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Abstract Background Topical tacrolimus has been used as one of the treatment options for atopic dermatitis (AD). A burning sensation is the most common side effect of topical tacrolimus. Objectives This study was designed to identify genetic variations and clinical features to predict burning sensation by topical tacrolimus in patients with AD. Methods Patients with AD who had applied topical tacrolimus were classified according to the presence of a burning sensation. We compared the patients' demographics and blood test results, including serum eosinophil, serum immunoglobulin E and multiple allergen simultaneous test. Furthermore, the frequency of variations in barrier‐ (KLK7, FLG 3321delA, FLG K4022X, SPINK5 1156, SPINK5 1188, SPINK5 2475) and immune response‐ (DEFB1, KDR, CDKAL1, IL‐5RA, IL‐9, IL‐12RB1, IL‐12RB2, IL‐17RA) related genes was compared between two groups by reverse blot hybridization assay of the buccal mucosa. Results Among 206 patients with AD using topical tacrolimus, 34 (16.5%) complained of a burning sensation. The burning sensation was associated with severe AD and a family history of atopic disease. Furthermore, with statistical significance, a heterozygous mutation in the filaggrin gene (FLG K4022X) was more frequent in AD patients with a burning sensation due to topical tacrolimus. However, no other significant genetic differences were observed between them. Conclusions A burning sensation caused by topical tacrolimus can be expected in AD patients with severe symptoms, a family history of atopy and a genetic variation such as FLG K4022X.

Purpose Ejection fraction, measured as the fraction of blood ejected from the ventricle in each heartbeat using M-mode echocardiography, serves as a primary indicator of left ventricular systolic function. This study explores the correlation between blood pressure and left ventricular systolic function in neonates using M-mode echocardiography. Methods Neonates who underwent echocardiography in the neonatal intensive care unit between January 2011 and December 2020 were retrospectively studied. Results Our analyses showed a significant association between ejection fraction and systolic blood pressure, but not with diastolic or mean blood pressure—both of which are more sensitive to hypotension. Ejection fraction was also not significantly associated with heart rate, urine output, or inotropic support in this study, suggesting that factors influencing urine output may not directly relate to ejection fraction. Additionally, we found that higher systolic blood pressure was correlated with advanced gestational age, the absence of patent ductus arteriosus, and no need for fentanyl administration. Notably, lower gestational age and lack of mechanical ventilation were both associated with increased hourly urine output, suggesting that developmental maturity and respiratory stability may influence renal function. Conclusion Neonatal hypotension occurred secondary to decreased systolic cardiac function and peripheral vascular resistance. Neonatologists should carefully monitor the individual components of blood pressure and prescribe medications accordingly, considering that systolic blood pressure is correlated with ejection function.

Background: This study examines the association between perceived age discrimination and depression among South Korean older adults and whether regular exercise can moderate this association. There has been a noticeable rise in ageism in both the media and the society during and following the COVID-19 pandemic. Perceived age discrimination can lead to an internalization of ageist attitudes and stereotypes, resulting in decreased self-efficacy and increased negative emotions, which negatively impact on the health of older adults. While regular exercise has been shown to boost self-esteem and enhance positive self-perceptions of aging, its potential as an intervention against the psychological impact of age discrimination is under-explored. Methods: Using data from 9,920 participants (aged 65+) in the 2020 National Survey of Older Koreans, depression was regressed on age discrimination controlling for age, gender, education, marital status, self-rated health, employment status, and activities of daily living (ADLs). A hierarchical multiple regression analysis was employed to examine the moderating effect of exercise. Results: Higher levels of perceived age discrimination were directly associated with higher levels of depression. Regular exercise significantly moderated this relationship, reducing the negative impact of perceived age discrimination on depressive symptoms. Conclusions: Considering the rise of ageism in South Korea, regular exercise can serve as an important mechanism for combating ageism by effectively managing stress and enhancing self-resilience. Our findings highlight the importance of promoting exercise as a potential strategy to mitigate the detrimental mental health effects of age discrimination, particularly in the post-pandemic era.

Background Ibuprofen and acetaminophen are widely used as adjuvant analgesics for postoperative pain. This meta-analysis compared the effects of intravenous (IV) ibuprofen and acetaminophen on postoperative opioid consumption and pain intensity after general anesthesia. Methods PubMed/MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to May 2023. Randomized controlled trials comparing the effects of perioperative IV ibuprofen and acetaminophen on postoperative opioid consumption and pain after general anesthesia were included in the meta-analysis and trial sequential analysis (TSA). Results Eight studies with 494 participants were included. Compared to IV acetaminophen, IV ibuprofen significantly reduced 24 h opioid consumption, presented as morphine equivalents (mean difference [MD]: –6.01 mg, 95% CI [–8.60, –3.42], P < 0.00001, I2 = 55%), and pain scores (on a scale of 0–10) at 4–6 h (MD: –0.83, 95% CI [–1.29, –0.37], P = 0.0004, I2 = 65%) and 12 h (MD: –0.38, 95% CI [–0.68, –0.08], P = 0.01, I2 = 11%) postoperatively. These results were statistically significant in TSA. Pain scores at 24 h postoperatively and side effects were not significantly different between the two groups in the meta-analysis, and TSA revealed that the sample size was too small to adequately evaluate the effects, requiring further studies for conclusive results. Conclusions Perioperative IV ibuprofen reduced 24 h opioid consumption and pain severity up to 12 h postoperatively compared to acetaminophen. Additional research is required to assess pain intensity beyond 12 h and side effects.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with significant morbidity, including pruritus, recurrent skin lesions, and immune dysregulation. This study aimed to investigate the antioxidative and anti-AD effects of peptides derived from hydrolyzed Sebastes schlegelii (Korea rockfish) tail by-products. Hydrolysates were prepared using various enzymes, including Alcalase, Flavourzyme, Neutrase, and Protamex. Among them, Protamex hydrolysates demonstrated the highest ABTS radical scavenging activity with an RC50 value of 69.69 ± 0.41 µg/mL. Peptides were further isolated from the Protamex hydrolysate using dialysis, fast protein liquid chromatography (FPLC), and high-performance liquid chromatography (HPLC). The most active peptide, STPO-B-II, exhibited a single peak and was identified as a sequence of Glu-Leu-Ala-Lys-Thr-Trp-His-Asp-Met-Lys, designated as MP003. In vivo experiments were conducted using a 2,4-dinitrochlorbenzene (DNCB)-induced AD model in NC/Nga mice. The isolated peptide, MP003, showed significantly reduced AD symptoms, including erythema, lichenification, and collagen deposition. Additionally, MP003 decreased epidermal and dermal thickness, eosinophil, and mast cell infiltration and downregulated the expression of pro-inflammatory cytokines IL-1β, IL-6, and IgE in serum and skin tissues. These findings suggest that peptides derived from Sebastes schlegelii tail by-products may serve as potential therapeutic agents for AD.

Randomized controlled trials (RCTs) are considered the most rigorous study design for testing hypotheses and the gold standard for evaluating intervention effectiveness. However, RCTs are often conducted under the assumption of ideal conditions that may differ from real-world scenarios in which various issues, such as loss to follow-up, mistakes in participant enrollment or intervention, and low subject compliance or adherence, may occur. There are various group-defining strategies for analyzing RCT data, including the intention-to-treat (ITT), as-treated, and per-protocol (PP) approaches. The ITT principle involves analyzing all participants according to their initial group assignments, regardless of study completion and compliance or adherence to treatment protocols. This approach aims to replicate real-world clinical settings in which several anticipated or unexpected conditions may occur with regard to the study protocol. For the PP approach, only participants who meet the inclusion criteria, complete the interventions according to the study protocols, and have primary outcome data available are included. This approach aims to confirm treatment effects under optimal conditions. In general, the ITT principle is preferred for superiority and inequality trials, whereas the PP approach is preferred for equivalence and non-inferiority trials. However, both analytical approaches should be conducted and their results compared to determine whether significant differences exist. Overall, using both the ITT and PP approaches can provide a more complete picture of the treatment effects and ensure the reliability of the trial results.

Abstract Background Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods A multicenter randomized phase II trial involving 364 patients with LARC (cT3–4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45–50.4 Gy in 25–28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2–5 weeks from the last cycle of chemotherapy in the experimental arm and 6–8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

The skin is vulnerable to damage from ultraviolet rays and oxidative stress, which can lead to aging and pigmentation issues. This study investigates the antioxidant and whitening efficacy of a decapeptide (DP, KGYSSYICDK) derived from marine fish by-products and evaluates its potential as a new skin-whitening agent. DP demonstrated high antioxidant activity, showing comparable or superior performance to Vitamin C (Vit. C) in ferric reducing antioxidant power (FRAP) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. In hydrogen peroxide (H2O2)-treated HaCaT cells, DP increased cell viability and reduced reactive oxygen species (ROS) generation. Furthermore, DP inhibited tyrosinase activity and decreased melanin production in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 melanoma cells in a dose-dependent manner. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that DP reduces the mRNA expression of MITF, tyrosinase, and MC1R, thus suppressing melanin production. DP exhibits strong binding interactions with multiple amino acid residues of tyrosinase, indicating potent inhibitory effects on the enzyme. These results suggest that DP possesses significant antioxidant and whitening properties, highlighting its potential as a skin-whitening agent. Future research should focus on optimizing DP’s structure and exploring structure–activity relationships.

Peptides, composed of 2–50 amino acids, have gained attention in anti-aging treatments due to their high safety, low irritation, and cost-effective production. This study aimed to evaluate the anti-wrinkle efficacy of Tetrapeptide-68, derived from the skin structural protein Loricrin, on periorbital wrinkles in women aged 30–65 years. A 12-week, double-blind, randomized controlled trial was conducted with 25 participants who applied the Tetrapeptide-68 (100 ppm) O/W formulation around the eyes. Skin physiological parameters were assessed at baseline, 4, 8, and 12 weeks. Participants also completed efficacy and usability questionnaires. Significant improvements in wrinkle reduction were observed with Tetrapeptide-68 cream treatment, as measured by various skin roughness parameters and 3D imaging analysis. Participants reported positive changes in skin texture and moisture levels, with no adverse reactions noted. Tetrapeptide-68 cream demonstrates promising anti-wrinkle effects, highlighting its potential as an effective ingredient in anti-aging skincare formulations. Further studies are recommended to explore its long-term benefits and underlying mechanisms.

BackgroundThe aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section.MethodsFifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery.ResultsNo significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 μg [interquartile range, 291.3-507.8 μg versus 428.0 μg [interquartile range, 305.0-507.0 μg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes.ConclusionProphylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section.

Study Design Retrospective observational study. Purpose This study aimed to investigate the impact of plating on postoperative serial segmental motion and its correlation with clinical outcomes in single-level anterior cervical discectomy and fusion (ACDF) for up to 1 year. Overview of Literature The advantages and disadvantages of using cervical plating in ACDF have been well discussed; however, few studies compared the early serial segmental motions at the postoperative level between plating and non-plating. Methods In retrospectively collected data, 149 patients who underwent single-level ACDF for degenerative disease were enrolled and divided into non-plating (n=66) and plating (n=83). Interspinous motion (ISM) at the arthrodesis segment, Numeric Rating Scale (NRS) for neck pain, and Neck Disability Index (NDI) were serially evaluated at 3, 6, and 12 months postoperatively. Predictable factors for fusion, including age, sex, plating, diabetes, smoking, and type of grafts, were investigated, and fusion was defined as ISM

Preprints are preliminary research reports that have not yet been peer-reviewed. They have been widely adopted to promote the timely dissemination of research across many scientific fields. In August 1991, Paul Ginsparg launched an electronic bulletin board intended to serve a few hundred colleagues working in a subfield of theoretical high-energy physics, thus launching arXiv, the first and largest preprint platform. Additional preprint servers have since been implemented in different academic fields, such as BioRxiv (2013, Biology; www.biorxiv.org) and medRxiv (2019, Health Science; www.medrxiv.org). While preprint availability has made valuable research resources accessible to the general public, thus bridging the gap between academic and non-academic audiences, it has also facilitated the spread of unsupported conclusions through various media channels. Issues surrounding the preprint policies of a journal must be addressed, ultimately, by editors and include the acceptance of preprint manuscripts, allowing the citation of preprints, maintaining a double-blind peer review process, changes to the preprint’s content and authors’ list, scoop priorities, commenting on preprints, and preventing the influence of social media. Editors must be able to deal with these issues adequately, to maintain the scientific integrity of their journal. In this review, the history, current status, and strengths and weaknesses of preprints as well as ongoing concerns regarding journal articles with preprints are discussed. An optimal approach to preprints is suggested for editorial board members, authors, and researchers.

Abstract Insulin and insulin-like growth factor 1 (IGF-1) signaling regulate cellular growth and glucose metabolism in the myocardium. However, their physiological role in the cells of the cardiac conduction system has never been explored. Therefore, we sought to determine the spatiotemporal function of insulin/IGF-1 receptors in the sinoatrial node (SAN). We generated cardiac conduction cell-specific inducible IGF-1 receptor (IGF-1R) knockout (KO) (CSIGF1RKO), insulin receptor (IR) KO (CSIRKO), and IR/IGF-1R double-KO (CSDIRKO) mice and evaluated their phenotypes. Telemetric electrocardiography revealed regular sinus rhythm in CSIGF1RKO mice, indicating that IGF-1R is dispensable for normal pacemaking. In contrast, CSIRKO and CSDIRKO mice exhibited profound sinus bradycardia. CSDIRKO mice showed typical sinus node dysfunction characterized by junctional rhythm and sinus pauses on electrocardiography. Interestingly, the lack of an insulin receptor in the SAN cells of CSIRKO and CSDIRKO mice caused sinus nodal fibrosis. Mechanistically, hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) protein expression significantly decreased in the CSIRKO and CSDIRKO mice relative to the controls. A patch-clamp study of the SAN cells of CSIRKO mice revealed a significant decrease in the funny current, which is responsible for spontaneous diastolic depolarization in the SAN. This result suggested that insulin receptor loss reduces the heart rate via downregulation of the HCN4 channel. Additionally, HCN1 expression was decreased in CSDIRKO mice, explaining their sinus node dysfunction. Our results reveal a previously unrecognized role of insulin/IGF-1 signaling in sinus node structural maintenance and pacemaker function.

Preprints are preliminary research reports that have not yet been peer-reviewed. They have been widely adopted to promote the timely dissemination of research across many scientific fields. In August 1991, Paul Ginsparg launched an electronic bulletin board intended to serve a few hundred colleagues working in a subfield of theoretical high-energy physics, thus launching arXiv, the first and largest preprint platform. Additional preprint servers have since been implemented in different academic fields, such as BioRxiv (2013, Biology; www.biorxiv.org) and medRxiv (2019, Health Science; www.medrxiv.org). While preprint availability has made valuable research resources accessible to the general public, thus bridging the gap between academic and non-academic audiences, it has also facilitated the spread of unsupported conclusions through various media channels. Issues surrounding the preprint policies of a journal must be addressed, ultimately, by editors and include the acceptance of preprint manuscripts, allowing the citation of preprints, maintaining a double-blind peer review process, changes to the preprint’s content and authors’ list, scoop priorities, commenting on preprints, and preventing the influence of social media. Editors must be able to deal with these issues adequately, to maintain the scientific integrity of their journal. In this review, the history, current status, and strengths and weaknesses of preprints as well as ongoing concerns regarding journal articles with preprints are discussed. An optimal approach to preprints is suggested for editorial board members, authors, and researchers.

Background The application of a heated-humidified breathing circuit (HHBC) may reduce respiratory heat loss during mechanical ventilation, but its effect in preventing intraoperative hypothermia is controversial. This study aimed to investigate the effectiveness of HHBC in maintaining the core temperature of patients receiving mechanical ventilation under general anesthesia. Methods We searched MEDLINE, Embase, Cochrane library (CENTRAL), and Google Scholar to identify all randomized controlled trials (RCTs) up to February 2022 that compared the intraoperative core temperature in patients with heated humidifier (HH) and other circuit devices. The primary outcome was the intraoperative core temperature at the end of surgery. The weighted mean differences (WMDs) between the groups and their 95% CIs were calculated for each outcome. We performed a trial sequential analysis of the primary outcomes to assess whether our results were conclusive. Results Eighteen RCTs with 993 patients were included in the analysis. A significantly higher core temperature was observed at the end of surgery in patients with HH than those with no device (WMD = 0.734, 95% CI [0.443, 1.025]) or heat and moisture exchanger (WMD = 0.368, 95% CI [0.118, 0.618]), but with substantial heterogeneity. Conclusions Although HHBC did not absolutely prevent hypothermia, this meta-analysis suggests that it can be used as an effective supplemental device to maintain the intraoperative core temperature under general anesthesia. However, considering the substantial heterogeneity and limitations of this study, further well-designed studies are needed to clarify the effectiveness of HHBC.

In this study, we investigated the enhanced anti-inflammatory activity and the effects on non-alcoholic fatty liver disease (NAFLD) of fermented Fagopyrum tataricum (F. tataricum) Gaertner extract (FFT) through in vitro analysis. We utilized high-performance liquid chromatography (HPLC) to analyze the non-fermented F. tataricum Gaertner extract (NFT) and the marker components, rutin and quercetin in FFT, to confirm changes in composition due to fermentation. The anti-inflammatory activity of NFT and FFT was evaluated using a lipopolysaccharide (LPS)-induced RAW 264.7 cell inflammation model. Simultaneously, the NAFLD improvement effects were measured by evaluating lipid accumulation and the expression of lipid synthesis regulators in free fatty acid (FFA)-induced HepG2 cells. HPLC analysis confirmed an increase in rutin content after the fermentation of F. tataricum Gaertner. Upon treatment with NFT and FFT at a concentration of 400 μg/mL, LPS-induced nitric oxide (NO) production values in RAW 264.7 cells were reduced to 16.12 μM and 2.09 μM, respectively, indicating enhanced significant inhibition (p < 0.05) of NO production through fermentation. FFT demonstrated the significant inhibition (p < 0.05) of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein, and inflammatory cytokine mRNA expression through the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in LPS-induced RAW 264.7 cells. In FFA-induced HepG2 cells, FFT significant suppressed (p < 0.05) lipid accumulation and the expression of sterol regulatory element binding protein (SREBP)-1c, CCAAT/enhancer binding protein (C/EBP)α proteins, and acetyl-CoA carboxylase (ACC) mRNA. The results of this study suggest the potential utilization of FFT as a material for improving NAFLD.

This study investigated the antioxidant, antimicrobial, and anti-atopic dermatitis (AD) effects of a novel peptide (CP) derived from a Chromis notata by-product hydrolysate. Alcalase, Flavourzyme, Neutrase, and Protamex enzymes were used to hydrolyze the C. notata by-product protein, and the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging activity was measured. Alcalase hydrolysate exhibited the highest ABTS radical-scavenging activity, leading to the selection of Alcalase for further purification. The CHAO-1-I fraction, with the highest ABTS activity, was isolated and further purified, resulting in the identification of the peptide CP with the amino acid sequence Ala-Gln-Val-Met-Lys-Leu-Pro-His-Arg-Met-Gln-His-Ser-Gln-Ser. CP demonstrated antimicrobial activity against Staphylococcus aureus, inhibiting its growth. In a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin model in mice, CP significantly alleviated skin lesions, reduced epidermal and dermal thickness, and inhibited mast cell infiltration. Moreover, CP suppressed the elevated levels of interleukin-6 (IL-6) in the plasma of DNCB-induced mice. These findings highlight the potential of CP as a therapeutic agent for AD and suggest a novel application of this C. notata by-product in the fish processing industry.

Tables and figures are commonly adopted methods for presenting specific data or statistical analysis results. Figures can be used to display characteristics and distributions of data, allowing for intuitive understanding through visualization and thus making it easier to interpret the statistical results. To maximize the positive aspects of figure presentation and increase the accuracy of the content, in this article, the authors will describe how to choose an appropriate figure type and the necessary components to include. Additionally, this article includes examples of figures that are commonly used in research and their essential components using virtual data.

Background/Aims Different modalities have been employed to reduce the risk and severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, there has been a paucity of studies comparing the efficacy of various prophylactic modalities for preventing PEP. This network meta-analysis (NMA) aimed to determine the relative efficacy of pancreatic duct stents and pharmacological modalities for preventing PEP. Methods We performed a systematic and comprehensive search to identify and analyze all randomized controlled studies published until June 2020 that examined the effectiveness of pancreatic duct stents, rectal non-steroidal anti-inflammatory drugs (NSAIDs) based regimens, hydration, and their combinations for the prevention of PEP. The primary outcome was the frequency of PEP. An NMA was performed to combine direct and indirect comparisons of different prophylactic modalities. Results The NMA included 46 studies evaluating 18 regimens in 16,241 patients. Based on integral analysis of predictive interval plots, and expected mean ranking and surface under the cumulative ranking curve values, combination prophylaxis with indomethacin + lactated Ringer’s solution (LR), followed by diclofenac + nitrate and indomethacin + normal saline, was found to be the most efficacious modality for the overall prevention of PEP. Indomethacin + LR, followed by diclofenac and pancreatic duct stents, was the most efficacious modality for high-risk groups. Conclusions Rectal NSAIDs-based combination regimens with aggressive hydration or nitrate are superior to single modalities for the prevention of PEP.

Abstract Background Rubus occidentalis, also known as black raspberry, contains several bioactive components that vary depending on the maturity of the fruit. The goal of this study was to evaluate the efficacy of immature Rubus occidentalis extract(iROE) on acid-induced hyperalgesia, investigate the mechanism involved, and compare the antihyperalgesic effect of immature and mature ROEs. Methods In adult male Sprague-Dawley rats, chronic muscle pain was induced via two injections of acidic saline into one gastrocnemius muscle. To evaluate the dose response, the rats were injected intraperitoneally with 0.9% saline or iROE (10, 30, 100, or 300 mg/kg) following hyperalgesia development. To evaluate the mechanism underlying iROE-induced analgesia, the rats were injected intraperitoneally with saline, yohimbine 2 mg/kg, dexmedetomidine 50 μg/kg, prazosin 1 mg/kg, atropine 5 mg/kg, mecamylamine 1 mg/kg, or naloxone 5 mg/kg 24 h after hyperalgesia development, followed by iROE 300 mg/kg administration. To compare immature versus mature ROE, the rats were injected with mature ROE 300 mg/kg and immature ROE 300 mg/kg after hyperalgesia development. For all experiments, the mechanical withdrawal threshold(MWT) was evaluated using von Frey filaments before the first acidic saline injection, 24 h after the second injection, and at various time points after drug administration. Data were analysed using multivariate analysis of variance(MANOVA) and the linear mixed-effects model(LMEM). We compared the MWT at each time point using analysis of variance with the Bonferroni correction. Results The iROE 300 mg/kg injection resulted in a significant increase in MWT compared with the control, iROE 30 mg/kg, and iROE 100 mg/kg injections at ipsilateral and contralateral sites. The iROE injection together with yohimbine, mecamylamine, or naloxone significantly decreased the MWT compared with iROE alone, whereas ROE together with dexmedetomidine significantly increased the MWT. According to MANOVA, the effects of immature and mature ROEs were not significantly different; however, the LMEM presented a significant difference between the two groups. Conclusions Immature R. occidentalis showed antihyperalgesic activity against acid-induced chronic muscle pain, which may be mediated by the α2-adrenergic, nicotinic cholinergic, and opioid receptors. The iROE displayed superior tendency regarding analgesic effect compared to mature ROE.

This study explores the potential of a natural composite formulation known as ED, consisting of Ecklonia cava (E. cava, family: Lessoniaceae) and Chrysanthemum indicum Linne (C. indicum, family: Asteraceae), in alleviating lung inflammation induced by fine particulate matter (PM2.5). Initial assessments confirmed that neither ED nor one of its components, dieckol, exhibited cytotoxic effects on A549 cells. Subsequently, the impact of ED and dieckol on MUC5AC gene expression in A549 cells stimulated by phorbol 12-myristate 13-acetate (PMA) was investigated, revealing promising results that demonstrated a dose-dependent inhibition of MUC5AC gene expression. The study also delves into the underlying mechanisms, demonstrating that ED and dieckol effectively suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including JNK, ERK, and p38, which are known to be involved in the regulation of MUC5AC gene expression. In in vivo experiments using a PM2.5-induced pulmonary inflammation mouse model, the research findings showed that ED mitigated cellular accumulation in the airways, leading to a significant reduction in the total cell count in bronchoalveolar lavage fluid (BALF). Moreover, ED exhibited protective effects against PM2.5-induced pulmonary damage, characterized by reduced inflammatory cell infiltration and decreased mucus secretion in pulmonary tissues. Additionally, ED’s anti-inflammatory properties were evident in its ability to decrease the levels of key inflammatory cytokines, TNF-α and IL-6, both in the serum and lung tissue of the PM2.5-induced pulmonary inflammation mouse model. These findings suggest the potential of ED as a therapeutic agent for inflammatory respiratory diseases.

Most diseases have more than two interventions or treatment methods, and the application of network meta-analysis (NMA) studies to compare and evaluate the superiority of each intervention or treatment method is increasing. Understanding the concepts and processes of systematic reviews and meta-analyses is essential to understanding NMA. As with systematic reviews and meta-analyses, NMA involves specifying the topic, searching for and selecting all related studies, and extracting data from the selected studies. To evaluate the effects of each treatment, NMA compares and analyzes three or more interventions or treatment methods using both direct and indirect evidence. There is a possibility of several biases when performing NMA. Therefore, key assumptions like similarity, transitivity, and consistency should be satisfied when performing NMA. Among these key assumptions, consistency can be evaluated and quantified by statistical tests. This review aims to introduce the concepts of NMA, analysis methods, and interpretation and presentation of the results of NMA. It also briefly introduces the emerging issues in NMA, including methods for evaluation of consistency.

Background Nasotracheal intubation is generally performed for intraoral surgery. Case A 34-year-old female patient who underwent orthognathic surgery exhibited repeated endotracheal tube cuff tears during nasotracheal intubation. After intubation, leaks developed, and torn endotracheal cuff was observed in the removed endotracheal tube. Subsequently, re-intubation through the same nasal cavity was performed immediately, but leakage from the torn endotracheal tube cuff was re-observed. A leakage test of the extubated tube revealed air bubbles and leaks near the tube cuff due to the tear. Nasotracheal intubation was performed through the other nasal cavity, and there were no leakage findings or abnormalities. During the course of the surgery, the surgeon noticed that the orthodontic micro-implant deposited in the mid-tube cavity was exposed to the nasal cavity. Conclusions We aimed to emphasize caution and discuss the possibility that orthodontic micro-implants that are not confirmed during preoperative evaluation may cause repeated endotracheal tube cuff tears.