Effects of Screen Time on Problematic Behavior in Children During the COVID-19 Pandemic in South Korea.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has led to a decrease in face-to-face classes worldwide, affecting the mental health of children and their parents. The global pandemic has increased children's overall use of electronic media. This study analyzed the effect of children's screen time on problematic behaviors during the COVID-19 pandemic. Methods: A total of 186 parents from Suwon, South Korea, were recruited to participate in an online survey. The mean age of the children was 10.14 years old, and 44.1% were females. The questionnaire included questions on children's screen time, problematic behaviors, and parental stress. Children's behavioral problems were evaluated using the Behavior Problem Index, whereas the Parental Stress Scale was used to estimate parental stress. Results: The mean smartphone usage frequency of the children was 5.35 days per week, and the mean smartphone screen time was 3.52 hours per day. Smartphone screen time (Z=4.49, p <0.001) and usage frequency (Z=2.75, p=0.006) were significantly correlated with children's behavioral problem scores. The indirect effect of parental stress on this relationship was also statistically significant (p=0.049, p=0.045, respectively). Conclusion: This study suggests that children's smartphone screen time has affected problematic behaviors during the COVID-19 pandemic. Furthermore, parental stress is related to the relationship between children's screen time and problematic behaviors.

Hyperthermia promotes M1 polarization of macrophages via exosome-mediated HSPB8 transfer in triple negative breast cancer.

PURPOSE: To investigate the mechanism underlying the modulation of M1 macrophage polarization by exosomes released from hyperthermia-treated triple-negative breast cancer (TNBC) cells. MATERIALS AND METHODS: In this study, the effects of hyperthermia on TNBC cells were examined using cell counting kit-8, apoptosis, and cell cycle assays. Transmission electron microscopy was used to identify the structure of exosomes, while bicinchoninic acid and nanoparticle tracking analysis were used to detect particle size and amounts of exosomes released after hyperthermia. The polarization of macrophages incubated with exosomes derived by hyperthermia-pretreated TNBC cells were assessed by RT-qPCR and flow cytometry analysis. Next, RNA sequencing was performed to determine the targeting molecules changed in hyperthermia-treated TNBC cells in vitro. Finally, the mechanism underlying the modulation of macrophage polarization by exosomes derived from hyperthermia-treated TNBC cells was examined by using RT-qPCR, immunofluorescence and flow cytometry analysis. RESULTS: Hyperthermia markedly reduced cell viability in TNBC cells and promoted the secretion of TNBC cell-derived exosomes. The hub genes of hyperthermia-treated TNBC cells were significantly correlated with macrophage infiltration. Additionally, hyperthermia-treated TNBC cell-derived exosomes promoted M1 macrophage polarization. Furthermore, the expression levels of heat shock proteins, including HSPA1A, HSPA1B, HSPA6, and HSPB8, were significantly upregulated upon hyperthermia treatment, with HSPB8 exhibiting the highest upregulation. Moreover, hyperthermia can induce M1 macrophage polarization by promoting exosome-mediated HSPB8 transfer. CONCLUSION: This study demonstrated a novel mechanism that hyperthermia can induce M1 polarization of macrophages via exosome-mediated HSPB8 transfer. These results will help with future development of an optimized hyperthermia treatment regime for clinical application, especially for combination treatment with immunotherapy.

Computerized Version of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS-COMP): Development and Validation of the Korean Clinician-Administered Version.

OBJECTIVE: The purpose of the present study was to develop and validate the Korean version of the clinician-administered KSADSCOMP, which is the recently updated, web-based computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia for school-age children (KSADS). METHODS: A total of 71 participants (mean age=12.04±3.86 years, female=29.57%) participated in the study. A child-adolescent psychiatrist established a diagnosis for the participant after a thorough psychiatric interview with the participant and the parent. Researchers who were blind to the diagnoses administered the clinician-administered KSADS-COMP to the parents and participants. The gold-standard diagnoses made by child-adolescent psychiatrists were compared to the current diagnoses generated by the clinician-administered KSADS-COMP. Percent agreement, Cohen's Kappa, Gwet's first-order agreement coefficient (AC1), sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Gwet's AC1, our preferred measure of agreement, showed excellent range between 0.78 and 1. Sensitivity, specificity, positive predicted value and negative predictive value also showed high scores. CONCLUSION: The current study demonstrated excellent criterion validity of the Korean version of the clinician-administered KSADSCOMP, though the small sample size could be a limitation. The current study was the first study to examine the criterion validity of the KSADS-COMP. Due to its readily usable format and efficient and accurate diagnostic process, widely-use of KSADS-COMP is expected.

Safety outcomes of selective serotonin reuptake inhibitors in adolescent attention-deficit/hyperactivity disorder with comorbid depression: the ASSURE study.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation. METHODS: We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings. RESULTS: The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25-0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups. CONCLUSION: The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.

Validation of the Korean self-administered computerized versions of the kiddie schedule for affective disorders and schizophrenia for school-age children (KSADS-COMP).

The purpose of the present study was to examine the validity of the Korean version of the parent and youth self-administered versions of the KSADS-COMP (The Kiddie Schedule for Affective Disorders and Schizophrenia for school-age children). To assess the criterion validity of the KSADS-COMP, diagnoses made by the selfadministered KSADS-COMP were compared to the gold-standard diagnoses made by the child-adolescent psychiatrists in 41 participants (mean age=14.93 ± 2.16 years, female=41.46 %). Gwet's first order agreement coefficient (AC1) concordance ratings showed moderate to good range. The present study shows promising validity of the Korean self-administered versions of the KSADS-COMP in Korean youths.

Anti-Inflammatory, Antioxidative, and Nitric Oxide-Scavenging Activities of a Quercetin Nanosuspension with Polyethylene Glycol in LPS-Induced RAW 264.7 Macrophages.

Quercetin (Qu) is a dietary antioxidant and a member of flavonoids in the plant polyphenol family. Qu has a high ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) molecules; hence, exhibiting beneficial effects in preventing obesity, diabetes, cancer, cardiovascular diseases, and inflammation. However, quercetin has low bioavailability due to poor water solubility, low absorption, and rapid excretion from the body. To address these issues, the usage of Qu nanosuspensions can improve physical stability, solubility, and pharmacokinetics. Therefore, we developed a Qu and polyethylene glycol nanosuspension (Qu-PEG NS) and confirmed its interaction by Fourier transform infrared analysis. Qu-PEG NS did not show cytotoxicity to HaCaT and RAW 264.7 cells. Furthermore, Qu-PEG NS effectively reduced the nitrogen oxide (NO) production in lipopolysaccharide (LPS)-induced inflammatory RAW 264.7 cells. Additionally, Qu-PEG NS effectively lowered the levels of COX-2, NF-κB p65, and IL-1ß in the LPS-induced inflammatory RAW 264.7 cells. Specifically, Qu-PEG NS exhibited anti-inflammatory properties by scavenging the ROS and RNS and mediated the inhibition of NF-κB signaling pathways. In addition, Qu-PEG NS had a high antioxidant effect and antibacterial activity against Escherichia coli and Bacillus cereus. Therefore, the developed novel nanosuspension showed comparable antioxidant, anti-inflammatory, and antibacterial functions and may also improve solubility and physical stability compared to raw quercetin.

Long-term methylphenidate use for children and adolescents with attention deficit hyperactivity disorder and risk for depression, conduct disorder, and psychotic disorder: a nationwide longitudinal cohort study in South Korea.

BACKGROUND: Methylphenidate (MPH) is the most frequently prescribed medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, the safety of its long-term use remain unclear. In particular, real-world evidence of long-term MPH treatment regarding the risk of depression, conduct disorders, and psychotic disorders in children and adolescents is needed. This study aimed to compare the risks of depression, conduct disorder, and psychotic disorder between long- and short-term MPH treatments in children and adolescents. METHODS: This population-based cohort study used a nationwide claims database of all patients with ADHD in South Korea. Patients aged less than 18 years who were prescribed MPH were included in the study. Long- and short-term MPH were defined as > 1 year, and < 1 year, respectively. Overall, the risk of developing depressive disorder, conduct disorder and oppositional defiant disorder (ODD), and psychotic disorder were investigated. A 1:2 propensity score matching was used to balance the cohorts, and the Cox proportional hazards model was used to evaluate the safety of MPH. RESULTS: We identified 1309 long-term and 2199 short-term MPH users. Long-term MPH use was associated with a significantly lower risk of depressive (hazard ratio [HR], 0.70 [95% confidence interval [CI] 0.55-0.88]) and conduct disorders and ODD (HR, 0.52 [95% CI 0.38-0.73]) than short-term MPH use. Psychotic disorder was not significantly associated with long-term MPH use (hazard ratio [HR], 0.83 [95% confidence interval [CI] 0.52-1.32]). CONCLUSIONS: Our findings suggest that long-term MPH use may be associated with a decreased risk of depression, conduct disorders and ODD. Moreover, the long-term use of MPH does not increase the risk of psychotic disorders. Long-term MPH administration may be considered as a favourable treatment strategy for children and adolescents with ADHD regarding depressive, conduct, and psychotic disorders.

Expression profile and prognostic values of SMC family members in HCC.

OBJECTIVE: The structural maintenance of chromosome (SMC) gene family, including 6 proteins, is involved in a wide range of biological functions in different human cancers. Nevertheless, there is little research on the expression patterns, potential functions and prognostic value of SMC genes in hepatocellular carcinoma (HCC). Based on publicly available databases and integrative bioinformatics analysis, we tried to determine the value of SMC gene expression in predicting the risk of developing HCC. METHODS: The expression and copy number variations data of SMC family members were obtained from TCGA (The Cancer Genome Atlas). We identified the prognostic values of SMC family members and their clinical features. GSEA (Gene Set Enrichment Analysis) was conducted to detect the mechanism underlying the involvement of SMC family members in liver cancer. We used Tumor Immune Estimation Resource database to explore the associations between TIICs (Tumor Immune Infiltrating Cells) and the SMC family members. RESULTS: Our analysis proved that downregulation of SMC family members was common modification in HCC patients. In HCC, the expression of SMC1A, SMC2, SMC3, SMC4, SMC6 were upregulated. Upregulation of SMC2, SMC3, and SMC4, along with the clinical stage of HCC, were associated with a poor prognosis according to the results of univariate and multivariate Cox proportional hazards regression analysis. SMC2, SMC3, and SMC4 are also related to tumor purity and immune infiltration levels of HCC. The GSEA results proved that SMC family members take part in numerous biological processes underlying tumorigenesis. CONCLUSION: In this study, we comprehensively analyzed the expression of SMC family members in patients with HCC. This can provide insights for further investigation of the SMC members as potential therapeutic targets in HCC and suggest that the use of SMC inhibitor targeting SMC2, SMC3, and SMC4 can be a practical strategy for the therapy of HCC.

Identification of TIMP2 as a Prognostic Biomarker and Its Correlation with Tumor Immune Microenvironment: A Comprehensive Pan-Cancer Analysis.

Background: Tissue inhibitor of metalloproteinase-2 (TIMP2), an endogenous inhibitor of matrix metalloproteinases, has been disclosed to participate in the development and carcinogenesis of multiple malignancies. However, the prognosis of TIMP2 in different cancers and its correlation with tumor microenvironment and immunity have not been clarified. Methods: In this study, we conducted a comprehensive bioinformatics analysis to evaluate the prognostic and therapeutic value of TIMP2 in cancer patients by utilizing a series of databases, including Oncomine, GEPIA, cBioPortal, GeneMANIA, Metascape, and Sangerbox online tool. The expression of TIMP2 in different cancers was analyzed by Oncomine, TCGA, and GTEx databases, and mutation status of TIMP2 in cancers was then verified using the cBioPortal database. The protein-protein interaction (PPI) network of the TIMP family was exhibited by GeneMANIA. The prognosis of TIMP2 in cancers was performed though the GEPIA database and Cox regression. Additionally, the correlations between TIMP2 expression and immunity (immune cells, gene markers of immune cells, TMB, MSI, and neoantigen) were explored using Sangerbox online tool. Results: The transcriptional level of TIMP2 in most cancerous tissues was significantly elevated. Survival analysis revealed that an elevated expression of TIMP2 is associated with unfavorable survival outcome in multiple cancers. Enrichment analysis demonstrated the possible mechanisms of TIMPs and their associated genes mainly involved in pathways including extracellular matrix (ECM) regulators, degradation of ECM and ECM disassembly, and several other signaling pathways. Conclusions: Our findings systematically dissected that TIMP2 is a potential prognostic maker in various cancers and use the inhibitor of TIMP2, which may be an effective strategy for cancer therapy to improve the poor cancer survival and prognostic accuracy, but concrete mechanisms need to be validated by subsequent experiments.

Lower-Income Predicts Increased Smartphone Use and Problematic Behaviors Among Schoolchildren During COVID-19 Related School Modification: A Longitudinal Study.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) has continued for a couple of years, the long-term effects of the pandemic and the subsequent school curriculum modification on the mental health of children and parents need to be investigated. To clarify the changes that can occur during one school year and to predict the risk factors for vulnerable groups, this study identified parameters relative to children's screen time, their problematic behavior, and parental depression. METHODS: A total of 186 participants were analyzed who were parents of elementary schoolchildren in South Korea. These parents were required to complete a web-based questionnaire twice. The questionnaires were conducted in June 2020 and September 2021. Participants' general demographics including family income, children's screen time, sleep patterns, problematic behavior, and parental depression were assessed via the parental questionnaire that included various measurement tools. RESULTS: Children's body mass index (BMI) increased significantly in 2021 (18.94 ± 3.75 vs. 18.14 ± 3.30, P < 0.001). Smartphone frequency of use per week (5.35 vs. 4.54, P < 0.001) and screen time per day (3.52 vs. 3.16, P < 0.001) significantly increased during the period of the COVID-19 pandemic. The television screen time (2.88 vs. 3.26, P < 0.001), frequency of viewing (3.77 vs. 4.77, P < 0.001), and children's problematic behaviors significantly decreased (9.15 vs. 11.85, P < 0.001). A lower income household was a key predictor of increased smartphone frequency (B = 1.840, 95% confidence interval [CI], 0.923-2.757, P < 0.001) and smartphone screen time (B = 1.992, 95% CI, 1.458-2.525, P < 0.001). The results showed that the lower income household (B = 5.624, 95% CI, 2.927-8.320, P < 0.001) and a child's psychiatric treatment history (B = 7.579, 95% CI, 5.666-9.492, P < 0.001) was the most significant predictor of problematic behaviors of children and parental depression (B = 3.476, 95% CI, 1.628-5.325, P < 0.001; B = 3.138, 95% CI, 1.827-4.450, P < 0.001). CONCLUSION: This study suggested that children's smartphone screen time and BMI increased during COVID-19 because of the school curriculum modification following school closures in South Korea. The increased children's problematic behaviors and parental depression were predicted by lower-income households and the previous psychiatric history of children. These results indicate that multiple social support systems to the vulnerable group are needed during the ongoing pandemic and that a modified school setting is required.

Exosomal microRNAs shuttling between tumor cells and macrophages: cellular interactions and novel therapeutic strategies.

Extracellular vesicles secreted by tumor microenvironment (TME) cells are vital players in tumor progression through transferring nucleic acids and proteins. Macrophages are the main immune cells in TME and tumor associated macrophages (TAM) express M2 phenotype, which induce tumor proliferation, angiogenesis, invasion, metastasis and immune elimination, resulting in the subsequent evolution of malignancies. There are a high number of studies confirmed that tumor cells and TAM interact with each other through extracellular vesicles in various cancers, like pancreatic ductal adenocarcinoma, gastric cancer, breast cancer, ovarian cancer, colon cancer, glioblastoma, hepatocellular cancer, and lung cancer. Herein, this review summarizes the current knowledge on mechanisms of communications between tumor cells and TAM via extracellular vesicles, mainly about microRNAs, and targeting these events might represent a novel approach in the clinical implications of this knowledge into successful anti-cancer strategies.

Bioinformatics analysis revealing prognostic significance of TIMP2 gene in breast cancer.

ABSTRACT: Tissue inhibitor of metalloproteinases 2 (TIMP2) is a member of the TIMP gene family. Accumulated evidence indicates that TIMP2 plays a significant role in various tumor processes including cell growth, apoptosis, invasion, and metastasis. However, the expression patterns and exact roles of TIMP2 had not been elucidated in breast cancer. In our research, we evaluated the expression and prognostic value of TIMP2 in breast cancer through analyzing various databases including Oncomine, bc-GenExMiner, PrognoScan, UCSC Xena, Kaplan-Meier Plotter, and PPI network. The results showed that TIMP2 was down-regulated in various breast cancer subtypes. Additionally, TIMP2 was significantly associated with age, estrogen receptor status, basal-like group, triple-negative breast cancer, PAM50 subtypes, and RSSPC subtypes. Also, the expression of TIMP2 was related to overall survival with different clinical characteristics. We analyzed the co-expressed genes with TIMP2 and interaction information with other proteins. These results disclosed that TIMP2 might serve as a potential target and prognostic biomarker in breast cancer. However, additional research is required to demonstrate our findings and motivate the clinical importance of TIMP2 in breast cancer.

Autophagy Modulation and Synergistic Therapy to Combat Multidrug Resistance Breast Cancer Using Hybrid Cell Membrane Nanoparticles.

The development of multidrug resistance (MDR) is a commonly observed phenomenon in many cancer types. It contributed significantly to the poor outcome of many currently available chemotherapies. Considering autophagy as one of the most important physiological process in cancer progression, we thereby proposed an anti-autophagy siRNA and doxorubicin (Dox) co-delivery system (MC/D-siR) to combat MDR breast cancer using sequential construction. Our results demonstrated the potential of MC/D-siR to effectively transfect the loaded siRNA to result in significant downregulation of intracellular autophagy level in MCF-7/Adr (Dox resistance MCF-7 cell line) cells, which in turn cut off the ATP supply and to reverse the MDR and potentiated accumulated drug retention in cells. As a result, MC/D-siR showed much elevated anticancer benefits than single loaded platforms (MC/Dox or MC/siRNA), indicating the ability for effective MDR cancer treatment through the combination of autophagy regulation and chemotherapy.

Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes.

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

Parental Mental Health and Children's Behaviors and Media Usage during COVID-19-Related School Closures.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is different from previous disasters in that it continues to the present and has affected all aspects of family life. During epidemics, psychosocial support is not less important than infection control. During COVID-19-related school closures, prolonged partial closures of schools could have detrimental social and health consequences for children and may increase the burden on the family. Based on a community sample in Korea, this study identified parental concerns, children's media usage, other various factors and examined whether parental stress level or depression were positively associated with problem behaviors, media exposure, and sleep problems of the primary school children during school closure under COVID-19. METHODS: Participants were 217 parents residing in Suwon, South Korea, who had primary school children and responded to a web-based questionnaire on parental concerns from school closure under COVID-19, subjective stress, depression, whether having received mental health services, and family characteristics; children's sleep patterns, problem behaviors, media usage during the online-only class period, and changes in activity level following the pandemic. RESULTS: During school closure, children gained body weight, spent less time in physical activities and more in media usage. Besides online learning content (97.2%), YouTube was highly used content (87.6%), and games followed (78.3%). Parental subjective stress index was highly associated with parental depression (Pearson correlation 0.439, P < 0.001), children's sleep problems (0.283, P < 0.001), tablet time (0.171, P = 0.012) and behavior problems (0.413, P < 0.001). Parental depression was associated with children's sleep problems (0.355, P < 0.001), TV time (0.153, P = 0.024), tablet time (0.159, P = 0.019), and behavior problems (0.524, P < 0.001). Parents who previously received mental services seemed to be more concerned about the problems their children already have getting worse because of COVID-19 than the disease itself. Children's sleep problem was associated with tablet (0.172, P = 0.011) and smartphone time (0.298, P < 0.001), but not its frequency. CONCLUSION: During COVID-19-related school closures, many parents and children had various difficulties relating to mental health. Ongoing monitoring of mental health of high-risk groups and multiple support systems may need to be expanded to cover those parents having difficulty in caring for their children.

Systematic Characterization of Expression Profiles and Prognostic Values of the Eight Subunits of the Chaperonin TRiC in Breast Cancer.

BACKGROUND: Chaperonin-containing TCP-1 (TRiC or CCT) was demonstrated to be involved in oncogenesis of cancers carcinogenesis and development of various malignancies. Increasing experimental evidence indicated that dysregulation of TRiC was implicated in the tumor progression of breast cancer (BCa). However, few definitive studies have addressed the diverse expression patterns and prognostic values of eight TRiC subunits. Thus, we aimed to investigate the clinical significance of TRiC subunit expression and prognostic values for their possible implications in diagnosis and treatment of BCa. METHODS: Based on updated public resources and comprehensive bioinformatics analysis, we used some online databases (e.g., UALCAN, GEPIA, cBioPortal, TIMER, BC-GenExMiner, metascape, and GeneMANIA) to comprehensively explore the expression levels and the prognostic effects of eight TRiC subunits in patients with BCa. RESULTS: The transcriptional levels of most subunits of the Chaperonin TRiC (CCT2, CCT3, CCT4, CCT5, CCT6A, and CCT7) were significantly elevated compared with normal breast tissues, whereas TCP1, CCT4, and CCT6B were lower in BCa tissues than in normal tissues. Besides, copy-number alterations (CNA) of eight TRiC subunits positively regulated their mRNA expressions. Furthermore, high mRNA expression of TCP1/CCT2/CCT4/CCT5/CCT6A/CCT7/CCT8 was significantly associated with poor overall survival (OS) in BCa patients. The eight subunits of the chaperonin TRiC was related to tumor purity and immune infiltration levels of BCa. Co-expression analysis showed CCT6B was negatively associated with other subunits of TRiC and other subunits of TRiC were positively correlated with each other. Additionally, TRiC and their interactive proteins were correlated with positive regulation of biological process, localization, and biological regulation. CONCLUSION: This study systematically illustrated the expression profiles and distinct prognostic values of chaperonin TRiC in BCa, providing insights for further investigation of subunits of the chaperonin TRiC as novel therapeutic targets and potential prognostic biomarkers in BCa.

Tumor-derived exosomal circPSMA1 facilitates the tumorigenesis, metastasis, and migration in triple-negative breast cancer (TNBC) through miR-637/Akt1/ß-catenin (cyclin D1) axis.

Circular RNAs (circRNAs) are increasingly gaining importance and attention due to their diverse potential functions and their value as diagnostic biomarkers (disease specific). This study aims to explore the novel mechanisms by which exosome-contained circRNAs promote tumor development and metastasis in TNBC. We identified increased circRNA circPSMA1 in TNBC cells, their exosomes, and serum exosomes samples from TNBC patients. The overexpression of circPSMA1 promoted TNBC cell proliferation, migration, and metastasis both in vitro and in vivo. Moreover, we investigated the tumor-infiltrating immune cells (TICs) or stromal components in immune microenvironment (IME), and identified the significant differences in the immune cells between TNBC and non-TNBC samples. Mechanistically, circPSMA1 acted as a "miRNAs sponge" to absorb miR-637; miR-637 inhibited TNBC cell migration and metastasis by directly targeted Akt1, which recognized as a key immune-related gene and affected downstream genes ß-catenin and cyclin D1. Subsequent co-culture experiments also demonstrated that exosomes from TNBC carrying large amounts of circPSMA1 could transmit migration and proliferation capacity to recipient cells. Kaplan-Meier plots showed that high expression of Akt1 and low expression of mir-637 are highly correlated with poor prognosis in patients with lymph node metastasis of TNBC. Collectively, all these results reveal that circPSMA1 functions as a tumor promoter through the circPSMA1/miR-637/Akt1-ß-catenin (cyclin D1) regulatory axis, which can facilitate the tumorigenesis, metastasis, and immunosuppression of TNBC. Our research proposes a fresh perspective on novel potential biomarkers and immune treatment strategies for TNBC.

Association of decreased grip strength with lower urinary tract symptoms in women: a cross-sectional study from Korea.

BACKGROUND: Lower urinary tract symptoms (LUTS) including frequency, nocturia, urgency, and incontinence, are common in women and cause significant discomfort in daily life. However, diagnosis and treatment of LUTS are often delayed because many patients with such symptoms do not complain to the physician of discomfort and do not seek medical attention. LUTS are known to be associated with muscle weakness. We investigated the association between grip strength and LUTS in women of different ages. METHODS: This study included 4225 women (mean age 48.6 years) who underwent self-referred health screening between April 2015 and December 2019. LUTS were evaluated using a self-reported questionnaire, and the overactive bladder symptom score was used to screen for an overactive bladder. Low muscle strength was defined as a hand grip strength of < 18 kg (decreased grip strength). RESULTS: We observed decreased grip strength in 13.7% (n = 580) of the participants. Nocturia, urgency, incontinence, and overactive bladder were more common in women with decreased grip strength than in women with normal grip strength. After adjusting for age, comorbidities (hypertension, diabetes, hyperlipidemia), smoking status, alcohol consumption, regular exercise, and stress, nocturia (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01-1.52), urinary incontinence (OR 1.32, 95% CI 1.01-1.72), and an overactive bladder (OR 1.75, 95% CI 1.35-2.27) were significantly associated with decreased grip strength. CONCLUSIONS: The findings suggest that LUTS, especially nocturia, incontinence, and an overactive bladder are associated with decreased grip strength in women. Therefore, physicians should be aware that patients may not seek help, even if they are uncomfortable, and it is important to obtain a detailed medical history and perform additional tests, even in the absence of complaints, in patients with low grip strength, who are at high risk of LUTS.

Breast metastasis from rectal carcinoma: A case report and review of the literature.

BACKGROUND: Metastasis from extramammary primary tumor to breast is extremely rare. CASE SUMMARY: A 59-year-old woman with 1-year history of rectal cancer presented with asymptomatic breast mass. At 16 months after the diagnosis of rectal mucinous adenocarcinoma, a breast mass was confirmed by ultrasonography and identified by pathology and immunohistochemistry as a metastasis from the rectal cancer. Treatments included chemotherapy (6 cycles: 300 mg irinotecan on day 1, 4.5 mg raltitrexed on day 2, 450 mg bevacizumab on day 3), radiotherapy, and surgical resection. Two years of follow-up examinations (6-months intervals) showed no evidence of recurrence or novel distant metastasis. CONCLUSION: Breast metastasis from rectal carcinoma is a rare secondary malignancy. Final diagnosis can be established by histopathology and immunohistochemistry.