Impact of glucose-containing fluid on acute pancreatitis outcomes: A multicenter retrospective analysis.

INTRODUCTION: Fluid resuscitation reduces mortality and morbidity in acute pancreatitis (AP); however, whether glucose-containing fluids negatively impact AP remains uncertain. We aimed to examine the association between glucose-containing fluids and AP outcomes. METHODS: This multicenter retrospective cohort study included patients diagnosed with AP between January 2015 and December 2018. Glucose density was defined as total glucose content divided by total fluid volume (g/dl) on day 1, and was considered high if the level exceeded the median. Endpoints were early organ failure (OF), including cardiovascular, renal, or respiratory system failure within 7 days; 30-day OF; ICU admission; and AP-related 90-day mortality. Logistic regression models, restricted cubic spline curves, and Cox proportional hazards models were used for statistical analysis. RESULTS: From the database, 1,146 patients with AP were included. Early OF occurred in 8.8% of patients within 7 days. The high glucose-density group (>5 g/dl) had increased risk of early OF (9.7% vs. 8.2%; adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.03-2.80; P = 0.039), respiratory failure (8.0% vs. 6.2%; aOR, 1.88; 95% CI, 1.09-3.24; P = 0.024), cardiovascular failure (3.4% vs. 2.4%; aOR, 3.59; 95% CI, 1.28-10.0; P = 0.015), and ICU admission (6.8% vs. 5.8%; aOR, 2.06; 95% CI, 1.08-3.94; P = 0.029), with a dose-response effect observed for cardiovascular failure and ICU admission. A significant increase 30-day OF risk (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.19-2.45) was also noted. CONCLUSION: Excess glucose-containing fluid was associated with increased risks of overall, respiratory, and cardiovascular OF and ICU admission in AP.

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.

Prenatal and early-life antibiotic exposure and the risk of atopic dermatitis in children: A nationwide population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) contributes to substantial social and financial costs in public health care systems. Antibiotic exposure during pregnancy has been proposed as a risk factor, but findings remain inconsistent. The aim of this study was to investigate the association between prenatal antibiotic use and childhood AD. METHODS: We performed a population-based cohort study using data collected from the Taiwan Maternal and Child Health Database from 2009 to 2016. Associations were determined using Cox proportional hazards model and were adjusted for several potential covariates, including maternal atopic disorders and gestational infections. Children with and without maternal predispositions of atopic diseases and postnatal antibiotic/acetaminophen exposures within 1 year were stratified to identify the subgroups at risk. RESULTS: A total of 1,288,343 mother-child pairs were identified and 39.5% received antibiotics prenatally. Maternal antibiotic use during pregnancy was slightly positively associated with childhood AD (aHR 1.04, 95% CI 1.03-1.05), especially in the first and second trimesters. An apparent dose-response pattern was observed with an 8% increased risk when the exposure was ≥5 courses prenatally (aHR 1.08, 95% CI 1.06-1.11). Subgroup analysis showed the positive association remained significant regardless of postnatal infant antibiotic use, but the risk attenuated to null in infants who were not exposed to acetaminophen (aHR 1.01, 95% CI 0.96-1.05). The associations were higher in children whose mothers were without AD compared to those whose mothers were with AD. In addition, postnatal antibiotic or acetaminophen exposure of infants was associated with an increased risk of developing AD after 1 year of age. CONCLUSION: Maternal antibiotic use during pregnancy was associated with an increased risk of childhood AD in a dose-related manner. Further research may be warranted to investigate this variable using a prospectively designed study, and also to examine whether or not this association is specifically related to pregnancy.

A protein-based subunit vaccine with biological adjuvants provides effective protection against Pasteurella multocida in pigs.

Streptococcus suis (S. suis) and Pasteurella multocida (P. multocida) are pathogens that can cause zoonotic diseases. P. multocida toxin (PMT) is an important virulence factor that causes atrophic rhinitis in pigs. Suilysin (Sly) is an extracellular protein of S. suis and has been shown to be a potential adjuvant. Previous studies have indicated that subunit vaccines containing several fragments of PMT as antigens are safer than traditional inactivated or live-attenuated vaccines. However, protein-based vaccines need strong adjuvants to enhance their immunogenicity. In this study, recombinant PMT-NC (rPMT-NC) protein antigen was formulated with either recombinant Sly (rSly) or CpG oligodeoxynucleotides (CpG) as the adjuvant. The immune responses elicited by these vaccines and the protective efficacy after challenge with live P. multocida were evaluated in piglets. In the dose-dependent test, piglets immunized with the low dose (100 µg) of rSly had increased antigen-specific total IgG, interferon (IFN)-γ gene expression, and CD4+ and CD8+ T-cell populations. Compared to piglets in the commercial (Al-gel) adjuvant and the control groups (p < 0.05), piglets in the biological adjuvant groups showed significantly reduced turbinate atrophy, nasal distortion, and lung lesion scores after challenge with P. multocida serotype A. Vaccines containing rSly or CpG adjuvant enhanced humoral and cellular immune responses and protection against P. multocida. This combination of a protein-based antigen formulated with a biological adjuvant showed synergistic and protective effects against atrophic rhinitis and has potential to be developed as part of a bivalent vaccine.

High-level expression of functional Pfu DNA polymerase recombinant protein by mimicking the enhanced green fluorescence protein gene codon usage.

Pfu DNA polymerase is a vital enzyme in PCR-related experiments. However, it is not easy to achieve high-level expression and high purity through one-step purification. This paper illustrates the method to acquire the full-length open reading frame of Pfu DNA polymerase. Without altering its amino acids, we have modified the codon usage, based on that of the enhanced green fluorescence protein (eGFP), and named it rPfu. The synthesized rPfu gene has been subcloned into the pET28a plasmid and expressed in four Escherichia coli strains without the pLysS plasmid. Three strains have expressed a high level of soluble Pfu DNA polymerase. With the aid of Ni-NTA His•Bind® resin, we could obtain high purity (>95%) soluble recombinant protein. Compared with the commercial, proofreading DNA polymerase, rPfu's bioactivity was 12,987 U/mg; that is, 88,311 U of rPfu could be obtained from 50 mL cultured E. coli. The purified rPfu was able to amplify the length of DNA fragments at least 5.5 kb. The method of increasing soluble protein's yield using the eGFP codon usage may introduce a new possibility to the expression of other soluble recombinant proteins.

Efficacy of carbon dioxide laser and caustic agent cauterisation for the focal granular myringitis: A randomised trial.

OBJECTIVES: Granular myringitis (GM) is a troublesome disease with a high incidence of recurrence and relapse. CO2 laser vaporisation and trichloroacetic acid (TAA) have been applied in treating several otological diseases, both with favourable therapeutic efficacy. However, long-term therapeutic efficacy of both CO2 laser vaporisation and TAA cauterisation against GM has not yet been evaluated. We aimed to investigate the therapeutic potential of CO2 laser vaporisation and TAA cauterisation in GM management. STUDY DESIGN: Prospective and randomised study. PARTICIPANTS: A total of 88 GM patients who failed therapy with boric acid, alcohol and glycerin ear drop otic solution between July 2009 and January 2018 were included. Participants were randomly assigned to receive CO2 laser vaporisation (n = 39) or TAA cauterisation (n = 49). MAIN OUTCOME MEASURES: Main outcomes were treatment success, complications after 4 months of treatment, and recurrence within 4-12 months after treatment. RESULTS: The success rate was significantly higher in the CO2 group than in the TAA group (94.9% vs. 77.6%, p = .023). After 4 months of treatment, the GM recurrence rate was comparable between the two groups (13.5% vs. 18.4%, p = .562). The CO2 laser group had one case of perforation and one case of severe vertigo, whereas one participant in the TAA cauterisation group experienced hearing loss. CONCLUSION: Both TAA cauterisation and CO2 laser vaporisation are safe and effective treatments for GM. The success rate of CO2 laser vaporisation for treating GM is higher than that of TAA cauterisation. Recurrence rates are comparable within 1 year.

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.

Highly Sensitive, Robust, and Recyclable TiO2/AgNP Substrate for SERS Detection.

Label-free biosensors provide an important platform for detecting chemical and biological substances without needing extra labeling agents. Unlike surface-based techniques such as surface plasmon resonance (SPR), interference, and ellipsometry, surface-enhanced Raman spectroscopy (SERS) possesses the advantage of monitoring analytes both on surfaces and in solutions. Increasing the SERS enhancement is crucial to preparing high-quality substrates without quickly losing their stability, sensitivity, and repeatability. However, fabrication methods based on wet chemistry, nanoimprint lithography, spark discharge, and laser ablation have drawbacks of waste of time, complicated processes, or nonreproducibility in surface topography. This study reports the preparation of recyclable TiO2/Ag nanoparticle (AgNP) substrates by using simple arc ion plating and direct-current (dc) magnetron sputtering technologies. The deposited anatase-phased TiO2 ensured the photocatalytic degradation of analytes. By measuring the Raman spectra of rhodamine 6G (R6G) in titrated concentrations, a limit of detection (LOD) of 10-8 M and a SERS enhancement factor (EF) of 1.01 × 109 were attained. Self-cleaning was performed via UV irradiation, and recyclability was achieved after at least five cycles of detection and degradation. The proposed TiO2/AgNP substrates have the potential to serve as eco-friendly SERS enhancers for label-free detection of various chemical and biological substances.

Health literacy and cancer screening behaviors among community-dwelling female adults in Taiwan.

This study was designed to explore the association among health literacy and cancer screening behaviors in Taiwanese females. A total of 353 community-dwelling females were recruited in this cross-sectional study from February to October 2015. Demographic, socioeconomic and personal behavior variables including physical activity, community activity, smoking, alcohol consumption, and betel nut chewing were recorded. Health literacy was evaluated using the Mandarin version of the European Health Literacy Survey Questionnaire. Data on screening behaviors for cervical, breast and colorectal cancers were confirmed by the Taiwanese National eHealth Database. Most respondents with inadequate or problematic general health literacy had no or irregular screening behaviors for cervical, breast and colorectal cancers. In multivariable regression analysis, women with inadequate health literacy were at a greater risk (Odds ratio = 5.71; 95% CI: 1.40-23.26) of having no previous Pap smear screening or >3 years screening interval regardless of education level. However, this association was not detected for breast or colorectal cancer. Women with inadequate health literacy were more likely to have irregular cervical cancer screening, however no associations among health literacy and breast or colorectal cancer were detected. The impact of health literacy on cancer screening behavior warrants further attention and research.

Epigenetic Regulation of Breast Cancer Stem Cells Contributing to Carcinogenesis and Therapeutic Implications.

Globally, breast cancer has remained the most commonly diagnosed cancer and the leading cause of cancer death among women. Breast cancer is a highly heterogeneous and phenotypically diverse group of diseases, which require different selection of treatments. Breast cancer stem cells (BCSCs), a small subset of cancer cells with stem cell-like properties, play essential roles in breast cancer progression, recurrence, metastasis, chemoresistance and treatments. Epigenetics is defined as inheritable changes in gene expression without alteration in DNA sequence. Epigenetic regulation includes DNA methylation and demethylation, as well as histone modifications. Aberrant epigenetic regulation results in carcinogenesis. In this review, the mechanism of epigenetic regulation involved in carcinogenesis, therapeutic resistance and metastasis of BCSCs will be discussed, and finally, the therapies targeting these biomarkers will be presented.

Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer.

Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related mortality in women worldwide. Breast cancer is fairly heterogeneous and reveals six molecular subtypes: luminal A, luminal B, HER2+, basal-like subtype (ER-, PR-, and HER2-), normal breast-like, and claudin-low. Breast cancer screening and early diagnosis play critical roles in improving therapeutic outcomes and prognosis. Mammography is currently the main commercially available detection method for breast cancer; however, it has numerous limitations. Therefore, reliable noninvasive diagnostic and prognostic biomarkers are required. Biomarkers used in cancer range from macromolecules, such as DNA, RNA, and proteins, to whole cells. Biomarkers for cancer risk, diagnosis, proliferation, metastasis, drug resistance, and prognosis have been identified in breast cancer. In addition, there is currently a greater demand for personalized or precise treatments; moreover, the identification of novel biomarkers to further the development of new drugs is urgently needed. In this review, we summarize and focus on the recent discoveries of promising macromolecules and cell-based biomarkers for the diagnosis and prognosis of breast cancer and provide implications for therapeutic strategies.

MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients.

(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan-Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer.

Estrogen modulates mesenchyme-epidermis interactions in the adult nipple.

Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, the specific pathways involved remain to be identified. By recombining cells from the ventral skin of the K14-PTHrP transgenic mice [which overexpress parathyroid hormone-related protein (PTHrP) in their developing epidermis and mammary glands] with those from wild type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipple-like epidermis. To identify candidate nipple-specific signaling factors, we compared gene expression signatures of sorted Pdgfrα-positive ventral K14-PTHrP and wild-type fibroblasts, identifying differentially expressed transcripts that are involved in WNT, HGF, TGFß, IGF, BMP, FGF and estrogen signaling. Considering that some of the growth factor pathways are targets for estrogen regulation, we examined the upstream role of this hormone in maintaining the nipple. Ablation of estrogen signaling through ovariectomy produced nipples with abnormally thin epidermis, and we identified TGFß as a negatively regulated target of estrogen signaling. Estrogen treatment represses Tgfß1 at the transcript and protein levels in K14-PTHrP fibroblasts in vitro, while ovariectomy increases Tgfb1 levels in K14-PTHrP ventral skin. Moreover, ectopic delivery of Tgfß1 protein into nipple connective tissue reduced epidermal proliferation. Taken together, these results show that specialized nipple epidermis is maintained by estrogen-induced repression of TGFß signaling in the local fibroblasts.

Taiwanese consensus recommendations for acute pancreatitis.

The incidence of acute pancreatitis and related health care utilization are increasing. Acute pancreatitis may result in organ failure and various local complications with risks of morbidity and even mortality. Recent advances in research have provided novel insights into the assessment and management for acute pancreatitis. This consensus is developed by Taiwan Pancreas Society to provide an updated, evidence-based framework for managing acute pancreatitis.

Fabrication of Double Emission Enhancement Fluorescent Nanoparticles with Combined PET and AIEE Effects.

The major challenge in the fabrication of fluorescent silica nanoparticles (FSNs) based on dye-doped silica nanoparticles (DDSNs) is aggregation-caused fluorescence quenching. Here, we constructed an FSN based on a double emission enhancement (DEE) platform. A thio-reactive fluorescence turn-on molecule, N-butyl-4-(4-maleimidostyryl)-1,8-naphthalimide (CS), was bound to a silane coupling agent, (3-mercaptopropyl)-trimethoxysilane (MPTMS), and the product N-butyl-4-(3-(trimethoxysilyl-propylthio)styryl)-1,8-naphthalimide (CSP) was further used to fabricate a core-shell nanoparticle through the Stöber method. We concluded that the turn-on emission by CSP originated from the photoinduced electron transfer (PET) between the maleimide moiety and the CSP core scaffold, and the second emission enhancement was attributed to the aggregation-induced emission enhancement (AIEE) in CSP when encapsulated inside a core-shell nanoparticle. Thus, FSNs could be obtained through DEE based on a combination of PET and AIEE effects. Systematic investigations verified that the resulting FSNs showed the traditional solvent-independent and photostable optical properties. The results implied that the novel FSNs are suitable as biomarkers in living cells and function as fluorescent visualizing agents for intracellular imaging and drug carriers.

Fundamental steps toward next-generation intelligent automatic process in a faster and cost-effective chain for processing optical surfaces.

In the context of industry 4.0, building data clouds in manufacturing technologies is the fundamental step to approach intelligent automatic process. This new technology has proved to efficiently and effectively monitor five important responses (removal rate, texture, surface accuracy, edge-profiles and mid-spatial frequencies) with more than 95% repeatability in real time. This faster and inexpensive process can serve for the nowadays high-quality segmented telescopes. We illustrate the underlying problem by reference to a case-study - the challenge of an average manufacturing rate of 11.4 segments per month for the 39.3m optical/infrared European Extremely Large Telescope (E-ELT) project.

Urinary trypsinogen-2 level and local complications of acute pancreatitis.

BACKGROUND AND AIM: Local complications of acute pancreatitis (AP) carry risks of morbidity/mortality. This study aimed to assess whether urinary trypsinogen-2 levels and Bedside Index for Severity in Acute Pancreatitis (BISAP) score on admission predicted subsequent local complications. METHODS: One hundred and forty-four consecutive patients with AP were prospectively followed till 6 months after discharge. Urinary trypsinogen-2 levels were measured within 24 h of admission. Local complications (acute peripancreatic fluid collection, acute necrotic collection, pseudocyst, and walled-off necrosis) were diagnosed by abdominal computed tomography. Cut-off for trypsinogen-2 level was assessed using receiver operating characteristic curve, and predictors of local complications were analyzed by logistic regression. RESULTS: Thirty-seven (25.7%) patients developed local complications. Urinary trypsinogen-2 levels were significantly higher in patients with local complications compared with those without local complications (median [interquartile range], 3210 [620-9764.4] µg/L vs 627.3 [72.3-5895] µg/L, P = 0.006). Urinary trypsinogen-2 significantly outperformed BISAP score in predicting local complications (area under the receiver operating characteristic curve 0.65 [95% CI: 0.55-0.75] vs 0.48 [95% CI: 0.38-0.58], P = 0.005). At the optimal cut-off of 500 µg/L, the sensitivity, specificity, positive predictive value, and negative predictive value of trypsinogen-2 level were 78.4%, 45.8%, 33.3%, and 86.0%, respectively. Urinary trypsinogen-2 level > 500 µg/L was an independent predictor of local complications (adjusted odds ratio, 3.72; 95% CI: 1.42-9.76; P = 0.007). By contrast, BISAP score ≥ 3 and pleural effusion predicted organ failure but not local complications. CONCLUSION: In a prospective cohort, urinary trypsinogen-2 level > 500 µg/L independently predicted local complications of AP.

Calycosin-7-O-ß-D-glucoside reduces myocardial injury in heat stroke rats.

BACKGROUND/PURPOSE: Calycosin-7-O-ß-D-glucoside (CG), a calycosin derivative compound derived from Astragali Radix, has protective effect against ischemia/reperfusion injury as well as bacterial endotoxin-induced vascular cell injury. In the present study, we ascertained whether CG could reduce myocardial injury in heatstroke rats. METHODS: Heat stroke was induced by exposing anaesthetized rats to heat stress (43 °C for 70 min). Rats were given an i.p. dose of CG (26.8 mg/ml/kg) or vehicle solution (ml/kg) 15 min before the start of heat stress and immediately after termination of heat stress. Left ventricular performance, myocardial injury markers in the blood, and myocardial damage scores were assessed in heat stroke rats treated with or without CG. Additionally, cardiac levels of oxidative stress and inflammatory status were estimated simultaneously. RESULTS: At the time point of heat stroke onset, compared with normothermic controls, group rats with vehicle solution had significantly decreased survival rate, increased hyperthermia, decreased left ventricular stress markers, and increased cardiac damage scores. Compared with group rats with vehicle solution, group rats with CG had significantly improved survival rate, decreased hyperthermia, decreased cardiac ischemic, inflammatory, and oxidative damage. CONCLUSION: We thus conclude that myocardial injury can be a pressing need for the design of diagnostic and therapeutic modalities for heat stroke. In particular, our data indicate that CG protects against heat stroke in rats by mitigating myocardial injury.

Role of Cancer Stem Cells in Cholangiocarcinoma and Therapeutic Implications.

Cholangiocarcinoma (CCA) is the second most common type of liver cancer, and is highly aggressive with very poor prognosis. CCA is classified into intrahepatic cholangiocarcinoma (iCCA) and extra-hepatic cholangiocarcinoma (eCCA), which is further stratified into perihilar (pCCA) and distal (dCCA). Cancer stem cells (CSCs) are a subpopulation of cancer cells capable of tumor initiation and malignant growth, and are also responsible for chemoresistance. Thus, CSCs play an important role in CCA carcinogenesis. Surface markers such as CD133, CD24, CD44, EpCAM, Sox2, CD49f, and CD117 are important for identifying and isolating CCA CSCs. CSCs are present in the tumor microenvironment (TME), termed 'CSC niche', where cellular components and soluble factors interact to promote tumor initiation. Epithelial-to-mesenchymal transition (EMT) is another important mechanism underlying carcinogenesis, involved in the invasiveness, metastasis and chemoresistance of cancer. It has been demonstrated that EMT plays a critical role in generating CSCs. Therapies targeting the surface markers and signaling pathways of CCA CSCs, proteins involved in TME, and immune checkpoint proteins are currently under investigation. Therefore, this review focuses on recent studies on the roles of CSCs in CCA; the possible therapeutic strategies targeting CSCs of CCA are also discussed.

Ultrasound-Guided Minimally Invasive Surgical Resection of Retrocalcaneal Bursitis: A Preliminary Comparison With Traditional Open Surgery.

Posterior heel pain is a common complaint that is often caused by overuse injuries. In such cases, the retrocalcaneal bursa is compressed and chafed repeatedly, leading to local inflammation. Sonography is a popular imaging tool used to study the pathology of soft tissues, and it can be used to assist in diagnosing bursitis because of its accuracy. Herein, we report an innovative method to treat retrocalcaneal bursitis under ultrasound guidance. Ten patients with posterior heel pain for >6 months who failed conservative treatment received this ultrasound-guided minimally invasive surgery. An endoscopic puncher and burr were inserted under ultrasound guidance via a stabbing wound, and the swollen retrocalcaneal bursa and bony prominence were resected. The patients were able to ambulate and undergo a rehabilitation program 2 weeks postoperatively. In the patients who underwent this ultrasound-guided minimally invasive surgery, both the average surgical time and average hospital stay were shorter than in those (n = 12) who underwent open surgery. In outcome rating assessment, the American Orthopaedic Foot & Ankle Society (AOFAS) pain score and total AOFAS ankle-hindfoot score were improved in the ultrasound-guided minimally invasive surgery group compared to the open surgery group at 2 months postoperatively. Other advantages included lesser wound pain, shorter hospital stay, faster recovery time, and minimal blood loss. Accordingly, ultrasound-guided surgery appears to be a good option for the treatment of retrocalcaneal bursitis.