Predictive model for contralateral inguinal hernia repair within three years of primary repair: a nationwide population-based cohort study.

BACKGROUND: Limited reports have discussed the risk factors for contralateral inguinal hernia (CIH) repair. We generated a risk factor scoring system to predict CIH within 3 years after unilateral inguinal hernia repair. METHODS: We extracted the admission data of patients aged ≥ 18 years who underwent primary unilateral inguinal hernia repair without any other operation from the National Health Insurance Research Database. Patients were randomly divided into 80% and 20% validation cohorts. Multivariate analysis with a logistic regression model was used to generate the scoring system, which was used in the validation group. RESULTS: Overall, 170,492 adult men were included, with a median follow-up of 87 months. The scoring system ranged from 0-5 points, composited with age (< 45 years, 0 points; 45-65 years, 2 points; 65-80 years, 3 points; > 80 years, 2 points) and two comorbidities (cirrhosis and prostate disease: 1 point each). The areas under receiver operating characteristic (ROC) curves were 0.606 and 0.551 for the derivation and validation groups, respectively. The rates and adjusted odds ratios (OR) of CIH repair in the derivation group were 3.0% at 0-2 points, 5.5% (1.854, p < 0.001) at 3, 6.7% (2.279, p < 0.001) at 4, and 6.9% (2.348, p < 0.001) at 5, with similar results in the validation group [2.3% at 0-2 points, 3.8% (1.668, p < 0.001) at 3, 5.4% (2.386, p < 0.001) at 4, and 6.8% (3.033, p < 0.001) at 5]. CONCLUSIONS: The CIH scoring system effectively predicted CIH repair within three years of primary unilateral inguinal hernia repair. Surgeons could perform laparoscopic surgery with CIH scores > 2 points which enables easier contralateral exploration and repair during the same surgery, without additional incisions, to minimize the need for future surgeries. However, further prospective validation of this scoring system is required.

Assessing risk of recurrent small bowel obstruction after non-operative management in patients with history of intra-abdominal surgery: a population-based comprehensive analysis in Taiwan.

BACKGROUND: Despite a significant 30% ten-year readmission rate for SBO patients, investigations into recurrent risk factors after non-operative management are scarce. The study aims to generate a risk factor scoring system, the 'Small Bowel Obstruction Recurrence Score' (SBORS), predicting 6-month recurrence of small bowel obstruction (SBO) after successful non-surgical management in patients who have history of intra-abdominal surgery. METHODS: We analyzed data from patients aged ≥ 18 with a history of intra-abdominal surgery and diagnosed with SBO (ICD-9 code: 560, 568) and were successful treated non-surgically between 2004 and 2008. Participants were divided into model-derivation (80%) and validation (20%) group. RESULTS: We analyzed 23,901 patients and developed the SBORS based on factors including the length of hospital stay > 4 days, previous operations > once, hemiplegia, extra-abdominal and intra-abdominal malignancy, esophagogastric surgery and intestino-colonic surgery. Scores > 2 indicated higher rates and risks of recurrence within 6 months (12.96% vs. 7.27%, OR 1.898, p < 0.001 in model-derivation group, 12.60% vs. 7.05%, OR 1.901, p < 0.001 in validation group) with a significantly increased risk of mortality and operative events for recurrent episodes. The SBORS model demonstrated good calibration and acceptable discrimination, with an area under curve values of 0.607 and 0.599 for the score generation and validation group, respectively. CONCLUSIONS: We established the effective 'SBORS' to predict 6-month SBO recurrence risk in patients who have history of intra-abdominal surgery and have been successfully managed non-surgically for the initial obstruction event. Those with scores > 2 face higher recurrence rates and operative risks after successful non-surgical management.

Association of sodium-glucose cotransporter 2 inhibitors with the incidence of corneal diseases in type 2 diabetes mellitus.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors revealed the protective function on various systemic diseases. This study aimed to determine whether the usage of SGLT2 inhibitors associates with incidences of superficial keratopathy and infectious keratitis in type 2 diabetes mellitus (T2DM) patients. A retrospective cohort study with the usage of National Health Insurance Research Database of Taiwan was conducted. The T2DM patients were divided into the SGLT2 inhibitors and control groups according to the usage of SGLT2 inhibitors or not. The major outcomes were defined as the occurrence of superficial keratopathy and infectious keratitis. There were 766 and 1037 episodes of superficial keratopathy in the SGLT2 inhibitors and control groups and SGLT2 inhibitors group showed a significantly lower incidence of superficial keratopathy than the control group (aHR: 0.721, 95% CI: 0.656-0.791, P < 0.0001). Also, there were 166 and 251 infectious keratitis events in the SGLT2 inhibitors and control groups and patients in the SGLT2 inhibitors group revealed a significantly lower infectious keratitis incidence than those in the control group (aHR: 0.654, 95% CI: 0.537-0.796, P < 0.0001). In addition, the patients that received SGLT2 inhibitors demonstrated lower cumulative incidences of both superficial keratopathy and infectious keratitis compared to the non-SGLT2 inhibitors users (both P < 0.0001). In conclusion, the usage of SGLT2 inhibitors correlates to lower incidence of superficial keratopathy and infectious keratitis in T2DM individuals, which is more significant in patients with persistent SGLT2 inhibitors application.

From Sea to Science: Coral Aquaculture for Sustainable Anticancer Drug Development.

Marine natural products offer immense potential for drug development, but the limited supply of marine organisms poses a significant challenge. Establishing aquaculture presents a sustainable solution for this challenge by facilitating the mass production of active ingredients while reducing our reliance on wild populations and harm to local environments. To fully utilize aquaculture as a source of biologically active products, a cell-free system was established to target molecular components with protein-modulating activity, including topoisomerase II, HDAC, and tubulin polymerization, using extracts from aquaculture corals. Subsequent in vitro studies were performed, including MTT assays, flow cytometry, confocal microscopy, and Western blotting, along with in vivo xenograft models, to verify the efficacy of the active extracts and further elucidate their cytotoxic mechanisms. Regulatory proteins were clarified using NGS and gene modification techniques. Molecular docking and SwissADME assays were performed to evaluate the drug-likeness and pharmacokinetic and medicinal chemistry-related properties of the small molecules. The extract from Lobophytum crassum (LCE) demonstrated potent broad-spectrum activity, exhibiting significant inhibition of tubulin polymerization, and showed low IC50 values against prostate cancer cells. Flow cytometry and Western blotting assays revealed that LCE induced apoptosis, as evidenced by the increased expression of apoptotic protein-cleaved caspase-3 and the populations of early and late apoptotic cells. In the xenograft tumor experiments, LCE significantly suppressed tumor growth and reduced the tumor volume (PC3: 43.9%; Du145: 49.2%) and weight (PC3: 48.8%; Du145: 7.8%). Additionally, LCE inhibited prostate cancer cell migration, and invasion upregulated the epithelial marker E-cadherin and suppressed EMT-related proteins. Furthermore, LCE effectively attenuated TGF-ß-induced EMT in PC3 and Du145 cells. Bioactivity-guided fractionation and SwissADME validation confirmed that LCE's main component, 13-acetoxysarcocrassolide (13-AC), holds greater potential for the development of anticancer drugs.

Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.

Test-Retest Reliability, Criterion-Related Validity, and Ecological Validity of the Test of Visual-Motor Skills, Third Edition, in Kindergarten Children With Developmental Coordination Disorder.

IMPORTANCE: Establishing empirical evidence on the psychometric properties of the Test of Visual-Motor Skills (3rd ed.; TVMS-3) is helpful for guiding its use as an assessment of visual-motor integration (VMI) skills in kindergarten children with developmental coordination disorder (DCD). OBJECTIVE: To investigate the test-retest reliability, criterion-related validity, and ecological validity of the TVMS-3 in Taiwanese kindergarten children with DCD. DESIGN: A nonexperimental, descriptive, correlational design. SETTING: A hospital in Central Taiwan. PARTICIPANTS: Fifty-seven kindergarten children with DCD were recruited in the study. OUTCOMES AND MEASURES: Intraclass correlation coefficient, percentage of minimal detectable change, and paired t test (Wilcoxon signed rank test) were used to investigate the test-retest reliability of the TVMS-3. The correlations (Pearson's r) between the TVMS-3 accuracy score and the scores of each of the four domains and the adaptive behavior composite score of the Vineland Adaptive Behavior Scales (3rd ed.; Vineland-3) were calculated, respectively, to examine criterion-related validity and ecological validity. RESULTS: The accuracy score of the TVMS-3 had excellent test-retest reliability and acceptable random measurement error. Moreover, it showed good criterion-related validity and sufficient ecological validity with the Vineland-3 in Taiwanese kindergarten children with DCD. CONCLUSIONS AND RELEVANCE: The accuracy score of the TVMS-3 is applicable to Taiwanese kindergarten children with DCD in clinical and research settings. Plain-Language Summary: The accuracy score of the Test of Visual-Motor Skills (3rd ed.; TVMS-3) is a useful assessment tool to detect deficits in visual-motor integration for Taiwanese kindergarten children with developmental coordination disorder. The TVMS-3 has excellent test-retest reliability, good criterion-related validity, and sufficient ecological validity.

Multi-omics and experimental analysis unveil theragnostic value and immunological roles of inner membrane mitochondrial protein (IMMT) in breast cancer.

BACKGROUND: The inner membrane mitochondrial protein (IMMT) is a central unit of the mitochondrial contact site and cristae organizing system (MICOS). While researchers continue to demonstrate the physiological function of IMMT in regulating mitochondrial dynamics and preserving mitochondrial structural integrity, the roles of IMMT in clinicopathology, the tumor immune microenvironment (TIME), and precision oncology in breast cancer (BC) remain unclear. METHODS: Multi-omics analysis was used here to evaluate the diagnostic and prognostic value of IMMT. Web applications aimed at analyzing the whole tumor tissue, single cells, and spatial transcriptomics were used to examine the relationship of IMMT with TIME. Gene set enrichment analysis (GSEA) was employed to determine the primary biological impact of IMMT. Experimental verification using siRNA knockdown and clinical specimens of BC patients confirmed the mechanisms behind IMMT on BC cells and the clinical significance, respectively. Potent drugs were identified by accessing the data repositories of CRISPR-based drug screenings. RESULTS: High IMMT expression served as an independent diagnostic biomarker, correlated with advanced clinical status, and indicated a poor relapse-free survival (RFS) rate for patients with BC. Although, the contents of Th1, Th2, MSC, macrophages, basophil, CD4 + T cell and B cell, and TMB levels counteracted the prognostic significance. Single-cell level and whole-tissue level analyses revealed that high IMMT was associated with an immunosuppressive TIME. GSEA identified IMMT perturbation as involved in cell cycle progression and mitochondrial antioxidant defenses. Experimental knockdown of IMMT impeded the migration and viability of BC cells, arrested the cell cycle, disturbed mitochondrial function, and increased the ROS level and lipid peroxidation. The clinical values of IMMT were amenable to ethnic Chinese BC patients, and can be extrapolated to some other cancer types. Furthermore, we discovered that pyridostatin acted as a potent drug candidate in BC cells harboring an elevated IMMT expression. CONCLUSION: This study combined a multi-omics survey with experimental verification to reveal the novel clinical significance of IMMT in BC, demonstrating its role in TIME, cancer cell growth and mitochondrial fitness, and identified pyridostatin as a promising drug candidate for the development of precision medicine.

Utilization of sodium-glucose cotransporter 2 inhibitors on dry eye disease severity in patients with type 2 diabetes mellitus.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have protective effects against various systemic diseases and neoplasms. This retrospective cohort study evaluated the severity of dry eye disease (DED) in patients with type 2 diabetes mellitus (T2DM) who were treated with SGLT2 inhibitors. Data were obtained from the National Health Insurance Research Database of Taiwan. Patients with T2DM who were treated with SGLT2 inhibitors were assigned to the SGLT2 group. Each patient in the SGLT2 group was matched to two individuals with T2DM who had not used SGLT2 inhibitors, constituting the control group. The primary outcomes were the development of DED and severe DED. A diagnosis of severe DED was indicated by the usage of cyclosporine. Cox proportional hazard regression was applied to yield adjusted hazard ratios (aHR) and 95% confidence intervals (CIs). In the SGLT2 group, 1864 new DED events and 147 severe DED events were recorded. Conversely, 4367 new DED events and 392 severe DED events were recorded in the control group. The incidence (aHR: 0.858, 95% CI: 0.811-0.908, p = 0.0010) and severity (aHR: 0.652, 95% CI: 0.481-0.777, p = 0.0006) of DED were significantly lower in the SGLT2 group than the control group after adjusting for multiple covariates. In subgroup analyses, the incidence and severity of DED were significantly lower in patients younger than 60 years old who were treated with SGLT2 inhibitors than in their older counterparts (p = 0.0008 and 0.0011, respectively). In conclusion, utilization of SGLT2 inhibitors in the T2DM population could reduce both the incidence and severity of DED.

Association of the nasopharyngeal carcinoma and the subsequent open glaucoma development: a nationwide cohort study.

This study aimed to investigate the possible association between nasopharyngeal carcinoma (NPC) and following open angle glaucoma (OAG). A retrospective research applying the National Health Insurance Research Database (NHIRD) of Taiwan was conducted with a follow up period from January 1, 2000 to December 31, 2016. There were 4184 and 16736 participants that selected and categorized into the NPC and non-NPC groups after exclusion. The major outcome of our study was the development of OAG according to diagnostic codes, exam and managements. The Cox proportional hazard regression was employed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of OAG between the two groups. In this study, a numbers of 151 and 513 OAG episodes occurred in the NPC and non-NPC groups and the NPC population showed a significantly higher incidence of OAG compared to the non-NPC population in multivariable analysis (aHR: 1.293, 95% CI: 1.077-1.551, p = 0.0057). Besides, the cumulative probability of OAG was significantly higher in the NPC group than that in the non-NPC population (p = 0.0041). About other risk factor for OAG, age older than 40 years old, diabetes mellitus and persistent steroid usage were related to OAG occurrence (all p < 0.05). In conclusion, the NPC may be an independent risk factor of following OAG development.

Effects of declines in personal mastery on self-perceived mobility, physical function, cognitive function, and depressive symptoms: a 6-year follow-up study from the Social Environment and Biomarkers of Aging Study.

OBJECTIVES: As the psychosocial competence, personal mastery helps individuals to cope with stressful life events, and this study aims to examine impacts of declines in personal mastery on healthy aging among community-dwelling middle-aged and older adults using a nationally representative cohort. METHODS: Data from 648 study participants in the Social Environment and Biomarkers of Aging Study (SEBAS) were retrieved for analysis. All participants were divided into four groups based on their baseline and changes of personal mastery (measured by the Pearlin mastery score) during the 6-year follow-up. Multivariate logistic regression models were adopted to examine associations between declines in personal mastery and indicators for healthy aging (declines in self-perceived mobility, physical function (activities of daily living (ADLs) and instrumental activities of daily living (IADLs)), cognitive function and depressive symptoms). RESULTS: After adjustments for demographics and comorbidities, those with declines in personal mastery were associated with greater risks of declines in self-perceived mobility (adjusted odds ratio (aOR) 1.50 [95% confidence interval 1.01-2.22], p < 0.05). Although the point estimate in the unadjusted models indicated similar associations between declines in personal mastery and declines in ADLs, IADLs, cognitive function or depressive symptoms, these outcomes did not reach statistical significance in the adjusted model. CONCLUSIONS: Declines in personal mastery were negatively associated with indicators related to healthy aging (particularly locomotion) in a 6-year follow-up. Further investigations are needed to explore the effects of preventing declines in personal mastery in promoting healthy aging over time.

Supervised Learning and Multi-Omics Integration Reveals Clinical Significance of Inner Membrane Mitochondrial Protein (IMMT) in Prognostic Prediction, Tumor Immune Microenvironment and Precision Medicine for Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) accounts for approximately 75% of all renal cancers. The prognosis for patients with metastatic KIRC is poor, with less than 10% surviving five years after diagnosis. Inner membrane mitochondrial protein (IMMT) plays a crucial role in shaping the inner mitochondrial membrane (IMM), regulation of metabolism and innate immunity. However, the clinical relevance of IMMT in KIRC is not yet fully understood, and its role in shaping the tumor immune microenvironment (TIME) remains unclear. This study aimed to investigate the clinical significance of IMMT in KIRC using a combination of supervised learning and multi-omics integration. The supervised learning principle was applied to analyze a TCGA dataset, which was downloaded and split into training and test datasets. The training dataset was used to train the prediction model, while the test and the entire TCGA dataset were used to evaluate its performance. Based on the risk score, the cutoff between the low and high IMMT group was set at median value. A Kaplan-Meier curve, receiver operating characteristic (ROC) curve, principal component analysis (PCA) and Spearman's correlation were conducted to evaluate the prediction ability of the model. Gene Set Enrichment Analysis (GSEA) was used to investigate the critical biological pathways. Immunogenicity, immunological landscape and single-cell analysis were performed to examine the TIME. Databases including Gene Expression Omnibus (GEO), Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) were employed for inter-database verification. Pharmacogenetic prediction was analyzed via single-guide RNA (sgRNA)-based drug sensitivity screening using Q-omics v.1.30. Low expressions of IMMT in tumor predicted dismal prognosis in KIRC patients and correlated with KIRC progression. GSEA revealed that low expressions of IMMT were implicated in mitochondrial inhibition and angiogenetic activation. In addition, low IMMT expressions had associations with reduced immunogenicity and an immunosuppressive TIME. Inter-database verification corroborated the correlation between low IMMT expressions, KIRC tumors and the immunosuppressive TIME. Pharmacogenetic prediction identified lestaurtinib as a potent drug for KIRC in the context of low IMMT expressions. This study highlights the potential of IMMT as a novel biomarker, prognostic predictor and pharmacogenetic predictor to inform the development of more personalized and effective cancer treatments. Additionally, it provides important insights into the role of IMMT in the mechanism underlying mitochondrial activity and angiogenesis development in KIRC, which suggests IMMT as a promising target for the development of new therapies.

Effects of Therapeutic Platelet-Rich Plasma on Overactive Bladder via Modulating Hyaluronan Synthesis in Ovariectomized Rat.

Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich plasma (PRP) or platelet-poor plasma (PPP) after 12 months of OVX to investigate the therapeutic effects of PRP on OHD-induced OAB. The OVX-treated rats exhibited a decrease in the expression of urothelial barrier-associated proteins, altered hyaluronic acid (hyaluronan; HA) production, and exacerbated bladder pathological damage and interstitial fibrosis through NFƘB/COX-2 signaling pathways, which may contribute to OAB. In contrast, PRP instillation for four weeks regulated the inflammatory fibrotic biosynthesis, promoted cell proliferation and matrix synthesis of stroma, enhanced mucosal regeneration, and improved urothelial mucosa to alleviate OHD-induced bladder hyperactivity. PRP could release growth factors to promote angiogenic potential for bladder repair through laminin/integrin-α6 and VEGF/VEGF receptor signaling pathways in the pathogenesis of OHD-induced OAB. Furthermore, PRP enhanced the expression of HA receptors and hyaluronan synthases (HAS), reduced hyaluronidases (HYALs), modulated the fibroblast-myofibroblast transition, and increased angiogenesis and matrix synthesis via the PI3K/AKT/m-TOR pathway, resulting in bladder remodeling and regeneration.

Novel 9-Benzylaminoacridine Derivatives as Dual Inhibitors of Phosphodiesterase 5 and Topoisomerase II for the Treatment of Colon Cancer.

It has been shown that phosphodiesterase 5 (PDE5) inhibitors have anticancer effects in a variety of malignancies in both in vivo and in vitro experiments. The role of cGMP elevation in colorectal carcinoma (CRC) has been extensively studied. Additionally, DNA topoisomerase II (Topo II) inhibition is a well-established mechanism of action that mediates the effects of several approved anticancer drugs such as doxorubicin and mitoxantrone. Herein, we present 9-benzylaminoacridine derivatives as dual inhibitors of the PDE5 and Topo II enzymes. We synthesized 31 derivatives and evaluated them against PDE5, whereby 22 compounds showed micromolar or sub-micromolar inhibition. The anticancer activity of the compounds was evaluated with the NCI 60-cell line testing. Moreover, the effects of the compounds on HCT-116 colorectal carcinoma (CRC) were extensively studied, and potent compounds against HCT-116 cells were studied for their effects on Topo II, cell cycle progression, and apoptosis. In addition to exhibiting significant growth inhibition against HCT116 cells, compounds 11, 12, and 28 also exhibited the most superior Topo II inhibitory activity and low micromolar PDE5 inhibition and affected cell cycle progression. Knowing that compounds that combat cancer through multiple mechanisms are among the best candidates for effective therapy, we believe that the current class of compounds merits further optimization and investigation to unleash their full therapeutic potential.

Diffuse lamellar keratitis as a rare complication of diamond burr superficial keratectomy for recurrent corneal erosion: a case report.

BACKGROUND: To present a case with a history of laser in situ keratomileusis (LASIK) developing diffuse lamellar keratitis (DLK) after diamond burr superficial keratectomy (DBSK) for recurrent corneal erosion (RCE). CASE PRESENTATION: A 25-year-old man presented with multiple episodes of RCE one year after femtosecond-assisted LASIK for myopia correction. Because conservative treatments failed to halt the repetitive attack of RCE, he underwent epithelial debridement and DBSK. However, severe foreign body sensation and blurred vision developed on postoperative day one. The next day, slit lamp biomicroscopy revealed DLK manifested as diffuse granular infiltrates at the flap interface. After topical corticosteroid treatment, the inflammation resolved gradually, and his vision recovered to 20/20. CONCLUSIONS: Diffuse lamellar keratitis is a rare post-LASIK complication that can be triggered by DBSK, which causes impairment of the corneal epithelial integrity and subsequent inflammation at the flap interface. For post-LASIK patients with RCE, alternative treatments, such as anterior stromal puncture, may be considered to avoid extensive disruption of corneal epithelium and DLK development depending on the size and the location of the lesions.

A Novel Role of Arrhythmia-Related Gene KCNQ1 Revealed by Multi-Omic Analysis: Theragnostic Value and Potential Mechanisms in Lung Adenocarcinoma.

The early diagnosis, prognostic prediction, and personalized therapy of lung adenocarcinoma (LUAD) remains a challenging issue. KCNQ1 (potassium voltage-gated channel subfamily Q Member 1) is implicated in long QT syndrome (LQTS) and cardiac arrhythmia, while its significance in LUAD remains unclear. In this study, we aimed to explore the significance of KCNQ1 in terms of clinical value, tumor immunity, underlying mechanisms, and a precision medicine approach by means of multi-omics analysis. The association of KCNQ1 with LUAD was first explored. Both altered variants and high expression of KCNQ1 in a TCGA-LUAD cohort indicated a favorable outcome. KCNQ1 levels had a negative correlation with tumor proliferation index Ki67 levels. siRNA-knockdown of KCNQ1 promoted the migration ability of lung cancer cells. KCNQ1 levels were decreased in LUAD tissue compared to normal tissue. A receiver operating characteristic (ROC) curve indicated good diagnostic efficiency of KCNQ1. High KCNQ1 is associated with an immunoactive profile of immune infiltration and immunomodulators and is involved in the inhibition of the cell cycle and DNA replication. Lapatinib was identified as a potent drug for LUAD in the context of low KCNQ1. This study unveiled the significance of KCNQ1 in diagnosis and prognosis and provided a corresponding precision medicine strategy for LUAD.

Heat Shock Protein 60 Restricts Release of Mitochondrial dsRNA to Suppress Hepatic Inflammation and Ameliorate Non-Alcoholic Fatty Liver Disease in Mice.

Non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, consists of fat deposited (steatosis) in the liver due to causes besides excessive alcohol use. The folding activity of heat shock protein 60 (HSP60) has been shown to protect mitochondria from proteotoxicity under various types of stress. In this study, we investigated whether HSP60 could ameliorate experimental high-fat diet (HFD)-induced obesity and hepatitis and explored the potential mechanism in mice. The results uncovered that HSP60 gain not only alleviated HFD-induced body weight gain, fat accumulation, and hepatocellular steatosis, but also glucose tolerance and insulin resistance according to intraperitoneal glucose tolerance testing and insulin tolerance testing in HSP60 transgenic (HSP60Tg) compared to wild-type (WT) mice by HFD. Furthermore, overexpression of HSP60 in the HFD group resulted in inhibited release of mitochondrial dsRNA (mt-dsRNA) compared to WT mice. In addition, overexpression of HSP60 also inhibited the activation of toll-like receptor 3 (TLR3), melanoma differentiation-associated gene 5 (MDA5), and phosphorylated-interferon regulatory factor 3 (p-IRF3), as well as inflammatory biomarkers such as mRNA of il-1ß and il-6 expression in the liver in response to HFD. The in vitro study also confirmed that the addition of HSP-60 mimics in HepG2 cells led to upregulated expression level of HSP60 and restricted release of mt-dsRNA, as well as downregulated expression levels of TLR3, MDA5, and pIRF3. This study provides novel insight into a hepatoprotective effect, whereby HSP60 inhibits the release of dsRNA to repress the TLR3/MDA5/pIRF3 pathway in the context of NAFLD or hepatic inflammation. Therefore, HSP60 may serve as a possible therapeutic target for improving NAFLD.

MiR-29a Curbs Hepatocellular Carcinoma Incidence via Targeting of HIF-1α and ANGPT2.

A high-fat diet is responsible for hepatic fat accumulation that sustains chronic liver damage and increases the risks of steatosis and hepatocellular carcinoma (HCC). MicroRNA-29a (miR-29a), a key regulator of cellular behaviors, is present in anti-fibrosis and modulator tumorigenesis. However, the increased transparency of the correlation between miR-29a and the progression of human HCC is still further investigated. In this study, we predicted HIF-1α and ANGPT2 as regulators of HCC by the OncoMir cancer database and showed a strong positive correlation with HIF-1α and ANGPT2 gene expression in HCC patients. Mice fed the western diet (WD) while administered CCl4 for 25 weeks induced chronic liver damage and higher HCC incidence than without fed WD mice. HCC section staining revealed signaling upregulation in ki67, severe fibrosis, and steatosis in WD and CCl4 mice and detected Col3a1 gene expressions. HCC tissues significantly attenuated miR-29a but increased in HIF-1α, ANGPT2, Lox, Loxl2, and VEGFA expression. Luciferase activity analysis confirms that miR-29a specific binding 3'UTR of HIF-1α and ANGPT2 to repress expression. In summary, miR-29a control HIF-1α and ANGPT2 signaling in HCC formation. This study insight into a novel molecular pathway by which miR-29a targeting HIF-1α and ANGPT2 counteracts the incidence of HCC development.

Improved Fixation Stability of a Dedicated Rib Fixation System in Flail Chest: A Retrospective Study.

Background and Objectives: Flail chest typically results from major trauma to the thoracic cage and is accompanied by multiple rib fractures. It has been well documented that surgical fixation of rib fractures can decrease both morbidity and mortality rates. This study aimed to evaluate the effectiveness of a dedicated APS Rib Fixation System, which features a pre-contoured design based on anatomical rib data of the Asian population. Materials and Methods: We reviewed 43 consecutive patients, who underwent surgical stabilization for flail chest with the traditional Mini bone plate (n = 20), APS plate (n = 13), or Mini + APS (n = 10). Demographic and injury variables were documented. We used X-ray radiography to determine plate fractures and screw dislocations after surgical fixation. Results: No statistical differences were noted in the demographic or injury variables. APS plates demonstrated fewer cases of plate fractures and screw dislocations than Mini plates (OR = 0.091, p = 0.008). Conclusions: The pre-contoured design of the APS plate demonstrated a superior rib implant failure rate as compared to the traditional Mini bone plate. Our study indicates that the APS plate may serve as an effective surgical tool for the treatment of flail chest.

Successful Urgent TAVI for Critical Aortic Valve Stenosis after ECMO Implantation.

Transcatheter aortic valve implantation (TAVI) has evolved to be the treatment of choice for patients with severe aortic stenosis and high perioperative risk. Cardiogenic shock is one of the most severe complications during the TAVI procedure, especially as the prognosis of cardiogenic shock secondary to aortic stenosis is very poor. This situation can be challenging, while extracorporeal membranous oxygenation (ECMO) can be a treatment option. Here, we reported on an 88-year-old female patient who had been diagnosed as non-ST-elevation myocardial infarction (NSTEMI) and critical aortic valve stenosis (AS) with a logistic Euroscore of 25%. Percutaneous coronary angioplasty (PCI) was performed smoothly and developed tachy-brady arrhythmia of atrial fibrillation then cardiac arrest at the beginning of the TAVI procedure. A v-a ECMO was installed at her left femoral side. Afterward, the TAVI procedure was completed accordingly; her consciousness recovered and Levosimendan therapy enhanced her left-ventricular ejection fraction (LVEF) from 22% to 40%. Five days after TAVI, ECMO was replaced by intra-aortic balloon pumping (IABP) and it was removed 3 days later. A minor complication of this therapy, e.g., muscular weakness in her left leg, was noted. The patient underwent rehabilitation for about 2 months, and was discharged from hospital with a wheel chair and clear consciousness. At the 24 month follow-up she was in good recovery and was able to walk upstairs to the second floor again. Our experience suggests that one indication of prophylactic use of ECMO is for patients with an unstable hemodynamic condition.

Role of autophagy-related protein in the prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgical resection.

BACKGROUND: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). METHODS: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. RESULTS: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68-26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01-0.34), p = 0.004, and 0.07 (0.01-0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85-922), p = 0.008, and 17.9 (1.05-306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. CONCLUSION: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.