Use of consecutive transcutaneous oxygen measurement when assessing the need for revascularization and association with the outcomes of ischemic diabetic ulcers.

This study compared the ankle-brachial index (ABI) with transcutaneous oxygen pressure (TcPO2 ) in assessing peripheral vascular disease (PVD) prevalence in 100 diabetic foot ulcer (DFU) patients. Patients were categorized into vascular or nonvascular reconstruction groups and underwent both ABI and TcPO2 measurements four times over 6 months. Predictive validity for PVD diagnosis was analysed using the area under the receiver-operating characteristic curve (AUC). The study found TcPO2 to be a superior predictor of PVD than ABI. Among the DFU patients, 51 with abnormal TcPO2 values underwent vascular reconstruction. Only TcPO2 values showed significant pretreatment differences between the groups and increased post-reconstruction. These values declined over a 6-month follow-up, whereas ABI values rose. For those with end-stage renal disease (ESRD), TcPO2 values saw a sharp decrease within 3 months. Pre-reconstruction TcPO2 was notably lower in amputation patients versus limb salvage surgery patients. In conclusion, TcPO2 is more effective than ABI for evaluating ischemic limb perfusion and revascularization necessity. It should be prioritized as the primary follow-up tool, especially for ESRD patients.

Incidence of Postoperative Delirium in Cancer Patients After Head and Neck Surgery: A Proportional Meta-analysis.

OBJECTIVE: To summarize the incidence of postoperative delirium among cancer patients undergoing head and neck surgery and determine the differential incidence rates among patients undergoing different types of head and neck surgeries. DATA SOURCES: The databases of PubMed, Cochrane Library, Web of Science, EMBASE, and CINAHL were searched from inception till February 2023. Keywords based on the condition (delirium), context (postoperative), and population (head and neck cancer) were used as search terms. REVIEW METHODS: The PRISMA and MOOSE reporting guidelines were followed. The Joanna Briggs Institute critical appraisal checklists for cohort studies, case-control studies, and randomized controlled trials were used to evaluate the methodological quality. Data were pooled using a random-effects model, and the incidence with 95% confidence intervals was evaluated using the exact binomial method and Freeman-Tukey double arcsine transformation of proportions. I2 was used to indicate heterogeneity. Predefined subgroup analysis and Meta-regression, was performed to identify the factors affecting heterogeneity. RESULTS: The summary incidence of postoperative delirium was 18.95% [95% confidence interval, 14.36%-24.00%] with between-study heterogeneity (I2 = 95.46%). The incidence of postoperative delirium in patients who underwent free flap reconstruction was 22.13%, which was higher than those of other types of surgeries. Meta-regression revealed that conducted in sample size (P = .007) of the included studies was the factors affecting heterogeneity. CONCLUSIONS: The evidence on postoperative delirium incidence provided by the current Meta-analysis enables effective treatment planning.

Artificial intelligence based system for predicting permanent stoma after sphincter saving operations.

Although the goal of rectal cancer treatment is to restore gastrointestinal continuity, some patients with rectal cancer develop a permanent stoma (PS) after sphincter-saving operations. Although many studies have identified the risk factors and causes of PS, few have precisely predicted the probability of PS formation before surgery. To validate whether an artificial intelligence model can accurately predict PS formation in patients with rectal cancer after sphincter-saving operations. Patients with rectal cancer who underwent a sphincter-saving operation at Taipei Medical University Hospital between January 1, 2012, and December 31, 2021, were retrospectively included in this study. A machine learning technique was used to predict whether a PS would form after a sphincter-saving operation. We included 19 routinely available preoperative variables in the artificial intelligence analysis. To evaluate the efficiency of the model, 6 performance metrics were utilized: accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiving operating characteristic curve. In our classification pipeline, the data were randomly divided into a training set (80% of the data) and a validation set (20% of the data). The artificial intelligence models were trained using the training dataset, and their performance was evaluated using the validation dataset. Synthetic minority oversampling was used to solve the data imbalance. A total of 428 patients were included, and the PS rate was 13.6% (58/428) in the training set. The logistic regression (LR), Gaussian Naïve Bayes (GNB), Extreme Gradient Boosting (XGB), Gradient Boosting (GB), random forest, decision tree and light gradient boosting machine (LightGBM) algorithms were employed. The accuracies of the logistic regression (LR), Gaussian Naïve Bayes (GNB), Extreme Gradient Boosting (XGB), Gradient Boosting (GB), random forest (RF), decision tree (DT) and light gradient boosting machine (LightGBM) models were 70%, 76%, 89%, 93%, 95%, 79% and 93%, respectively. The area under the receiving operating characteristic curve values were 0.79 for the LR model, 0.84 for the GNB, 0.95 for the XGB, 0.95 for the GB, 0.99 for the RF model, 0.79 for the DT model and 0.98 for the LightGBM model. The key predictors that were identified were the distance of the lesion from the anal verge, clinical N stage, age, sex, American Society of Anesthesiologists score, and preoperative albumin and carcinoembryonic antigen levels. Integration of artificial intelligence with available preoperative data can potentially predict stoma outcomes after sphincter-saving operations. Our model exhibited excellent predictive ability and can improve the process of obtaining informed consent.

Tn as a potential predictor for regional lymph node metastasis in T1 colorectal cancer.

BACKGROUND: Approximately 10 percent of T1 colorectal cancer (CRC) has lymph node metastasis. In this study, we aimed to determine possible predictors for nodal involvement in order to aid selection of appropriate patients for organ-preserving strategies. METHODS: We retrospectively reviewed CRC patients underwent radical surgery from January 2009 to December 2016, with final pathology report disclosed as T1 lesion. The paraffin-embedded samples were achieved for glycosylated proteins expression analysis by immunohistochemistry. RESULTS: Totally, 111 CRC patients with T1 lesion were enrolled in this study. Of these patients, seventeen patients had nodal metastases, with the lymph node positive rate of 15.3%. Semiquantitative analysis of immunohistochemical results indicated that mean value of Tn protein expression in T1 CRC specimens was significantly different between patients with and without lymph node metastasis (63.6 vs. 27.4; p = 0.018). CONCLUSIONS: Our data shown that Tn expression may be applied as a molecular predictor for regional lymph node metastasis in T1 CRC. Moreover, the organ-preserving strategy could be improved by proper classification of patients. The mechanism involved in expression of Tn glycosylation protein and CRC metastasis need further investigation.

Clinical assessment for non-reversal stoma and stoma re-creation after reversal surgery for patients with rectal cancer having undergoing sphincter-saving operation.

BACKGROUND: This study aimed to identify the risk factors for permanent stoma (PS) in patients who underwent sphincter-saving operations for rectal cancer. METHODS: We retrospectively reviewed 597 consecutive patients with rectal cancer from January 2012 to December 2020 at Taipei Medical University Hospital. Univariate and multivariable analyses were used to analyze risk factors for PS. RESULTS: After a mean follow-up of 47.3 months (range 7-114 months), 59 patients (15.1%) were alive with a PS, including 46 patients who did not undergo reversal surgery and 13 patients who underwent stoma re-creation after reversal surgery. The mean period between primary surgery and stoma reversal was 6.0 months. Multivariate analysis revealed that the risk factors for PS were local recurrence [odd ratio (OR), 25.58; 95% confidence interval (CI), 4.428-147.761; p < 0.001], perirectal abscess [OR, 154.34; 95% CI, 15.806 - >999; p < 0.001], anastomosis site stenosis [OR, 187.081; 95% CI, 22.193 - >999; p < 0.001], perineural invasion [OR, 4.782; 95% CI, 1.22-18.736; p = 0.025], and operation time (min) [OR, 1.008; 95% CI, 1.002-1.014; p = 0.01]. CONCLUSIONS: Local recurrence, perirectal abscess, anastomosis site stenosis, perineural invasion, and operation time were independent risk factors for PS. Therefore, before a patient undergoes surgery for rectal cancer, surgeons should consider the possibility of the need for a PS, and patients should be informed before the operation that closure of the temporary stoma may not always be possible.

Psychometric properties and cross-cultural adaptation of the Indonesian version of the Brief COPE in a sample of advanced cancer patients.

The Brief COPE Inventory has been proven as acceptable psychometric properties to examine coping strategies among cancer patients. However, most psychometric testing studies have been carried out in Western countries, raising concerns about the properties' relevance and applicability in other cultural contexts. This study aimed to present psychometric properties of the Brief COPE in a sample of patients with advanced cancer in Indonesia. Specifically, we intended to examine the factorial structure and the measure's validity and reliability. This study included 440 patients from the original study who completed the Indonesian version of Brief COPE. We used exploratory factor analysis and confirmatory factor analysis to assess factor structure and evaluate the structural model fit, respectively. Reliability was demonstrated by internal consistency represented by Cronbach's alpha coefficient. The factor analysis identified a 21-items scale with 5-factors (avoidance, religion and acceptance, social support coping, problem solving and distraction). Confirmatory factor analysis demonstrated a good model fit. For the whole scale and its subscales Cronbach's alpha coefficients were acceptable signifying good reliability. Convergent, divergent validity and contrast group comparison were evidenced by significant correlations among subscales and the other instruments used. This study shows that the Indonesian version of Brief COPE is a reliable and valid instrument to measure coping in advanced cancer patients and is ready for use amongst this population in the Indonesian cultural context.

Nomogram to predict permanent stoma in rectal cancer patients after sphincter-saving surgery.

BACKGROUND: Approximately 20 percent of patients with a tumour localized in the low rectum still encounter the possibility of requiring permanent stoma (PS), which can cause drastic changes in lifestyle and physical perceptions. AIM: To determine the risk factors for PS and to develop a prediction model to predict the probability of PS in rectal cancer patients after sphincter-saving surgery. METHODS: A retrospective cohort of 421 rectal cancer patients who underwent radical surgery at Taipei Medical University Hospital between January 2012 and December 2020 was included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors for PS. A nomogram was developed according to the independent risk factors obtained in the multivariate analysis. The performance of the nomogram was assessed using a receiver operating characteristic curve and a calibration curve. RESULTS: The PS rate after sphincter-saving surgery was 15.1% (59/391) in our study after a median follow-up of 47.3 mo (range 7-114 mo). Multivariate logistic regression analysis demonstrated that local recurrence, perirectal abscess, anastomosis site stenosis, perineural invasion, tumor size and operative time were independent risk factors for PS. These identified risk factors were incorporated into the nomogram, and the concordance index of this model was 0.903 (95%CI: 0.851-0.955). According to the calibration curves, the nomogram represents a perfect prediction model. CONCLUSION: Several risk factors for PS after sphincter-saving surgery were identified. Our nomogram exhibited perfect predictive ability and will improve a physician's ability to communicate the benefits and risks of various treatment options in shared decision making.

Determinants of coronavirus disease 2019 infection by artificial intelligence technology: A study of 28 countries.

OBJECTIVES: The coronavirus disease 2019 pandemic has affected countries around the world since 2020, and an increasing number of people are being infected. The purpose of this research was to use big data and artificial intelligence technology to find key factors associated with the coronavirus disease 2019 infection. The results can be used as a reference for disease prevention in practice. METHODS: This study obtained data from the "Imperial College London YouGov Covid-19 Behaviour Tracker Open Data Hub", covering a total of 291,780 questionnaire results from 28 countries (April 1~August 31, 2020). Data included basic characteristics, lifestyle habits, disease history, and symptoms of each subject. Four types of machine learning classification models were used, including logistic regression, random forest, support vector machine, and artificial neural network, to build prediction modules. The performance of each module is presented as the area under the receiver operating characteristics curve. Then, this study further processed important factors selected by each module to obtain an overall ranking of determinants. RESULTS: This study found that the area under the receiver operating characteristics curve of the prediction modules established by the four machine learning methods were all >0.95, and the RF had the highest performance (area under the receiver operating characteristics curve is 0.988). Top ten factors associated with the coronavirus disease 2019 infection were identified in order of importance: whether the family had been tested, having no symptoms, loss of smell, loss of taste, a history of epilepsy, acquired immune deficiency syndrome, cystic fibrosis, sleeping alone, country, and the number of times leaving home in a day. CONCLUSIONS: This study used big data from 28 countries and artificial intelligence methods to determine the predictors of the coronavirus disease 2019 infection. The findings provide important insights for the coronavirus disease 2019 infection prevention strategies.

Plasmablastic myeloma in Taiwan frequently presents with extramedullary and extranodal mass mimicking plasmablastic lymphoma.

Plasmablastic myeloma (PBM) is a blastic morphologic variant of plasma cell myeloma with less favorable prognosis than those with non-blastic morphology. PBM is rare, without clear-cut definition and detailed clinicopathologic features in the literature. PBM may mimic plasmablastic lymphoma (PBL) as they share nearly identical morphology and immunophenotype. Using the criteria of ≥ 30% plasmablasts in tissue sections, we retrospectively recruited PBM cases and analyzed their clinical, imaging, and pathologic findings, with emphasis on extramedullary involvement. We performed immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBER), and fluorescence in situ hybridization (FISH) for lymphoma- and myeloma-associated genetic alterations. Of the 25 recruited cases, 15 (60%) had extramedullary involvement, which occurred as initial presentation in nine cases. The most common extramedullary sites were soft tissue and/or skin (10/15, 67%), followed by pleural effusion, the lungs, and lymph nodes. Immunohistochemically, tumor cells expressed MYC (74%; 17/23), CD56 (56%; 14/25), and cyclin D1 (16%; 4/25), while CD117 was all negative (n = 25). Of the 20 cases stained with p53, four (20%) cases were diffusely positive, and the remaining 16 cases showed a heterogeneous pattern. EBER was negative in all 24 cases examined. Of the 13 cases examined with FISH, the genetic aberrations identified included del(13q14)(92%; 12/13), gain of chromosome 1q (90%; 9/10), loss of chromosome 1p (60%; 6/10), IGH-FGFR3 reciprocal translocation (23%; 3/13), rearranged MYC (15%; 2/13), and rearranged CCND1 (8%; 1/13), while there were no cases with TP53 deletion (n = 10) or rearrangement of BCL2 (n = 13) or BCL6 (n = 13). The prognosis was dismal regardless of the presence or absence of extramedullary involvement. In conclusion, PBM in Taiwan frequently presented as extramedullary and extranodal lesions, particularly in soft tissue and/or skin, mimicking PBL. FISH for targeted genetic alterations such as del(13q14), gain of chromosome 1q, loss of chromosome 1p, and IGH-FGFR3 might be helpful for the differential diagnoses. Larger studies are warranted to investigate the genetic alterations between PBM and PBL.

Knowledge of and Barriers to Palliative Care Perceived by Healthcare Providers before and after Promotion of the Patient Autonomy Act: A Cross-Sectional Study.

This study was designed to investigate healthcare providers' knowledge of palliative care and perceptions of palliative care barriers before and after promoting the Patient Autonomy Act (PAA). A convenience sample was recruited, including 277 healthcare providers in 2013 and 222 healthcare providers in 2018. Multivariate linear regression analyses were used to identify predictors of knowledge of and perceived barriers to palliative care. A principal component analysis was carried out to identify the most appropriate factorial structure for the contents of knowledge and perceived barriers to palliative care. Three factors related to knowledge of palliative care were identified in both 2013 and 2018 data: 'policy, regulation, and promotion', 'philosophy and treatments', and 'myths and misunderstandings'. Study findings for the two periods were similar. As for barriers to providing palliative care, three factors were identified for 2013: 'quality care', 'difficulties' and 'communication', and for 2018, 'information', 'attitudes' and 'quality care' were identified. Study findings differed between the two periods. Policies can better reinforce mitigating strategies-including opportunities for education, shared decision making, and changes in institutions and care systems. Additionally, assessing barriers creates important opportunities for further research to address the most critical aspects in improving end-of-life care for patients and their families.

Relationship between predisposing and facilitating factors: Does it influence the risk of developing peri-operative pressure injuries?

This study examined the relationship between the personal predisposing factors of patients and the severity of pressure injuries (PIs) developed during surgery. This retrospective cohort study collected 439 cases of peri-operative PIs. Using binary logistic regression to identify the variables associated with PI severity, the effects of interactions between associated variables were then tested. The results of this study revealed that among the personal predisposing factors, only higher patient age (P = .001) and higher body mass index (P < .001) posed a greater risk of stage 2 PIs or higher. Among the surgery-related facilitating factors, only patients who were placed in the prone position during surgery and patients who lost ≥1000 mL of blood during surgery were at greater risk of stage 2 PIs or higher, compared, respectively, to those placed in the supine position and those who lost ≤100 mL of blood. Furthermore, the amount of blood lost during surgery moderated the influence of age on PI severity. For elderly patients who are expected to lose a large blood volume during surgery or lose an immeasurable amount of blood due to the use of cardiopulmonary bypass, taking more precautionary measures to prevent PIs is recommended.

Apolipoprotein (a)/Lipoprotein(a)-Induced Oxidative-Inflammatory α7-nAChR/p38 MAPK/IL-6/RhoA-GTP Signaling Axis and M1 Macrophage Polarization Modulate Inflammation-Associated Development of Coronary Artery Spasm.

OBJECTIVE: Apolipoprotein (a)/lipoprotein(a) (Lp(a)), a major carrier of oxidized phospholipids, and α7-nicotinic acetylcholine receptor (α7-nAChR) may play an important role in the development of coronary artery spasm (CAS). In CAS, the association between Lp(a) and the α7-nAChR-modulated inflammatory macrophage polarization and activation and smooth muscle cell dysfunction remains unknown. METHODS: We investigated the relevance of Lp(a)/α7-nAChR signaling in patient monocyte-derived macrophages and human coronary artery smooth muscle cells (HCASMCs) using expression profile correlation analyses, fluorescence-assisted cell sorting flow cytometry, immunoblotting, quantitative real-time polymerase chain reaction, and clinicopathological analyses. RESULTS: There are increased serum Lp(a) levels (3.98-fold, p = 0.011) and macrophage population (3.30-fold, p = 0.013) in patients with CAS compared with patients without CAS. Serum Lp(a) level was positively correlated with high-sensitivity C-reactive protein (r 2 = 0.48, p < 0.01), IL-6 (r 2 = 0.38, p = 0.03), and α7-nAChR (r 2 = 0.45, p < 0.01) in patients with CAS, but not in patients without CAS. Compared with untreated or low-density lipoprotein- (LDL-) treated macrophages, Lp(a)-treated macrophages exhibited markedly enhanced α7-nAChR mRNA expression (p < 0.01) and activity (p < 0.01), in vitro and ex vivo. Lp(a) but not LDL preferentially induced CD80+ macrophage (M1) polarization and reduced the inducible nitric oxide synthase expression and the subsequent NO production. While shRNA-mediated loss of α7-nAChR function reduced the Lp(a)-induced CD80+ macrophage pool, both shRNA and anti-IL-6 receptor tocilizumab suppressed Lp(a)-upregulated α7-nAChR, p-p38 MAPK, IL-6, and RhoA-GTP protein expression levels in cultures of patient monocyte-derived macrophages and HCASMCs. CONCLUSIONS: Elevated Lp(a) levels upregulate α7-nAChR/IL-6/p38 MAPK signaling in macrophages of CAS patients and HCASMC, suggesting that Lp(a)-triggered inflammation mediates CAS through α7-nAChR/p38 MAPK/IL-6/RhoA-GTP signaling induction, macrophage M1 polarization, and HCASMC activation.

Pterostilbene Increases LDL Metabolism in HL-1 Cardiomyocytes by Modulating the PCSK9/HNF1α/SREBP2/LDLR Signaling Cascade, Upregulating Epigenetic hsa-miR-335 and hsa-miR-6825, and LDL Receptor Expression.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) can promote the degradation of low-density lipoprotein (LDL) receptor (LDLR), leading to hypercholesterolemia and myocardial dysfunction. The intracellular regulatory mechanism by which the natural polyphenol pterostilbene modulates the PCSK9/LDLR signaling pathway in cardiomyocytes has not been evaluated. We conducted Western blotting, flow cytometry, immunofluorescence staining, and mean fluorescence intensity analyses of pterostilbene-treated mouse HL-1 cardiomyocytes. Pterostilbene did not alter cardiomyocyte viability. Compared to the control group, treatment with both 2.5 and 5 µM pterostilbene significantly increased the LDLR protein expression accompanied by increased uptake of LDL. The expression of the mature PCSK9 was significantly suppressed at the protein and mRNA level by the treatment with both 2.5 and 5 µM pterostilbene, respectively, compared to the control. Furthermore, 2.5 and 5 µM pterostilbene treatment resulted in a significant reduction in the protein hepatic nuclear factor 1α (HNF1α)/histone deacetylase 2 (HDAC2) ratio and sterol regulatory element-binding protein-2 (SREBP2)/HDAC2 ratio. The expression of both hypoxia-inducible factor-1 α (HIF1α) and nuclear factor erythroid 2-related factor 2 (Nrf2) at the protein level was also suppressed. Pterostilbene as compared to short hairpin RNA against SREBP2 induced a higher protein expression of LDLR and lower nuclear accumulation of HNF1α and SREBP2. In addition, pterostilbene reduced PCSK9/SREBP2 interaction and mRNA expression by increasing the expression of hsa-miR-335 and hsa-miR-6825, which, in turn, increased LDLR mRNA expression. In cardiomyocytes, pterostilbene dose-dependently decreases and increases the protein and mRNA expression of PCSK9 and LDLR, respectively, by suppressing four transcription factors, HNF1α, SREBP2, HIF1α, and Nrf2, and enhancing the expression of hsa-miR-335 and hsa-miR-6825, which suppress PCSK9/SREBP2 interaction.

Small blood stem cells for enhancing early osseointegration formation on dental implants: a human phase I safety study.

BACKGROUND: Small blood stem cells (SB cells), isolated from human peripheral blood, demonstrated the ability to benefit bone regeneration and osseointegration. The primary goal of our study is to examine the safety and tolerability of SB cells in dental implantation for human patients with severe bone defects. METHODS: Nine patients were enrolled and divided into three groups with SB cell treatment doses of 1 × 105, 1 × 106, and 1 × 107 SB cells, and then evaluated by computed tomography (CT) scans to assess bone mineral density (BMD) by Hounsfield units (HU) scoring. Testing was conducted before treatment and on weeks 4, 6, 8, and 12 post dental implantation. Blood and comprehensive chemistry panel testing were also performed. RESULTS: No severe adverse effects were observed for up to 6-month trial. Grade 1 leukocytosis, anemia, and elevated liver function were observed, but related with the patient's condition or the implant treatment itself and not the transplantation of SB cells. The levels of cytokines and chemokines were detected by a multiplex immunological assay. Elevated levels of eotaxin, FGF2, MCP-1, MDC, and IL17a were found among patients who received SB cell treatment. This observation suggested SB cells triggered cytokines and chemokines for local tissue repair. To ensure the efficacy of SB cells in dental implantation, the BMD and maximum stresses via stress analysis model were measured through CT scanning. All patients who suffered from severe bone defect showed improvement from D3 level to D1 or D2 level. The HU score acceleration can be observed by week 2 after guided bone regeneration (GBR) and prior to dental implantation. CONCLUSIONS: This phase I study shows that treatment of SB cells for dental implantation is well tolerated with no major adverse effects. The use of SB cells for accelerating the osseointegration in high-risk dental implant patients warrants further phase II studies. TRIAL REGISTRATION: Taiwan Clinical Trial Registry ( SB-GBR001 ) and clinical trial registry of the United States ( NCT04451486 ).

Garcinol Attenuates Lipoprotein(a)-Induced Oxidative Stress and Inflammatory Cytokine Production in Ventricular Cardiomyocyte through α7-Nicotinic Acetylcholine Receptor-Mediated Inhibition of the p38 MAPK and NF-κB Signaling Pathways.

Garcinol, a nicotinic acetylcholine receptor (nAChR) antagonist, has recently been established as an anti-inflammation agent. However, the molecular mechanism by which garcinol suppresses inflammation in the context of acute myocardial infarction (AMI) remains unclear. Hypothesis: We hypothesized that the administration of physiological doses of garcinol in mice with isoproterenol-induced AMI decreased the effect of lipoprotein(a) (Lp(a))-induced inflammation both in vivo and in vitro via the α7-nAChRs mediated p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway. We analyzed altered reactive oxygen species (ROS) generation, the production of superoxide by mitochondria, cytokine expression patterns, and the role of the p38 MAPK/NF-κB signaling pathway after Lp(a)-stimulated human ventricular cardiomyocyte AC16 cells were treated with increasing doses of garcinol. C-reactive protein (CRP), interleukin (IL)-1ß, IL-6, or tumor necrosis factor (TNF)-α production were detected by enzyme-linked immunosorbent assay. The Cell Counting Kit-8 assay was used to evaluate drug cytotoxicity. Western blots and confocal fluorescence microscopy were used to determine altered expression patterns of inflammatory biomarkers. We also examined whether the therapeutic effect of garcinol in AMI was mediated in part by α7-nAChR. Lp(a)-induced inflammatory cardiomyocytes had increased expression of membrane-bound α7-nAChRs in vitro and in vivo. Low-dose garcinol did not affect cardiomyocyte viability but significantly reduced mitochondrial ROS, CRP, IL-1ß, IL-6, and TNF-α production in Lp(a)-stimulated cardiomyocytes (p < 0.05). The Lp(a)-induced phosphorylation of p38 MAPKs, CamKII, and NFκB, as well as NFκB-p65 nuclear translocation, was also suppressed (p < 0.05) by garcinol, while the inhibition of p38 MAPK by the inhibitor SB203580 decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK. Garcinol protected cardiomyocytes by inhibiting apoptosis and inflammation in mice with AMI. Furthermore, garcinol also enhanced the expression of microRNA-205 that suppressed the α7-nAChR-induced p38 MAPK/NF-κB signaling pathway. Garcinol suppresses Lp(a)-induced oxidative stress and inflammatory cytokines by α7-nAChR-mediated inhibition of p38 MAPK/NF-κB signaling in cardiomyocyte AC16 cells and isoproterenol-induced AMI mice.

Hiltonol Cocktail Kills Lung Cancer Cells by Activating Cancer-Suppressors, PKR/OAS, and Restraining the Tumor Microenvironment.

NSCLC (non-small cell lung cancer) is a leading cause of cancer-related deaths worldwide. Clinical trials showed that Hiltonol, a stable dsRNA representing an advanced form of polyI:C (polyinosinic-polycytidilic acid), is an adjuvant cancer-immunomodulator. However, its mechanisms of action and effect on lung cancer have not been explored pre-clinically. Here, we examined, for the first time, how a novel Hiltonol cocktail kills NSCLC cells. By retrospective analysis of NSCLC patient tissues obtained from the tumor biobank; pre-clinical studies with Hiltonol alone or Hiltonol+++ cocktail [Hiltonol+anti-IL6+AG490 (JAK2 inhibitor)+Stattic (STAT3 inhibitor)]; cytokine analysis; gene knockdown and gain/loss-of-function studies, we uncovered the mechanisms of action of Hiltonol+++. We demonstrated that Hiltonol+++ kills the cancer cells and suppresses the metastatic potential of NSCLC through: (i) upregulation of pro-apoptotic Caspase-9 and Caspase-3, (ii) induction of cytosolic cytochrome c, (iii) modulation of pro-inflammatory cytokines (GRO, MCP-1, IL-8, and IL-6) and anticancer IL-24 in NSCLC subtypes, and (iv) upregulation of tumor suppressors, PKR (protein kinase R) and OAS (2'5' oligoadenylate synthetase). In silico analysis showed that Lys296 of PKR and Lys66 of OAS interact with Hiltonol. These Lys residues are purportedly involved in the catalytic/signaling activity of the tumor suppressors. Furthermore, knockdown of PKR/OAS abrogated the anticancer action of Hiltonol, provoking survival of cancer cells. Ex vivo analysis of NSCLC patient tissues corroborated that loss of PKR and OAS is associated with cancer advancement. Altogether, our findings unraveled the significance of studying tumor biobank tissues, which suggests PKR and OAS as precision oncological suppressor candidates to be targeted by this novel Hiltonol+++ cocktail which represents a prospective drug for development into a potent and tailored therapy for NSCLC subtypes.

Lifestyle and behavioral modifications made by patients with interstitial cystitis.

Interstitial cystitis/bladder pain syndrome (IC/BPS) negatively affects the quality of life. In this study, we investigated the lifestyle behavioral changes patients with IC/BPS make to cope with their symptoms. This prospective study was conducted between August 2018 and June 2019. All patients had a primary symptom of suprapubic pain with a full bladder and other lower urinary tract symptoms for more than 6 weeks as well as cystoscopic findings. All participants completed our self-developed questionnaire, which included informations about their living and work environment, occupational garments, dietary habits, and personal habits. Continuous variables were compared using an independent sample t test, and categorical variables were compared using a chi-square test. We recruited 86 patients with IC/BPS and age-matched 86 controls without IC/BPS. In our study, patients with IC/BPS had more cranberry intake (45.34% vs. 5.81%, P < 0.05) than non-IC/BPS controls; the IC/BPS group had decreased consumption of coffee and spicy food; and wore less makeup or special work garments. In conclusion, patients with IC/BPS tend to make several lifestyle behavioral changes to cope with their symptoms.

SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA-LIHC patients (n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and ALDH2. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with 'normal' paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.

Interleukin 8 may predict surgical necrotizing enterocolitis in infants born less than 1500 g.

Necrotizing enterocolitis (NEC) often leads to gastrointestinal emergency resulting high mortality in very low birth weight infants (VLBWIs) requiring surgery. To date, few studies have explored the role of serum cytokines in the development of feeding intolerance (FI) or NEC outcomes in VLBWIs. Infants born weighing <1500 g or of 32 weeks of gestational age were prospectively enrolled from May 2018 to Dec 2019. We measured several cytokines routinely within 72 h of life, even before NEC-like symptoms developed. NEC or FI group comprised 17 (27.4%) infants, and 6 (9.7%) infants had surgical NEC. The gestational age and birth weight were significantly lower in the NEC or FI group with more prematurity-related complications. The surgical NEC group also demonstrated significantly lower gestational age and birth weight along with more infants experiencing refractory hypotension within a 1 week of life, pulmonary hypertension, and patent ductus arteriosus. IL-10 levels were significantly higher in the NEC or FI group, whereas IL-8 levels were significantly higher in the infants with surgical NEC. Our findings indicated to IL-8 can predict surgical NEC while increased IL-10 can predict NEC development in VLBWIs.

Long-term outcomes of metabolic surgery in overweight and obese patients with type 2 diabetes in Asia.

AIM: To assess the outcomes of metabolic surgery in overweight and obese patients in Asia with type 2 diabetes (T2D). MATERIALS AND METHODS: The treatment outcomes of 1999 patients from the Asian Diabetes Surgery Summit database were analysed. The changes in treatment effects across time were assessed with respect to the surgical procedures performed by using generalized estimating equations. RESULTS: The most commonly performed procedure was the single-anastomosis gastric bypass (32.6%). Weight (from 106.2 ± 25.1 to 77.9 ± 18.8 kg), body mass index (BMI; from 38.7 ± 7.9 to 28.5 ± 5.9 kg/m2 ), blood sugar (from 9.3 ± 4.1 to 5.7 ± 1.8 mmol/L) and HbA1c (from 8.4% ± 1.8% to 6.0% ± 1.1%) significantly improved from baseline to 1 year (P < .001) and remained stable at 5 years (weight, 86.3 ± 23.3 kg; BMI, 31.7 ± 7.9 kg/m2 ; blood sugar, 5.8 ± 1.8 mmol/L, and HbA1c, 6.4% ± 1.2%; all P < .001 vs. baseline). Blood pressure and most lipid disorders also improved significantly. Of the treatment procedures, single-anastomosis gastric bypass had the most satisfactory outcomes with statistical significance for most disorders, whereas adjustable gastric banding displayed the least satisfactory outcomes. CONCLUSIONS: Metabolic surgery remarkably improved body weight, T2D and other metabolic disorders in Asian patients. However, the efficacy of individual procedures varied substantially.