Study on the Therapeutic Effects and Mechanisms of Gintonin in Irritable Bowel Syndrome and Its Relationship with TRPV1, TRPV4, and NaV1.5.

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action of gintonin in IBS, we developed a zymosan-induced IBS murine model. In addition, electrophysiological experiments were conducted to confirm the relevance of various ion channels. In mice, gintonin restored colon length and weight to normal and decreased stool scores, whilst food intake remained constant. Colon mucosal thickness and inflammation-related tumor necrosis factor-α levels were decreased by gintonin, along with a reduction in pain-related behaviors. In addition, the fecal microbiota from gintonin-treated mice had relatively more Lactobacillaceae and Lachnospiraceae and less Bacteroidaceae than microbiota from the control mice. Moreover, gintonin inhibited transient receptor potential vanilloid (TRPV) 1 and TRPV4 associated with visceral hypersensitivity and voltage-gated Na+ 1.5 channels associated with GI function. These results suggest that gintonin may be one of the effective components in the treatment of IBS.

Interphase-Controlled Inkjet Printing of MicroInlaid OLEDs: Effects of Solvent- and Solute-Polymer Interactions.

Inkjet printing, a highly promising technique for the cost-effective fabrication of large-scale organic light-emitting devices (OLEDs), typically necessitates the intricate alignment of precisely patterned insulating layers. Recently, we introduced a unique single-step inkjet printing process that produces well-patterned microinlaid spots of functional compounds through insulating polymer layers. This approach exploits lateral phase separation between the solute of functional compounds and the polymer, allowing the simultaneous spatial etching of the polymer and the infilling of the solute using a single inkjet-printed sessile droplet. Here, we demonstrate that the interaction between the solvent and polymer, as well as the solute and polymer, critically determines the precision and efficiency of printing. This is particularly evident when using either the insulating poly(vinylpyridine) isomer of poly(4-vinylpyridine) (P4VP) or poly(2-vinylpyridine) (P2VP) with chloroform as a solvent, which allows for a detailed examination of these interactions based on certain solubility parameters. Micro-Raman spectroscopy reveals that the self-organizing capability of the microinlaid spots with P4VP is superior to that with P2VP. This is due to the fact that P2VP shows higher affinity to the solvent and causes imperfect phase separation as compared to P4VP. As a result, a performance evaluation demonstrates enhanced device performance for inkjet-printed green micro-OLEDs with P4VP, exhibiting a higher external quantum efficiency of 3.3% compared to that of 2.3% achieved with P2VP. These findings elucidate the important roles of solvent-polymer and solute-polymer interactions in the inkjet printing process, leading to interfacial control of inkjet printing technique for the cost-effective production of high-performance and high-resolution micro-OLEDs.

Effect of herbal medicine on postoperative nausea and vomiting after laparoscopic surgery: A systematic review and meta-analysis.

BACKGROUND: Traditionally, herbal medicines have been used to alleviate nausea and vomiting; however, a comprehensive clinical evaluation for postoperative nausea and vomiting (PONV), especially after laparoscopic surgery, remains limited. This review aimed to evaluate the efficacy and safety of herbal medicine as an alternative therapy to prevent and manage nausea and vomiting after laparoscopic surgery compared with untreated, placebo, and Western medicine groups. METHODS: We searched 11 databases, including EMBASE, PubMed, and the Cochrane Library, to collect randomized controlled trials (RCTs) of herbal medicines on PONV after laparoscopic surgery on July 7, 2022. Two independent reviewers screened and selected eligible studies, extracted clinical data, and evaluated the quality of evidence using the Cochrane risk-of-bias tool. The primary outcome was the incidence of PONV, whereas the secondary outcomes included the frequency and intensity of PONV, symptom improvement time, antiemetic requirement frequency, and incidence of adverse events. Review Manager Version 5.3. was used for the meta-analysis. RESULTS: We identified 19 RCTs with 2726 participants comparing herbal medicine with no treatment, placebo, and Western medicine. The findings showed that compared with no treatment, herbal medicine demonstrated significant effects on vomiting incidence (risk ratio [RR] = 0.43, 95% confidence interval [CI] 0.32-0.57, P < .00001). Compared with placebo, herbal medicine revealed a significant effect on the severity of nausea 12 hours after laparoscopic surgery (standardized mean difference = -2.04, 95% CI -3.67 to -0.41, P = .01). Herbal medicines showed similar effects with Western medicine on the incidence of postoperative nausea (RR = 0.94, 95% CI 0.63-1.42, P = .77) and vomiting (RR = 0.68, 95% CI 0.25-1.84, P = .45). Furthermore, comparing the experimental group containing herbal medicine and control group excluding herbal medicine, adverse events were considerably lower in the group with herbal medicine (RR = 0.45, 95% CI 0.27-0.72, P = .001). CONCLUSION: Herbal medicine is an effective and safe treatment for nausea and vomiting secondary to laparoscopic surgery. However, the number of studies was small and their quality was not high; thus, more well-designed RCTs are warranted in the future.

A Bayesian convolutional neural network-based generalized linear model.

Convolutional neural networks (CNNs) provide flexible function approximations for a wide variety of applications when the input variables are in the form of images or spatial data. Although CNNs often outperform traditional statistical models in prediction accuracy, statistical inference, such as estimating the effects of covariates and quantifying the prediction uncertainty, is not trivial due to the highly complicated model structure and overparameterization. To address this challenge, we propose a new Bayesian approach by embedding CNNs within the generalized linear models (GLMs) framework. We use extracted nodes from the last hidden layer of CNN with Monte Carlo (MC) dropout as informative covariates in GLM. This improves accuracy in prediction and regression coefficient inference, allowing for the interpretation of coefficients and uncertainty quantification. By fitting ensemble GLMs across multiple realizations from MC dropout, we can account for uncertainties in extracting the features. We apply our methods to biological and epidemiological problems, which have both high-dimensional correlated inputs and vector covariates. Specifically, we consider malaria incidence data, brain tumor image data, and fMRI data. By extracting information from correlated inputs, the proposed method can provide an interpretable Bayesian analysis. The algorithm can be broadly applicable to image regressions or correlated data analysis by enabling accurate Bayesian inference quickly.

GRP78 blockade overcomes acquired resistance to EGFR-tyrosine kinase inhibitors in non-small cell lung cancer.

AIMS: While significant upregulation of GRP78 has been documented in lung cancer patients, its association with resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) remains underexamined. Our study aimed to elucidate the functional importance of GRP78 in acquired resistance to EGFR-TKIs in non-small cell lung cancer (NSCLC) and to evaluate its potential as a therapeutic target. MAIN METHODS: Immunoblot analysis or flow cytometry was employed to assess several markers for endoplasmic reticulum (ER) stress and apoptosis. Ru(II) complex I and HA15, two known GRP78 inhibitors, were used to evaluate the functional role of GRP78. A Xenograft assay was performed to evaluate the in vivo anti-cancer effects of the GRP78 inhibitors. KEY FINDINGS: We validated a significant increase in GRP78 protein levels in HCC827-GR, H1993-GR, and H1993-ER cells. The EGFR-TKI-resistant cells overexpressing GRP78 exhibited significantly higher cell proliferation rates than did their parental counterparts. Notably, GRP78 inhibition resulted in a more profound anti-proliferative and apoptotic response via heightened ER stress and subsequent reactive oxygen species (ROS) production in EGFR-TKI-resistant cell lines compared with their parental cells. In xenograft models implanted with HCC827-GR, both Ru(II) complex I and HA15 significantly suppressed tumor growth and reduced tumor weight. Additionally, we confirmed that GRP78 plays a critical role in the proliferation of H1975, an EGFR-TKI-resistant T790M-mutant cell line, relative to other NSCLC cell lines. SIGNIFICANCE: Our findings strongly support targeting of GRP78 as a promising therapeutic strategy for NSCLC patients with acquired resistance to EGFR-TKIs.

Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

Influence of Feeding Time on a Non-steroidal Anti-inflammatory Drug-induced Small Intestinal Injury Mouse Model.

BACKGROUND/AIM: Non-steroidal anti-inflammatory drugs (NSAIDs), the most widely used pharmaceuticals, induce various adverse effects, including gastrointestinal injuries, such as ulcers and bleeding. Animal models of NSAID-induced small intestinal injury (NSI) have been extensively employed for the development of preventive and therapeutic agents. However, some experimental variations related to feeding times have been observed following NSI induction. This study aimed to investigate the impact of feeding time on an NSI mouse model. MATERIALS AND METHODS: The mice were divided into eight groups: normal, sham, and model groups (with feeding times of 2 h, 6 h, 10 h, 14 h, 18 h, and 22 h; n=10 in each group). The mice were fasted for 18 h before the injection of indomethacin (15 mg/kg, subcutaneously), except for the normal group. Food supply was halted at specific time points (2 h, 6 h, 10 h, 14 h, 18 h, and 22 h); however, the normal and sham groups were continuously fed throughout the experiment. The length of the small intestine was measured, and histological analysis was performed 24 h after induction. RESULTS: Up to 14 h after induction, NSI, indicated by small intestine shortening, remained consistent, with a reduction in length of approximately 10-20%. However, feeding for more than 14 h significantly exacerbated NSI, both anatomically and histologically. CONCLUSION: The ulcerative changes observed in the small intestine 14 h after indomethacin injection may be closely associated with the influence of food on NSI.

Therapeutic strategy using novel RET/YES1 dual-target inhibitor in lung cancer.

Lung cancer represents a significant global health concern and stands as the leading cause of cancer-related mortality worldwide. The identification of specific genomic alterations such as EGFR and KRAS in lung cancer has paved the way for the development of targeted therapies. While targeted therapies for lung cancer exhibiting EGFR, MET and ALK mutations have been well-established, the options for RET mutations remain limited. Importantly, RET mutations have been found to be mutually exclusive from other genomic mutations and to be related with high incidences of brain metastasis. Given these facts, it is imperative to explore the development of RET-targeting therapies and to elucidate the mechanisms underlying metastasis in RET-expressing lung cancer cells. In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer.

Influence of patient-clinician relationship style on acupuncture outcomes in functional dyspepsia: A multi-site randomized controlled trial in Korea.

INTRODUCTION: Research suggests that a warm and empathic "patient-centered" patient-clinician relationship produces better clinical outcomes when compared with a more neutral "disease-centered" relationship. Acupuncturists performed both styles of therapy for patients with functional dyspepsia in Korea. METHODS: The present randomized controlled trial assigned patients (n = 73) to identical acupuncture treatment with either patient-centered augmented care or disease-centered limited care. The Korean version of the Nepean Dyspepsia Index (NDI-K) was the primary outcome measure. Secondary outcome measures included Consultation And Relational Empathy (CARE) scale. RESULTS: Both groups showed improvement in NDI-K. Patient-centered augmented acupuncture produced less effective symptom improvement compared to disease-centered limited acupuncture (NDI-K sum score and frequency; P = 0.008 and P = 0.037 respectively). CARE scores were higher for the augmented versus limited group (P = 0.001), supporting the fidelity of the experimentally controlled patient/clinician relationship. There were no significant differences between the groups in any of other secondary outcomes. CONCLUSION: Patients demonstrated greater improvement following acupuncture conducted with a more neutral, "disease-centered" style of relationship. This result is counter to similar research conducted in Western countries and suggests that cultural factors can significantly shape optimum styles of acupuncture therapy. PRACTICE IMPLICATIONS: Clinicians should consider cultural differences when applying acupuncture therapy.

Screening obstructive sleep apnea patients via deep learning of knowledge distillation in the lateral cephalogram.

The lateral cephalogram in orthodontics is a valuable screening tool on undetected obstructive sleep apnea (OSA), which can lead to consequences of severe systematic disease. We hypothesized that a deep learning-based classifier might be able to differentiate OSA as anatomical features in lateral cephalogram. Moreover, since the imaging devices used by each hospital could be different, there is a need to overcome modality difference of radiography. Therefore, we proposed a deep learning model with knowledge distillation to classify patients into OSA and non-OSA groups using the lateral cephalogram and to overcome modality differences simultaneously. Lateral cephalograms of 500 OSA patients and 498 non-OSA patients from two different devices were included. ResNet-50 and ResNet-50 with a feature-based knowledge distillation models were trained and their performances of classification were compared. Through the knowledge distillation, area under receiver operating characteristic curve analysis and gradient-weighted class activation mapping of knowledge distillation model exhibits high performance without being deceived by features caused by modality differences. By checking the probability values predicting OSA, an improvement in overcoming the modality differences was observed, which could be applied in the actual clinical situation.

Orthognathic surgical planning using graph CNN with dual embedding module: External validations with multi-hospital datasets.

BACKGROUND AND OBJECTIVE: Despite recent development of AI, prediction of the surgical movement in the maxilla and mandible by OGS might be more difficult than that of tooth movement by orthodontic treatment. To evaluate the prediction accuracy of the surgical movement using pairs of pre-(T0) and post-surgical (T1) lateral cephalograms (lat-ceph) of orthognathic surgery (OGS) patients and dual embedding module-graph convolution neural network (DEM-GCNN) model. METHODS: 599 pairs from 3 institutions were used as training, internal validation, and internal test sets and 201 pairs from other 6 institutions were used as external test set. DEM-GCNN model (IEM, learning the lat-ceph images; LTEM, learning the landmarks) was developed to predict the amount and direction of surgical movement of ANS and PNS in the maxilla and B-point and Md1crown in the mandible. The distance between T1 landmark coordinates actually moved by OGS (ground truth) and predicted by DEM-GCNN model and pre-existed CNN-based Model-C (learning the lat-ceph images) was compared. RESULTS: In both internal and external tests, DEM-GCNN did not exhibit significant difference from ground truth in all landmarks (ANS, PNS, B-point, Md1crown, all P > 0.05). When the accumulated successful detection rate for each landmark was compared, DEM-GCNN showed higher values than Model-C in both the internal and external tests. In violin plots exhibiting the error distribution of the prediction results, both internal and external tests showed that DEM-GCNN had significant performance improvement in PNS, ANS, B-point, Md1crown than Model-C. DEM-GCNN showed significantly lower prediction error values than Model-C (one-jaw surgery, B-point, Md1crown, all P < 0.005; two-jaw surgery, PNS, ANS, all P < 0.05; B point, Md1crown, all P < 0.005). CONCLUSION: We developed a robust OGS planning model with maximized generalizability despite diverse qualities of lat-cephs from 9 institutions.

A spatio-temporal Dirichlet process mixture model for coronavirus disease-19.

Understanding the spatio-temporal patterns of the coronavirus disease 2019 (COVID-19) is essential to construct public health interventions. Spatially referenced data can provide richer opportunities to understand the mechanism of the disease spread compared to the more often encountered aggregated count data. We propose a spatio-temporal Dirichlet process mixture model to analyze confirmed cases of COVID-19 in an urban environment. Our method can detect unobserved cluster centers of the epidemics, and estimate the space-time range of the clusters that are useful to construct a warning system. Furthermore, our model can measure the impact of different types of landmarks in the city, which provides an intuitive explanation of disease spreading sources from different time points. To efficiently capture the temporal dynamics of the disease patterns, we employ a sequential approach that uses the posterior distribution of the parameters for the previous time step as the prior information for the current time step. This approach enables us to incorporate time dependence into our model in a computationally efficient manner without complicating the model structure. We also develop a model assessment by comparing the data with theoretical densities, and outline the goodness-of-fit of our fitted model.

PLM-101 is a novel and potent FLT3/RET inhibitor with less adverse effects in the treatment of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML, FMS-like tyrosine kinase 3 (FLT3) mutations are common and have negative outcomes. However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure. Rearranged during transfection (RET), meanwhile, is a proto-oncogene linked to various types of cancer, but its role in AML has been limited. A previous study showed that activation of RET kinase enhances FLT3 protein stability, leading to the promotion of AML cell proliferation. However, no drugs are currently available that target both FLT3 and RET. This study introduces PLM-101, a new therapeutic option derived from the traditional Chinese medicine indigo naturalis with potent in vitro and in vivo anti-leukemic activities. PLM-101 potently inhibits FLT3 kinase and induces its autophagic degradation via RET inhibition, providing a superior mechanism to that of FLT3 single-targeting agents. Single- and repeated-dose toxicity tests conducted in the present study showed no significant drug-related adverse effects. This study is the first to present a new FLT3/RET dual-targeting inhibitor, PLM-101, that shows potent anti-leukemic activity and fewer adverse effects. PLM-101, therefore, should be considered for use as a potential therapeutic agent for AML.

A Study on the Effects of Muscarinic and Serotonergic Regulation by Bojanggunbi-tang on the Pacemaker Potential of the Interstitial Cells of Cajal in the Murine Small Intestine.

In traditional Korean medicine, the 16-herb concoction Bojanggunbi-tang (BGT) is used to treat various gastrointestinal (GI) diseases. In this study, we investigated the regulatory mechanism underlying the influence of BGT on the interstitial cells of Cajal (ICCs), pacemaker cells in the GI tract. Within 12 h of culturing ICCs in the small intestines of mice, the pacemaker potential of ICCs was recorded through an electrophysiological method. An increase in the BGT concentration induced depolarization and decreased firing frequency. This reaction was suppressed by cholinergic receptor muscarinic 3 (CHRM3) antagonists, as well as 5-hydroxytryptamine receptor (5HTR) 3 and 4 antagonists. Nonselective cation channel inhibitors, such as thapsigargin and flufenamic acid, along with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors, also suppressed the BGT reaction. Guanylate cyclase and protein kinase G (PKG) antagonists inhibited BGT, but adenylate cyclase and protein kinase A antagonists had no effect. In conclusion, we demonstrated that BGT acts through CHRM3, 5HTR3, and 5HTR4 to regulate intracellular Ca2+ concentrations and the PKC, MAPK, guanylate cycle, and PKG signaling pathways.

Analysis of Network Pharmacological Efficacy and Therapeutic Effectiveness in Animal Models for Functional Dyspepsia of Foeniculi fructus.

For centuries, Foeniculi fructus (F. fructus) has been used as a traditional herbal medicine in China and Europe and is widely used as a natural therapy for digestive disorders, including indigestion, flatulence, and bloating. The mechanism of F. fructus that alleviates functional dyspepsia was analyzed through network pharmacology, and its therapeutic effect on an animal model of functional dyspepsia were investigated. The traditional Chinese medicine systems pharmacology (TCMSP) database was used to investigate the compounds, targets, and associated diseases of F. fructus. Information on the target genes was classified using the UniProtdatabase. Using the Cytoscape 3.9.1 software, a network was constructed, and the Cytoscape string application was employed to examine genes associated with functional dyspepsia. The efficacy of F. fructus on functional dyspepsia was confirmed by treatment with its extract in a mouse model of loperamide-induced functional dyspepsia. Seven compounds targeted twelve functional dyspepsia-associated genes. When compared to the control group, F. fructus exhibited significant suppression of symptoms in a mouse model of functional dyspepsia. The results of our animal studies indicated a close association between the mechanism of action of F. fructus and gastrointestinal motility. Based on animal experimental results, the results showed that F. fructus provided a potential means to treat functional dyspepsia, suggesting that its medical mechanism for functional dyspepsia could be described by the relationship between seven key compounds of F. fructus, including oleic acid, ß-sitosterol, and 12 functional dyspepsia-related genes.

Herbal medicine, Banxia-xiexin tang, for functional dyspepsia: a systematic review and meta-analysis.

Background: The demand for complementary and alternative medicine for the management of functional dyspepsia (FD) is increasing due to the insufficient efficacy of conventional treatment options. In Asia, the Chinese herbal medicine formula Banxia-xiexin tang (BXT) has been used to treat FD. Methods: We searched 11 digital medical databases on 1 September 2021. Randomized controlled trials (RCTs) that investigated the efficacy of BXT or combination therapy (BXT plus Western medicines) for FD were selected. The outcome parameters were total clinical efficacy rate (TCE), motilin level, symptom checklist-90-revised (SCL-90-R), and visual analog scale (VAS) for dyspepsia and adverse events. Cochrane risk of bias tool 2.0 (RoB 2) was used for the quality assessment of included studies. Results: The meta-analysis comprised 57 RCTs with 5,525 participants. BXT was more efficacious, with a higher TCE than Western medicine. Combination therapy (BXT plus Western medicine) also resulted in a higher TCE than Western medicine. Combination therapy improved motilin levels and psychological symptoms to a greater extent than Western medicine, evidenced by a higher SCL-90-R score. However, no significant difference in VAS scores was observed between the BXT and placebo groups. BXT and combination therapy were associated with fewer adverse events than Western medicine or placebo. Conclusion: Our findings suggest that BXT and its combination therapy may be an effective and safe alternative treatment for FD. More RCTs with better methodologies are required to strengthen this evidence. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019123285], identifier [CRD42019123285].

Performance of Early Warning Scoring Systems Regarding Adverse Events of Unanticipated Clinical Deterioration in Complementary and Alternative Medicine Hospitals.

PURPOSE: This study aims to examine the performance of early warning scoring systems regarding adverse events of unanticipated clinical deterioration in complementary and alternative medicine hospitals. METHODS: A medical record review of 500 patients from 5-year patient data in two traditional Korean medicine hospitals was conducted. Unanticipated clinical deterioration events included unexpected in-hospital mortality, cardiac arrest, and unplanned transfers to acute-care conventional medicine hospitals. Scores of the Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), and National Early Warning Score 2 (NEWS2) were calculated. Their performance was evaluated by calculating areas under the receiver-operating characteristic curve for the event occurrence. Multiple logistic regression analyses were performed to determine the factors associated with event occurrence. RESULTS: The incidence of unanticipated clinical deterioration events was 1.1% (225/21101). The area under the curve of MEWS, NEWS, and NEWS2 was .68, .72, and .72 at 24 hours before the events, respectively. NEWS and NEWS2, with almost the same performance, were superior to MEWS (p = .009). After adjusting for other variables, patients at low-medium risk (OR = 3.28; 95% CI = 1.02-10.55) and those at medium and high risk (OR = 25.03; 95% CI = 2.78-225.46) on NEWS2 scores were more likely to experience unanticipated clinical deterioration than those at low risk. Other factors associated with the event occurrence included frailty risk scores, clinical worry scores, primary medical diagnosis, prescribed medicine administration, acupuncture treatment, and clinical department. CONCLUSIONS: The three early warning scores demonstrated moderate-to-fair performance for clinical deterioration events. NEWS2 can be used for early identification of patients at high risk of deterioration in complementary and alternative medicine hospitals. Additionally, patient, care, and system factors need to be considered to improve patient safety.

Ancillary investigations for death determination in infants and children: a systematic review and meta-analysis.

PURPOSE: We performed a systematic review and meta-analysis to determine the diagnostic test accuracy of ancillary investigations for declaration of death by neurologic criteria (DNC) in infants and children. SOURCE: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases from their inception to June 2021 for relevant randomized controlled trials, observational studies, and abstracts published in the last three years. We identified relevant studies using Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology and a two-stage review. We assessed the risk of bias using the QUADAS-2 tool, and applied Grading of Recommendations Assessment, Development, and Evaluation methodology to determine the certainty of evidence. A fixed-effects model was used to meta-analyze pooled sensitivity and specificity data for each ancillary investigation with at least two studies. PRINCIPAL FINDINGS: Thirty-nine eligible manuscripts assessing 18 unique ancillary investigations (n = 866) were identified. The sensitivity and specificity ranged from 0.00 to 1.00 and 0.50 to 1.00, respectively. The quality of evidence was low to very low for all ancillary investigations, with the exception of radionuclide dynamic flow studies for which it was graded as moderate. Radionuclide scintigraphy using the lipophilic radiopharmaceutical 99mTc-hexamethylpropyleneamine oxime (HMPAO) with or without tomographic imaging were the most accurate ancillary investigations with a combined sensitivity of 0.99 (95% highest density interval [HDI], 0.89 to 1.00) and specificity of 0.97 (95% HDI, 0.65 to 1.00). CONCLUSION: The ancillary investigation for DNC in infants and children with the greatest accuracy appears to be radionuclide scintigraphy using HMPAO with or without tomographic imaging; however, the certainty of the evidence is low. Nonimaging modalities performed at the bedside require further investigation. STUDY REGISTRATION: PROSPERO (CRD42021278788); registered 16 October 2021.

RéSUMé: OBJECTIF: Nous avons réalisé une revue systématique et une méta-analyse pour déterminer la précision des tests diagnostiques des examens auxiliaires pour la déclaration du décès selon des critères neurologiques (DCN) chez les nourrissons et les enfants. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, EMBASE, Web of Science et Cochrane de leur création jusqu'en juin 2021 pour trouver des études randomisées contrôlées, des études observationnelles et des résumés pertinents publiés au cours des trois dernières années. Nous avons identifié les études pertinentes utilisant la méthodologie PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) et une revue en deux étapes. Nous avons évalué le risque de biais en utilisant l'outil QUADAS-2 et appliqué la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation) afin d'évaluer la certitude des données probantes. Un modèle à effets fixes a été utilisé pour méta-analyser les données de sensibilité et de spécificité regroupées pour chaque examen auxiliaire avec au moins deux études. CONSTATATIONS PRINCIPALES: Trente-neuf manuscrits admissibles évaluant 18 examens auxiliaires uniques (n = 866) ont été identifiés. La sensibilité et la spécificité variaient de 0,00 à 1,00 et de 0,50 à 1,00, respectivement. La qualité des données probantes était faible à très faible pour tous les examens auxiliaires, à l'exception des études de circulation nucléaire dynamique, pour lesquelles elle a été classée comme modérée. La scintigraphie nucléaire à l'aide du produit radiopharmaceutique lipophile 99mTc- hexa-méthyl-propylène amine oxime (HMPAO) avec ou sans imagerie tomographique était à la base des examens auxiliaires les plus précis, avec une sensibilité combinée de 0,99 (intervalle de densité le plus élevé [IDE] à 95 %, 0,89 à 1,00) et une spécificité de 0,97 (IDE à 95 %, 0,65 à 1,00). CONCLUSION: L'examen auxiliaire pour un DCN chez les nourrissons et les enfants offrant la plus grande précision semble être la scintigraphie nucléaire utilisant le HMPAO avec ou sans imagerie tomographique; cependant, la certitude des données probantes est faible. Les modalités sans imagerie réalisées au chevet du patient nécessitent un examen plus approfondi. Enregistrement de l'étude: PROSPERO (CRD42021278788); enregistrée le 16 octobre 2021.

Efficacy and safety of the herbal formula Naesohwajung-tang for functional dyspepsia: a randomized, double-blind, placebo-controlled, multi-center trial.

Background: Current treatment and management options for functional dyspepsia (FD) often fail to alleviate symptoms. Naesohwajung-tang (NHT) is a herbal formula frequently used to treat functional dyspepsia in traditional Korean medicine. However, few animal and case reports on the use of Naesohwajung-tang for functional dyspepsia treatment exist, and the clinical evidence remains deficient. Objectives: This study aimed to evaluate the efficacy of Naesohwajung-tang in patients with functional dyspepsia. Methods: We enrolled 116 patients with functional dyspepsia at two study sites in this 4 weeks, randomized, double-blind, placebo-controlled trial and randomly assigned them to either the Naesohwajung-tang or placebo group. To evaluate the efficacy of Naesohwajung-tang, the primary endpoint was a score on the total dyspepsia symptom (TDS) scale after treatment. The overall treatment effect (OTE), single dyspepsia symptom (SDS) scale, food retention questionnaire (FRQ), Damum questionnaire (DQ), functional dyspepsia-related quality of life (FD-QoL) questionnaire, and gastric myoelectrical activity measured using electrogastrography were evaluated as secondary outcomes. Laboratory tests were performed to confirm the safety of the intervention. Results: The 4 weeks administration of Naesohwajung-tang granules demonstrated a significantly higher reduction in the total dyspepsia symptom (p < 0.05) and a higher degree of improvement in the total dyspepsia symptom (p < 0.01) than the placebo group. Patients who underwent Naesohwajung-tang had a significantly higher overall treatment effect and a greater increase in the degree of improvement in scores such as epigastric burning, postprandial fullness, early satiation, functional dyspepsia-related quality of life, and Damum questionnaire (p < 0.05). Additionally, the Naesohwajung-tang group showed a greater effect in preventing a decrease in the percentage of normal gastric slow waves after meals than the placebo group. As a result of subgroup analyses using the degree of improvement in total dyspepsia symptom, Naesohwajung-tang was found to be more effective than placebo in female, younger patients (<65 years), with a high body-mass index (≥22), overlap type, food retention type, and Dampness and heat in the spleen and stomach systems pattern. There was no significant difference in the incidence of adverse events between the two groups. Conclusion: This is the first randomized clinical trial to verify that Naesohwajung-tang leads on symptom relief in patients with functional dyspepsia. Clinical Trial Registration: https://cris.nih.go.kr/cris/search/detailSearch.do/17613, identifier KCT0003405.

Safety and efficacy of Xiaoyao-san for the treatment of functional dyspepsia: a systematic review and meta-analysis of randomized controlled trials.

Objective: Although Xiaoyao-san (XYS) is a popular herbal remedy for indigestion, there is insufficient evidence to recommend it as a treatment option for functional dyspepsia (FD). This review aimed to assess the safety and efficacy of XYS in patients with FD, compared to conventional Western medicine (WM). Methods: Two independent reviewers searched for randomized controlled trials (RCTs) using 11 electronic databases, including Medline and Embase, to evaluate therapeutic effects of XYS on FD up to 31 January 2023. The primary outcome was the total clinical efficacy rate (TCE), and secondary outcomes included scores of dyspepsia-related symptoms (DSS) and incidence of adverse events (AEs). The risk of bias was evaluated using the Cochrane collaboration tool, and data synthesis and subgroup analyses were performed using the Review Manager program. Results: Six studies involving 707 participants were included in the meta-analysis. XYS significantly improved TCE compared to WM (RR = 1.15, 95% CI: 1.05, 1.26, p = 0.002) with high heterogeneity (I 2 = 59%, p = 0.06). Combination therapy also showed higher TCE than WM alone (RR = 1.22, 95% CI: 1.05, 1.41, p = 0.008), and the heterogeneity was low (I 2 = 0%, p = 0.86). The results showed a greater reduction in DSS in the XYS and combination therapy groups than in the WM alone group (SMD = -0.72, 95% CI: -0.90, -0.53, p < 0.00001) with low heterogeneity (I 2 = 44%, p = 0.15), especially for abdominal distension and upper abdominal pain. AEs occurred less frequently in the XYS and combination therapy groups than in the WM alone group (RR = 0.20, 95% CI: 0.07, 0.63, p = 0.006), and the heterogeneity was low (I 2 = 45%, p = 0.18). The certainty of the evidence for each outcome was rated from "very low" to "high." Conclusion: This review suggests that XYS is effective and safe for reducing complaints in patients with FD. However, high-quality RCTs should be conducted to establish more convincing therapeutic evidence of XYS for the treatment of FD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, CRD42020178842.