional logistic regression. To prevent protopathic bias, we excluded patients diagnosed with PD within a 1-year lag period after PPI exposure. We applied 2- and 3-year lag periods for sensitivity analysis. PPI use was associated with an increased risk of PD when a 1-year lag period was applied between PPI exposure and PD development (adjusted odds ratio, 1.10; 95% confidence interval, 1.07-1.13). A significant positive dose-response relationship existed between the cumulative defined daily doses of PPIs and PD development (P<0.001). Similar results were obtained for the 2- or 3-year lag periods. The association did not vary based on gender. Older age, a higher Charlson Comorbidity Index score, no alcohol consumption, and a non-smoking status were associated with a significantly increased PD risk with PPI use. We observed an association between PPI use and PD risk, although long-term follow-up studies are necessary to verify this association.

Ultrasound estimates of the epidural depth in the paramedian sagittal oblique and transverse median planes: the correlation between estimated and actual depth to the epidural space in children with scoliosis.

INTRODUCTION: The present study aimed to compare the correlation and agreement of epidural depth estimation using ultrasound in the paramedian sagittal oblique (PSO) versus the transverse median (TM) plane relative to the actual epidural depth observed during midline epidural punctures in children with scoliosis. METHODS: In this prospective observational study, we enrolled 55 children aged 3-14 years with thoracolumbar scoliosis (Cobb angle >10°) requesting postoperative epidural analgesia. Ultrasound imaging was performed to estimate the distance from the skin to the epidural space in the bilateral PSO and TM planes. An anesthesiologist performed midline epidural puncture and measured the actual epidural depth from the skin to the epidural space. The correlation and degree of agreement between the ultrasound-estimated and actual epidural depths were investigated using Pearson's and concordance correlation coefficients. The image quality of the ligamentum flavum and posterior dura mater was compared. RESULTS: In the PSO view, where the larger of the two measurements from both sides was used, both Pearson's and concordance correlation coefficients for comparing the actual epidural and ultrasound-estimated depths were significantly higher than those in the TM view (0.964 vs 0.930, p value=0.002; 0.952 vs 0.892, p value=0.004, respectively). The ligamentum flavum-posterior dura mater unit was more easily distinguished in the PSO view than in the TM view (72.7% vs 38.2%, p value<0.001). CONCLUSIONS: The PSO view can be a reliable guide to facilitate epidural puncture in children with scoliosis with better visualization. TRIAL REGISTRATION NUMBER: NCT04877964.

Repurposing Metabolic Inhibitors in the Treatment of Colon Adenocarcinoma Patient-Derived Models.

The effect of agonists on AMP-activated protein kinase (AMPK), mainly metformin and phenformin, has been appreciated in the treatment of multiple types of tumors. Specifically, the antitumor activity of phenformin has been demonstrated in melanomas containing the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) activating mutation. In this report, we elucidated the synergistic antitumor effects of biguanides with metabolism inhibitors on colon tumors. Phenformin with 2-deoxy-D-glucose (2DG) inhibited tumor cell growth in cancer cell lines, including HT29 cells harboring BRAF- and p53-mutations. Biochemical analyses showed that two chemotherapeutics exerted cooperative effects to reduce tumor growth through cell cycle arrest, apoptosis, and autophagy. The drugs demonstrated activity against phosphorylated ERK and the gain-of-function p53 mutant protein. To demonstrate tumor regressive effects in vivo, we established patient-derived models, including xenograft (PDX) and organoids (PDO). Co-treatment of biguanides with chemotherapeutics efficiently reduced the growth of patient-derived colon models in comparison to treatment with a single agent. These results strongly suggest that significant therapeutic advantages would be achieved by combining AMPK activators such as phenformin and cancer metabolic inhibitors such as 2DG.

Hemo-metabolic impairment in patients with ST-segment elevation myocardial infarction: Data from the INTERSTELLAR registry.

BACKGROUND: Not only hemo-dynamic (HD) factors but also hemo-metabolic (HM) risk factors reflecting multi-organ injuries are considered as important prognostic factors in ST-segment elevation myocardial infarction (STEMI). However, studies regarding HM risk factors in STEMI patients are currently limited. METHOD: Under analysis were 1,524 patients with STEMI who underwent primary percutaneous coronary intervention in the INTERSTELLAR registry. Patients were divided into HM (≥ 2 risk factors) and non-HM impairment groups. The primary outcome was in-hospital all-cause mortality, and the secondary outcome was 1-year all-cause mortality. RESULTS: Of 1,524 patients, 214 (14.0%) and 1,310 (86.0%) patients were in the HM and non-HM impairment groups, respectively. Patients with HM impairment had a higher incidence of in-hospital mortality than those without (24.3% vs. 2.7%, p < 0.001). After adjusting for confounders, HM impairment was independently associated with in-hospital mortality (inverse probability of treatment weighting [IPTW]-adjusted odds ratio: 1.81, 95% confidence interval: 1.08-3.14). In the third door-to-balloon (DTB) time tertile (≥ 82 min), HM impairment was strongly associated with in-hospital mortality. In the first DTB time tertile ( < 62 min), indicating relatively rapid revascularization, HM impairment was consistently associated with increased in-hospital mortality. CONCLUSIONS: Hemo-metabolic impairment is significantly associated with increased risk of in-hospital and 1-year mortality in patients with STEMI. It remains a significant prognostic factor, regardless of DTB time.

Real-world survival after colorectal surgery for malignancy in Korean patients with chronic kidney disease: an analysis of Korean healthcare big data, 2002-2019.

Purpose: Globally, chronic kidney disease (CKD) is common and has been associated with an increased risk of colorectal cancer (CRC). There is a dearth of literature on the real-world morbidity and mortality associated with CKD comorbid with CRC. This study was performed to evaluate real-world survival outcomes of colorectal malignancy in Korean CKD patients. Methods: The National Health Insurance Service of Korea provided data on patients who underwent surgical resection among patients diagnosed with CRC from 2002 to 2019. Results: A total of 219,550 patients were included: 6,181 patients with underlying CKD and 213,369 patients without it. Each morbidity was significantly higher in the CKD-CRC group, and the postoperative mortality rates for the 30-day (3.11% vs. 1.78%, P < 0.001), 60-day (5.95% vs. 3.83%, P < 0.001), and 90-day mortality rate (8.12% vs. 5.32%, P < 0.001) were significantly higher in the CKD group. The median survival time (MST, year) was significantly lower in the CKD-CRC group (5.63; interquartile range [IQR], 5.26-5.91) than in the non-CKD-CRC group (8.71; IQR, 8.37-8.93). MST was significantly lower among CKD patients who received chemotherapy after adjustment by multivariate analysis (adjusted hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.37-1.49; P < 0.001]). Subgroup analysis showed that in the CKD-CRC group, MST was lower in patients who received dialysis than in those who did not, even after multivariate analysis (adjusted HR, 2.38; 95% CI, 2.20-2.58; P < 0.001). Conclusion: Prevention of CKD-to-end-stage renal disease progression should be adopted as a strategy to increase postoperative survival, along with active surveillance and cancer treatment.

Risk of gastric cancer among long-term proton pump inhibitor users: a population-based cohort study.

PURPOSE: To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk. METHODS: We searched the 2009-2019 Korean National Health Insurance Services Database for patients aged > 40 years who claimed for Helicobacter pylori eradication (HPE) during 2009-2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1 year following HPE. A propensity score (PS)-matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose-response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users. RESULTS: After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8-9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85-0.96) and 0.81 (0.76-0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06-1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25-4.60)). GC-related mortality did not differ significantly between PPI users and non-users. CONCLUSION: In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose-response relationship.

Real-World Effectiveness of Nirmatrelvir-Ritonavir and Its Acceptability in High-Risk COVID-19 Patients.

BACKGROUND: Nirmatrelvir-ritonavir is highly effective in preventing severe coronavirus disease 2019 (COVID-19) in high-risk patients with mild-to-moderate severity. However, real-world performance data are limited, and the drug is not so acceptable to the COVID-19 patients at high risk who need it in Korea. METHODS: To evaluate the effectiveness of nirmatrelvir-ritonavir, we conducted a propensity score-matched retrospective cohort study on patients with mild-to-moderate COVID-19 at high risk for a severe disease who were hospitalized at four hospitals in South Korea from February 2022 to April 2022. A total of 236 patients in the treatment group (administered nirmatrelvir-ritonavir) and 236 in the matched control group (supportive care only) were analyzed for the primary outcome, i.e., the time to oxygen support-free survival. The secondary outcome was a composite result of disease progression. The reason for not prescribing nirmatrelvir-ritonavir to the indicated patients was also investigated. RESULTS: The treatment group showed significantly longer oxygen support-free survival than the matched control group (adjusted hazard ratio [aHR], 0.07; 95% confidence interval [CI], 0.01-0.31; P < 0.001). Multivariate Cox regression analysis showed that age (aHR, 1.03; 95% CI, 1.00-1.07), National Early Warning Score-2 at admission (aHR, 1.36; 95% CI, 1.08-1.71), nirmatrelvir-ritonavir treatment, female sex (aHR, 0.37; 95% CI, 0.15-0.88), and time from symptom onset to admission (aHR, 0.67; 95% CI, 0.48-0.95) were significantly associated with oxygen therapy. However, none of the factors were related to the composite outcome. In the unmatched control group, 19.9% of 376 patients had documented explanations for nirmatrelvir-ritonavir non-prescription, and 44.0% of these were due to contraindication criteria. In the treatment group, 10.9% of patients discontinued the medication primarily because of adverse events (71.4%), with gastrointestinal symptoms being the most common (50.0%). CONCLUSION: Nirmatrelvir-ritonavir treatment significantly reduced oxygen therapy requirements in high-risk patients with COVID-19 during the omicron variant surge in South Korea. Physicians are encouraged to consider the active use of nirmatrelvir-ritonavir and to be watchful for gastrointestinal symptoms during medication.

Peripheral Nerve Blockade in Total Hip Arthroplasty: A Retrospective Study with Propensity Score Matching.

The effect of peripheral nerve block (PNB) according to leg lengthening following total hip arthroplasty (THA) has not been studied yet. The purpose of this study was to investigate the effect of PNB according to the change in leg length after THA. From January 2016 to August 2021, 353 patients who underwent unilateral THA for osteonecrosis of the femoral head or osteoarthritis of the hip joint were retrospectively reviewed. The patients were divided into two groups for comparison: 217 patients who controlled postoperative pain using only intravenous venous patient-controlled analgesia (IV PCA) (PCA group) and 136 patients who controlled postoperative pain using PNB and IV PCA (PCA + PNB group). We further divided the patients into two groups (leg lengthening after surgery < 10 mm and >10 mm) and compared them. After propensity score matching, the PCA and PCA + PNB groups, with 134 patients each, were compared and analyzed. The pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 6, 24, and 48 h (p = 0.0001, 0.0009, and <0.0001, respectively). In the subgroup analysis, for patients whose limb lengthening was less than 10 mm after THA, the pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 24 and 48 h (p = 0.0165 and 0.0015, respectively). However, in patients whose limb lengthening was more than 10 mm after THA, there was no significant difference between the pain intensity at activity and rest in the two groups at postoperative 6, 24, and 48 h (p > 0.05). PNB did not show superiority in terms of pain reduction in patients whose limb lengthening was more than 10 mm after THA. Further investigations on methods for reducing pain in patients whose leg length is increased by more than 10 mm are needed.

Reactive Oxygen Species and H. pylori Infection: A Comprehensive Review of Their Roles in Gastric Cancer Development.

Gastric cancer (GC) is the fifth most common cancer worldwide and makes up a significant component of the global cancer burden. Helicobacter pylori (H. pylori) is the most influential risk factor for GC, with the International Agency for Research on Cancer classifying it as a Class I carcinogen for GC. H. pylori has been shown to persist in stomach acid for decades, causing damage to the stomach's mucosal lining, altering gastric hormone release patterns, and potentially altering gastric function. Epidemiological studies have shown that eliminating H. pylori reduces metachronous cancer. Evidence shows that various molecular alterations are present in gastric cancer and precancerous lesions associated with an H. pylori infection. However, although H. pylori can cause oxidative stress-induced gastric cancer, with antioxidants potentially being a treatment for GC, the exact mechanism underlying GC etiology is not fully understood. This review provides an overview of recent research exploring the pathophysiology of H. pylori-induced oxidative stress that can cause cancer and the antioxidant supplements that can reduce or even eliminate GC occurrence.

Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data.

BACKGROUND: Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that primarily affects adolescents and young adults without prior liver disease or viral infections. Patients with FLC generally have non-specific symptoms, are often diagnosed at a later stage, and experience a higher frequency of metastases compared to patients with other liver cancers. A fusion transcript of DNAJB1 and PRKACA, which can lead to increased activity of PKA and cellular proliferation, has been identified in all FLC patients, but the exact mechanism through which FLC develops remains unclear. In this study, we investigated common lncRNA profiles in various FLC samples using bioinformatics analyses. METHODS: We analyzed differentially expressed (DE) lncRNAs from three RNA sequencing datasets. Using lncRNAs and DE mRNAs, we predicted potential lncRNA target genes and performed Gene Ontology (GO) and KEGG analyses with the DE lncRNA target genes. Moreover, we screened for small-molecule compounds that could act as therapeutic targets for FLC. RESULTS: We identified 308 DE lncRNAs from the RNA sequencing datasets. In addition, we performed a trans-target prediction analysis and identified 454 co-expressed pairs in FLC. The GO analysis showed that the lncRNA-related up-regulated mRNAs were enriched in the regulation of protein kinase C signaling and cAMP catabolic processes, while lncRNA-related down-regulated mRNAs were enriched in steroid, retinol, cholesterol, and xenobiotic metabolic processes. The analysis of small-molecule compounds for FLC treatment identified vitexin, chlorthalidone, triamterene, and amiloride, among other compounds. CONCLUSIONS: We identified potential therapeutic targets for FLC, including lncRNA target genes as well as small-molecule compounds that could potentially be used as treatments. Our findings could contribute to furthering our understanding of FLC and providing potential avenues for diagnosis and treatment.

Proton pump inhibitor use and the risk of metachronous gastric cancer after H. pylori eradication in patients who underwent endoscopic resection for gastric neoplasms: A population-based cohort study.

BACKGROUND: The association between proton pump inhibitors (PPI) use and gastric cancer remains controversial. AIMS: To investigate the impact of long-term PPI use on metachronous gastric cancer after Helicobacter pylori eradication in high-risk patients who underwent endoscopic resection of gastric neoplasms. METHODS: Using the Korean National Health Insurance Services database, we identified 1836 PPI users and 12,218 non-users among patients who received H. pylori eradication therapy after endoscopic resection for gastric neoplasms between 2009 and 2014. We then compared the incidence of metachronous gastric cancer between the PPI user and non-user groups. We conducted sensitivity analysis using various time lags and propensity score-matched analysis to ensure the robustness of the results. RESULTS: After a median follow-up of 7.3 years, the incidence of metachronous gastric cancer was significantly higher in the PPI user group than in the non-user group, with a crude hazard ratio of 6.20 (95% confidence interval, 5.78-6.65). After adjustment, PPI use was associated with the development of metachronous gastric cancer, with an adjusted hazard ratio of 5.51 (95% confidence interval, 5.12-5.92). The PPI user group was categorised into three subgroups according to the cumulative PPI dose; the increased risk of metachronous gastric cancer remained significant regardless of the PPI dose. Moreover, these results remained robust after applying various time lags and propensity score-matched analyses. CONCLUSIONS: Long-term PPI use is associated with an increased risk of metachronous gastric cancer in patients who undergo H. pylori eradication therapy after endoscopic resection of gastric neoplasms.

Human primary myoblasts derived from paraspinal muscle reflect donor age as an experimental model of sarcopenia.

BACKGROUND: Low back pain is a general phenomenon of aging, and surgery is an unavoidable choice to relieve severe back pain. The discarded surgical site during surgery is of high value for muscle and muscle-related research. This study investigated the age-dependent properties of patients' paraspinal muscles at the cellular level. METHODS: To define an association of paraspinal muscle degeneration with sarcopenia, we analyzed lumbar paraspinal muscle and myoblasts isolated from donors of various ages (25-77 years). Preoperative evaluations were performed by bioimpedance analysis using the InBody 720, magnetic resonance (MR) imaging of the lumbar spine, and lumbar extension strength using a lumbar extension dynamometer. In addition, the growth and differentiation capacity of myoblasts obtained from the donor was determined using proliferation assay and western blotting. RESULTS: The cross-sectional area of the lumbar paraspinal muscle decreased with age and was also correlated with the appendicular skeletal muscle index (ASM/height2). Human primary myoblasts isolated from paraspinal muscle preserved their proliferative capacity in vitro, which tended to decrease with donor age. The age-dependent decline in myoblast proliferation was correlated with levels of cell cycle inhibitory proteins (p16INK4a, p21CIP1, and p27KIP1) associated with cellular senescence. Primary myoblasts isolated from younger donors differentiated into multinucleate myotubes earlier and at a higher rate than those from older donors in vitro. Age-dependent decline in myogenic potential of the isolated primary myoblasts was likely correlated with the inactivation of myogenic transcription factors such as MyoD, myogenin, and MEF2c. CONCLUSIONS: Myoblasts isolated from human paraspinal muscle preserve myogenic potential that correlates with donor age, providing an in vitro model of sarcopenia.

Value of cardiopulmonary exercise testing in the assessment of symptoms and quality of life in Asian patients with chronic obstructive pulmonary disease.

Background: The natural course of chronic obstructive pulmonary disease (COPD) is characterized by symptom exacerbation and quality-of-life reduction. Therefore, symptoms should be properly assessed. Some studies have demonstrated a weak correlation between cardiopulmonary exercise testing (CPET) parameters and symptoms in patients with COPD; however, data on Asian patients are lacking. We investigated the value of CPET parameters in assessing symptoms and quality of life in Asian patients with COPD. Methods: Of 681 patients who underwent CPET at Asan Medical Center between January 2020 and June 2022, we analyzed 195 patients with COPD in this retrospective study. A cycle ergometer was used for the incremental protocol. The modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT) were administered to assess the patients' symptoms. Results: The mMRC grade was related to maximal oxygen uptake (VO2 max, L/min) (Spearman's correlation coefficient ρ=-0.295, P<0.001) and physiological dead space/tidal volume ratio at peak exercise (VD/VT peak) (ρ=0.256, P<0.001). The CAT score was significantly correlated with VO2 max (L/min) (Spearman's correlation coefficient ρ=-0.297, P<0.001) and VD/VT peak (ρ=0.271, P<0.001), but had no correlation with breathing reserve (ρ=-0.122, P=0.089). The optimal cut-off values of VO2 max and VD/VT peak for predicting the onset of clinically significant dyspnea were 1.099 L/min and 0.295, respectively. Conclusions: VO2 max and VD/VT peak comprehensively reflect the symptoms and health-related quality of life of patients with COPD.

Visualizing mast cell migration to tumor sites using sodium iodide symporter of nuclear medicine reporter gene.

PURPOSE: Owing to the close relationship between mast cells and cancer progression, an imaging technique that can be applied in a clinical setting to explore the biological behavior of mast cells in the tumor microenvironment is needed. In this study, we visualized mast cell migration to lung tumor lesions in live mice using sodium iodide symporter (NIS) as a nuclear medicine reporter gene. EXPERIMENTAL DESIGN: The murine mast cell line MC-9 was infected with retrovirus including NIS, luciferase (as a surrogate marker for NIS), and Thy1.1 to generate MC-9/NFT cells. Radioiodine uptake was measured in MC-9/NFT cells, and an inhibition assay of radioiodine uptake using KCLO4 was also performed. Cell proliferation and FcεRI expression was examined in MC-9 and MC-9/NFT cells. The effect of mast cell-conditioned media (CM) on the proliferation of Lewis lung cancer (LLC) cells was examined. The migration level of MC-9/NFT cells was confirmed in the presence of serum-free media (SFM) and CM of cancer cells. After intravenous injection of MC-9/NFT cells into mice with an LLC tumor, I-124 PET/CT and biodistribution analysis was performed. RESULTS: MC-9/NFT cells exhibited higher radioiodine avidity compared to parental MC-9 cells; this increased radioiodine avidity in MC-9/NFT cells was reduced to basal level by KCLO4. Levels of FcεRI expression and cell proliferation were not different in parental MC-9 cell and MC-9/ NFT cells. The CM of MC-9/NFT cells increased cancer cell proliferation relative to that of the SFM. The migration level of MC-9/NFT cells was higher in the CM than the SFM of LLC cells. PET/CT imaging with I-124 clearly showed infiltration of reporter mast cells in lung tumor at 24 h after transfer, which was consistent with the findings of the biodistribution examination. CONCLUSION: These findings suggest that the sodium iodide symporter can serve as a reliable nuclear medicine reporter gene for non-invasively imaging the biological activity of mast cells in mice with lung tumors. Visualizing mast cells in the tumor microenvironment via a nuclear medicine reporter gene would provide valuable insights into their biological functions.

Improved gross primary production estimation in rice fields through integrated multi-scale methodologies.

Understanding productivity in agricultural ecosystems is important, as it plays a significant role in modifying regional carbon balances and capturing carbon in the form of agricultural yield. This study in particular combines information from flux determinations using the eddy covariance (EC) methodology, process-based modeling of carbon gain, remotely (satellite) sensed vegetation indices (VIs), and field surveys to assess the gross primary production (GPP) of rice, which is a primary food crop worldwide. This study relates two major variables determining GPP. The first is leaf area index (LAI) and carboxylation capacity of the rice canopy (Vcuptake), and the second being MODIS remotely sensed vegetation indices (VIs). Success in applying such derived relationships has allowed GPP to be remotely determined over the seasonal course of rice development. The relationship to VIs of both LAI and Vcuptake was analyzed first by using the regression approaches commonly applied in remote sensing studies. However, the resultant GPP estimations derived from these generic models were not consistently accurate and led to a large proportion of underestimations. The new, alternative approach developed to estimate LAI and Vcuptake uses consistent development curves for rice (i.e., relies on consistent biological regulations of plant development). The modeled GPP based on this consistent development curve for both LAI and Vcuptake agreed with R 2 from 0.76 to 0.92 (within the 95% confidence interval). The results of this study demonstrate that improved linkages between ground-based survey data, eddy flux measurements, process-based models, and remote sensing data can be constructed to estimate GPP in rice paddies. This study suggests further that the conceptual application of the consistent development curve, such as the combining of different scale measurements, has the potential to predict GPP better than the common practice of utilizing simple linear models, when seeking to estimate the critical parameters that influence carbon gain and agricultural yields.

Efficacy of lazertinib for symptomatic or asymptomatic brain metastases in treatment-naive patients with advanced EGFR mutation-positive non-small cell lung cancer: Protocol of an open-label, single-arm phase II trial.

INTRODUCTION: Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation has a higher incidence of brain metastases than wild-type EGFR mutations. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), targets both EGFR-TKI sensitizing and T790M-resistance mutations and has a higher brain penetration rate relative to first- and second-generation EGFR-TKIs. Therefore, osimertinib has become a preferred first-line therapy for advanced EGFR mutation-positive NSCLC. However, lazertinib, an emerging EGFR-TKI, has shown higher selectivity toward EGFR mutations and improved penetration of the blood-brain barrier compared to osimertinib in preclinical studies. This trial will evaluate the efficacy of lazertinib as a first-line therapy in patients with EGFR mutation-positive NSCLC who have brain metastases, with or without additional local therapy. METHODS: This is a single-center, open-label, single-arm phase II trial. A total of 75 patients with advanced EGFR mutation-positive NSCLC will be recruited. Eligible patients will receive oral lazertinib 240 mg, once daily until disease progression or intolerable toxicity is detected. Patients with moderate to severe symptoms related to brain metastasis will simultaneously receive local therapy for the brain. The primary endpoints are progression-free survival and intracranial progression-free survival. DISCUSSION: Lazertinib, in combination with local therapy for the brain, if necessary, is expected to improve the clinical benefit in advanced EGFR mutation-positive NSCLC with brain metastases, as a first-line treatment.

Comprehensive investigation of the expression profiles of common long noncoding RNAs during microglial activation.

Microglia, similar to peripheral macrophages, are the primary immune cells of the central nervous system (CNS). Microglia exist in the resting state in the healthy CNS, but can be activated and polarized into either M1 or M2 subtypes for immune defense and the maintenance of CNS homeostasis by multiple stimuli. Several long noncoding RNAs (lncRNAs) mediate human inflammatory diseases and neuropathologies by regulating their target genes. However, the function of common lncRNAs that contribute to microglial activation remains unclear. Thus, we used bioinformatic approaches to identify common lncRNAs involved in microglial activation in vitro. Our study identified several lncRNAs as common regulators of microglial activation. We identified 283 common mRNAs and 53 common lncRNAs during mouse M1 microglial activation processes, whereas 26 common mRNAs and five common lncRNAs were identified during mouse M2 microglial activation processes. A total of 648 common mRNAs and 274 common lncRNAs were identified during the activation of human M1 microglia. In addition, we identified 1,920 common co-expressed pairs in mouse M1 activation processes and 25 common co-expressed pairs in mouse M2 activation processes. Our study provides a comprehensive understanding of common lncRNA expression profiles in microglial activation processes in vitro. The list of common lncRNAs identified in this study provides novel evidence and clues regarding the molecular mechanisms underlying microglial activation.