Ultrastable 3D Heterogeneous Integration via N-Heterocyclic Carbene Self-Assembled Nanolayers.

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

Effect of Trimebutine and Rifaximin on Breath Hydrogen and Methane by Glucose Breath Test in Patients With Functional Bloating: A Randomized Double-blind Clinical Trial.

Background/Aims: Drugs that stabilize intestinal motility may improve the efficacy of nonabsorbable antibiotics, such as rifaximin, against small intestinal bacterial overgrowth (SIBO). We compared the efficacy of rifaximin alone with that of its combination with trimebutine maleate against SIBO. Methods: We performed a randomized double-blind placebo-controlled trial (https://cris.nih.go.kr, no. KCT0004836) that included patients with functional bloating, no constipation, and SIBO using the hydrogen (H2)-methane (CH4) glucose breath test (GBT). Patients were randomized into 2 groups in a 1:1 ratio, namely rifaximin (1200 mg/day) + trimebutine maleate (600 mg/day) group and rifaximin + placebo group, for 2 weeks. Patients completed a symptom questionnaire and underwent a GBT at baseline and at 1 month after treatment withdrawal. The primary outcome was SIBO eradication. The secondary outcomes included changes in the concentrations of exhaled gases, symptoms, and presence of adverse events. Results: The complete eradication rate of SIBO was 35.9% (14/39) in the rifaximin group, and 34.1% (14/41) in the combined group with no significant differences. In both groups, no significant differences were observed in GBT profiles before and after the treatment, respectively. However total breath H2 and CH4 concentration were conspicuously decreased in the combined group after treatment. The combined group exhibited substantial relief of bloating. The adverse events were similar in the 2 groups. Conclusion: While the combination therapy was not superior over rifaximin alone for SIBO eradication, it improves the symptom of bloating with numerically reducing the concentration of breath H2/CH4.

Vitamin D Deficiency as a Risk Factor of Tinnitus: An Epidemiological Study.

OBJECTIVES: Vitamin D deficiency as a risk factor of tinnitus has not been well known. We tried to evaluate the association between the serum 25-(OH) vitamin D levels and tinnitus among the Korean population to propose the possible role of serum vitamin D in patients with tinnitus. METHODS: This cross-sectional study investigated the potential risk factors of tinnitus in relation to serum 25(OH)D levels within the Korean population. It encompassed a health interview, nutrition assessment, and a health examination. Data was sourced from the KNHANES V (2010-2012), conducted by the Division of Health and Nutritional Survey under the Korean Centers for Disease Control and Prevention (KCDCP). Participants were chosen from various sampling units categorized by geography, gender, and age group. The selection was facilitated through household registries using a stratified, multistage, clustered probability sampling approach. RESULTS: Data of 16 408 subjects were collected in this study. There were significant differences in gender, economic status, educational level, and sun exposure duration between the tinnitus and non-tinnitus groups. Serum 25(OH) vitamin D level between hearing loss and normal hearing was also significantly different. The logistic regression models with serum 25(OH) vitamin D quartile and tinnitus as the dependent variable, which were controlled for age, sex, smoking status, BMI, diabetes, hypertension, sun exposure, regular exercise, income, and education, eventually demonstrated that serum vitamin D deficiency and low sun exposure duration significantly increased the risk of tinnitus development. CONCLUSION: This study demonstrated a significant association between serum vitamin D levels and tinnitus, driven by large epidemiological data. The results of our study provide baseline data for further research to investigate the role of vitamin D in the pathogenesis and management of tinnitus.

Exploring the dietary and therapeutic potential of licorice (Glycyrrhiza uralensis Fisch.) sprouts.

ETHNOPHARMACOLOGICAL RELEVANCE: This research substantiates the traditional use of Glycyrrhiza uralensis Fisch. for liver health, with scientific evidence of the non-toxic and lipid-lowering properties of licorice sprout extracts. The sprouts' rich mineral and amino acid content, along with their strong antioxidant activity, reinforce their value in traditional medicine. These findings bridge ancient herbal practices with modern science, highlighting licorice's potential in contemporary therapeutic applications. AIM OF THE STUDY: The study aimed to investigate the dietary and medicinal potential of G. uralensis sprouts by assessing their safety, nutritional content, and antioxidant properties using both plant and animal models. Specifically, the study sought to determine the effects of different sizes of licorice sprouts on lipid metabolism in human liver cancer cells and their overall impact on rat health indicators. MATERIALS AND METHODS: The study examined the effects of aqueous and organic extracts from G. uralensis sprouts of varying lengths on the cytotoxicity, lipid metabolism, and antioxidant activity in HepG2 cells, alongside in vivo impacts on Sprague-Dawley rats, using MTT, ICP, and HPLC. It aimed to assess the potential health benefits of licorice sprouts by analyzing their protective effects against oxidative stress and their nutritional content. RESULTS: Licorice sprout extracts from G. uralensis demonstrated no cytotoxicity in HepG2 cells, significantly reduced lipid levels, and enhanced antioxidant activities, with the longest sprouts (7 cm) showing higher mineral, sugar, and arginine content as well as increased glycyrrhizin and liquiritigenin. In vivo studies with Sprague-Dawley rats revealed weight gain and improved antioxidant enzyme activities in blood plasma and liver tissues after consuming the extracts, highlighting the sprouts' dietary and therapeutic potential. CONCLUSIONS: This study is the first to demonstrate that G. uralensis sprouts, particularly those 7 cm in length, have no cytotoxic effects, reduce lipids, and have high mineral and antioxidant contents, offering promising dietary and therapeutic benefits.

Hearing Rehabilitation With a Chat-Based Mobile Auditory Training Program in Experienced Hearing Aid Users: Prospective Randomized Controlled Study.

Background: Hearing rehabilitation with auditory training (AT) is necessary to improve speech perception ability in patients with hearing loss. However, face-to-face AT has not been widely implemented due to its high cost and personnel requirements. Therefore, there is a need for the development of a patient-friendly, mobile-based AT program. Objective: In this study, we evaluated the effectiveness of hearing rehabilitation with our chat-based mobile AT (CMAT) program for speech perception performance among experienced hearing aid (HA) users. Methods: A total of 42 adult patients with hearing loss who had worn bilateral HAs for more than 3 months were enrolled and randomly allocated to the AT or control group. In the AT group, CMAT was performed for 30 minutes a day for 2 months, while no intervention was provided in the control group. During the study, 2 patients from the AT group and 1 patient from the control group dropped out. At 0-, 1- and 2-month visits, results of hearing tests and speech perception tests, compliance, and questionnaires were prospectively collected and compared in the 2 groups. Results: The AT group (n=19) showed better improvement in word and sentence perception tests compared to the control group (n=20; P=.04 and P=.03, respectively), while no significant difference was observed in phoneme and consonant perception tests (both P>.05). All participants were able to use CMAT without any difficulties, and 85% (17/20) of the AT group completed required training sessions. There were no changes in time or completion rate between the first and the second month of AT. No significant difference was observed between the 2 groups in questionnaire surveys. Conclusions: After using the CMAT program, word and sentence perception performance was significantly improved in experienced HA users. In addition, CMAT showed high compliance and adherence over the 2-month study period. Further investigations are needed to validate long-term efficacy in a larger population. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) KCT0006509; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22110&search_page=L.

Dual-light emitting 3D encryption with printable fluorescent-phosphorescent metal-organic frameworks.

Optical encryption technologies based on room-temperature light-emitting materials are of considerable interest. Herein, we present three-dimensional (3D) printable dual-light-emitting materials for high-performance optical pattern encryption. These are based on fluorescent perovskite nanocrystals (NCs) embedded in metal-organic frameworks (MOFs) designed for phosphorescent host-guest interactions. Notably, perovskite-containing MOFs emit a highly efficient blue phosphorescence, and perovskite NCs embedded in the MOFs emit characteristic green or red fluorescence under ultraviolet (UV) irradiation. Such dual-light-emitting MOFs with independent fluorescence and phosphorescence emissions are employed in pochoir pattern encryption, wherein actual information with transient phosphorescence is efficiently concealed behind fake information with fluorescence under UV exposure. Moreover, a 3D cubic skeleton is developed with the dual-light-emitting MOF powder dispersed in 3D-printable polymer filaments for 3D dual-pattern encryption. This article outlines a universal principle for developing MOF-based room-temperature multi-light-emitting materials and a strategy for multidimensional information encryption with enhanced capacity and security.

Significance of traditional herbal medicine for dyslipidemia.

Dyslipidemia is a multifactorial disorder that is a causative factor and risk factor for cardiovascular disease. The incidence of dyslipidemia is expected to increase because of the presence of comorbidities. Although several lipid-lowering drugs have been developed and approved, they are not completely effective and are associated with side effects. Traditional herbal medicine (THM) represents an alternative and complementary approach for managing dyslipidemia because of its low toxicity and beneficial effects, such as anti-inflammatory and antioxidant effects. This review focuses on our current understanding of the antidyslipidemic effect of THMs and discusses the associated regulatory mechanisms. The current findings indicate that THM may lead to the development of novel therapeutic regimens for dyslipidemia.

Cheong-sang-bang-pung-san alleviated hepatic lipid accumulation by regulating lipid metabolism in vitro and in vivo.

Introduction: The occurrence of fatty liver disease, resulting from the accumulation of excessive fat within the liver, has been showing a significant and rapid increase. This study aimed to evaluate the therapeutic effects of Cheong-sang-bang-pung-san extract (CB) on fatty liver disease, and to elucidate the underlying mechanisms. Methods: We used a high-fat diet (HFD)-fed fatty liver mice and free fatty acid (FFA) induced HepG2 cell lipid accumulation model. The levels of serum, hepatic, and intracellular lipid content were assessed. Histopathological staining was used to evaluate the extent of hepatic lipid accumulation. Real-time polymerase chain reaction and Western blotting were conducted to examine the expression of factors associated with lipid metabolism. Results: We demonstrated that treatment with CB dramatically reduced body weight, liver weight, and fat mass, and improved the serum and hepatic lipid profiles in HFD-induced fatty liver mice. Additionally, CB alleviated lipid accumulation in HFD-fed mice by controlling lipid metabolism, including fatty acid uptake, triglyceride and cholesterol synthesis, and fatty acid oxidation, at the mRNA as well as protein levels. In free fatty acid-treated HepG2 cells, CB significantly reduced intracellular lipid accumulation by regulating lipid metabolism via the activation of AMP-activated protein kinase. Conclusion: These findings provide insights into the mechanisms underlying CB's effects on liver steatosis and position of CB as a potential therapeutic candidate for managing lipid metabolic disorders.

Protective Effects of Melatonin in High-Fat Diet-Induced Hepatic Steatosis via Decreased Intestinal Lipid Absorption and Hepatic Cholesterol Synthesis.

BACKGRUOUND: The preventative effect of melatonin on the development of obesity and the progression of fatty liver under a high-fat diet (HFD) has been well elucidated through previous studies. We investigated the mechanism behind this effect regarding cholesterol biosynthesis and regulation of cholesterol levels. METHODS: Mice were divided into three groups: normal chow diet (NCD); HFD; and HFD and melatonin administration group (HFD+M). We assessed the serum lipid profile, mRNA expression levels of proteins involved in cholesterol synthesis and reabsorption in the liver and nutrient transporters in the intestines, and cytokine levels. Additionally, an in vitro experiment using HepG2 cells was performed. RESULTS: Expression of hepatic sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and low-density lipoprotein receptor (LDLR) demonstrated that melatonin administration significantly reduces hepatic cholesterol synthesis in mice fed an HFD. Expression of intestinal sodium-glucose transporter 1 (SGLT1), glucose transporter 2 (GLUT2), GLUT5, and Niemann-pick C1-like 1 (NPC1L1) demonstrated that melatonin administration significantly reduces intestinal carbohydrate and lipid absorption in mice fed an HFD. There were no differences in local and circulatory inflammatory cytokine levels among the NCD, HFD, and HFD+M group. HepG2 cells stimulated with palmitate showed reduced levels of SREBP, LDLR, and HMGCR indicating these results are due to the direct mechanistic effect of melatonin on hepatocytes. CONCLUSION: Collectively, these data indicate the mechanism behind the protective effects of melatonin from weight gain and liver steatosis under HFD is through a reduction in intestinal caloric absorption and hepatic cholesterol synthesis highlighting its potential in the treatment of obesity and fatty liver disease.

Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2'-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia-Reperfusion Injury.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, exerts anti-inflammatory effects and plays a protective role in arterial thrombosis; however, its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2'-FL and its potential mechanisms in a mouse model of ischemic stroke. Neurological score and behavior tests revealed that 2'-FL promoted the recovery of neurological deficits and motor function in middle cerebral artery occlusion (MCAO) mice, and that 2'FL led to a reduction in the size of cerebral infarct. Biochemical studies showed that administration of 2'-FL led to a reduction of reactive oxygen species (ROS)-related products in the brain of MCAO mice. 2'-FL upregulated IL-10 and downregulated TNF-α level. In addition, 2'-FL enhanced M2-type microglial polarization and upregulated CD206 expression at 7 days after MCAO. At 3 days after MCAO, 2'-FL increased IL-4 levels and activated STAT6. Our data show that 2'-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type microglial polarization in MCAO mice. These results demonstrate that 2'-FL is a potentially effective therapeutic agent for ischemic stroke.

An optimized herbal medicine containing Scutellaria baicalensis Georgi, Alisma orientale Juzepzuk, and Atractylodes japonica Koidzumi has potent antiplatelet and antithrombotic activities.

Background and aim: Platelet-derived thrombosis is important in the pathogenesis of cardiovascular diseases. HTB is an optimized herbal medicine including Scutellaria baicalensis Georgi, Alisma orientale Juzepzuk, and Atractylodes japonica Koidzumi. It is widely used in traditional medicine due to its anti-inflammatory and antioxidant effects. However, its antiplatelet and antithrombotic activities have not been completely validated. The current study aimed to examine the inhibitory effect of the novel herb formula HTB against platelet activation and thrombus formation. Experimental procedure: The antiplatelet activities of HTB via platelet aggregation, granule secretion, reactive oxygen species generation, and intracellular calcium mobilization were evaluated. Moreover, the antithrombotic effect of HTB via FeCl3-induced arterial thrombus formation in vivo in mice was assessed. The inhibitory effect of HTB against primary hemostasis was investigated based on transection tail bleeding time. Results and conclusion: HTB treatment significantly inhibited glycoprotein VI-mediated platelet aggregation, granule secretion, reactive oxygen species generation, and intracellular calcium mobilization. Biochemical studies revealed that HTB inhibited glycoprotein VI-mediated platelet signal transduction during cell activation. Further, its antioxidant effect might be derived by reducing the phosphorylation of the p47phox/Hic5 axis signalosome. Oral HTB treatment was effective in decreasing FeCl3-induced arterial thrombus formation without prolonging the tail bleeding time. HTB can be an effective therapeutic agent against thrombotic diseases.

2'-Fucosyllactose and 3-Fucosyllactose Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Modulating the Intestinal Microbiome.

Ulcerative colitis is an inflammatory bowel disease (IBD) with relapsing and remitting patterns, and it is caused by varied factors, such as the intestinal inflammation extent and duration. We examined the preventative effects of human milk oligosaccharides (HMOs) on epithelial barrier integrity and intestinal inflammation in an interleukin (IL)-6-induced cell model and dextran sodium sulfate (DSS)-induced acute mouse colitis model. HMOs including 2'-fucosyllactose (FL) and 3-FL and positive controls including fructooligosaccharide (FOS) and 5-acetylsalicylic acid (5-ASA) were orally administrated once per day to C57BL/6J mice with colitis induced by 5% DSS in the administered drinking water. 2'-FL and 3-FL did not affect the cell viability in Caco-2 cells. Meanwhile, these agents reversed IL-6-reduced intestinal barrier function in Caco-2 cells. Furthermore, 2'-FL and 3-FL reversed the body weight loss and the remarkably short colon lengths in DSS-induced acute colitis mice. Moreover, 2'-FL and 3-FL obviously protected the decreasing expression of zonula occluden-1 and occludin in colon tissue relative to the findings in the DSS-treated control group. 2'-FL and 3-FL significantly reduced IL-6 and tumor necrosis factor-α levels in serum relative to the control findings. The summary of these results shows that HMOs prevent colitis mainly by enhancing intestinal barrier function and advancing anti-inflammatory responses. Therefore, HMOs might suppress inflammatory responses and represent candidate treatments for IBD that protect intestinal integrity.

Silencing Pulsatile Tinnitus: A Novel Technique of Periosteal Flap Obliteration for Sigmoid Sinus Diverticulum Variants.

OBJECTIVE: Review of a sigmoid sinus diverticuli (SSDi) variants surgically managed with a novel technique using an inferior periosteal flap. STUDY DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Patients presenting with pulsatile tinnitus to a tertiary referral center between January 1, 2015, and June 31, 2021, who were diagnosed with SSDi variants on CT temporal bone and who received surgical management for these SSDi variants. INTERVENTIONS: Obliteration of SSDi variants using a novel technique with an inferiorly based periosteal flap. MAIN OUTCOME MEASURES: Pure-tone audiometry, Tinnitus Handicap Inventory score, and visual analogue scale score for tinnitus severity (loudness, awareness, annoyance, and effect on life). RESULTS: Include statistical measures as appropriate. CONCLUSIONS: We would like to propose the use of an inferiorly based periosteal flap as an option for obliteration and concomitant hemostasis of more sizeable or complex (e.g., bifid) SSDi. Further study of this technique with a long-term follow-up will be needed to evaluate its long-term safety and efficacy.

Humidity-Tolerant Moisture-Driven Energy Generator with MXene Aerogel-Organohydrogel Bilayer.

Free-standing and film-type moisture-driven energy generators (MEGs) that harness the preferential interaction of ionized moisture with hydrophilic materials are interesting because of their wearability and portability without needing a water container. However, most such MEGs work in limited humidity conditions, which provide a substantial moisture gradient. Herein, we present a high-performance MEG with sustainable power-production capability in a wide range of environments. The bilayer-based device comprises a negatively surface-charged, hydrophilic MXene (Ti3C2Tx) aerogel and polyacrylamide (PAM) ionic hydrogel. The preferential selection on the MXene aerogel of positive charges supplied from the salts and water in the hydrogel is predicted by the first-principle simulation, which results in a high electric output in a wide relative humidity range from 20% to 95%. Furthermore, by replacing the hydrogel with an organohydrogel of PAM that has excellent water retention and structural stability, a device with long-term electricity generation is realized for more than 15 days in a broad temperature range (from -20 to 80 °C). Our MXene aerogel MEGs connected in series supply sufficient power for commercial electronic components in various outdoor environments. Moreover, an MXene aerogel MEG works as a self-powered sensor for recognizing finger bending and facial expression.

Lactase Deficiency Diagnosed by Endoscopic Biopsy-based Method is Associated With Positivity to Glucose Breath Test.

Background/Aims: Lactase deficiency, which has many similarities with small intestinal bacterial overgrowth (SIBO), causes various gastrointestinal symptoms. We estimate the prevalence of SIBO in patients with intestinal symptoms from dairy products and investigate the association between lactase deficiency (LD) and SIBO. Methods: This prospective study included patients with functional intestinal symptoms from dairy product indigestion. A questionnaire on gastrointestinal symptoms, a hydrogen (H2)-methane glucose breath test (GBT) for SIBO, and lactose intolerance quick test (LQT) for LD using upper gastrointestinal endoscopy were performed. Results: A total of 88 patients, 29 (33.0%) with severe and 36 (40.9%) with mild LD were included. Sixteen patients (18.2%) were GBT positive. Patients with LQT negativity indicating severe LD showed a higher positivity to GBT or GBT (H2) than the historic controls (27.6% vs 6.7%, P = 0.032). There was no difference in the items on the symptom questionnaire according to the presence of LD or SIBO, except for higher symptom scores for urgency in GBT-positive patients. There were more LQT-negative patients in the GBT (H2)-positive group than in the other groups (27.6% vs 10.2%, P = 0.036). Moreover, only GBT (H2)-positivity was significantly associated with a higher risk of LQT negativity in multivariate analysis (OR, 4.19; P = 0.029). Conclusions: SIBO producing H2 is common in patients with severe LD suspected lactose intolerance. SIBO may be a new therapeutic target for managing intestinal symptoms in patients with lactose intolerance.

TYRO3 blockade enhances anti-PD-1 therapy response by modulating expression of CCN1 in tumor microenvironment.

BACKGROUND: Immunological contexture differs across malignancies, and understanding it in the tumor microenvironment (TME) is essential for development of new anticancer agents in order to achieve synergistic effects with anti-programmed cell death protein-1 (PD-1) therapy. TYRO3, AXL, and MERTK receptors are bi-expressed in both cancer and immune cells, and thus emerge as promising targets for therapeutic intervention. Whereas AXL and MERTK have been extensively studied, the role of TYRO3, in the TME, is still undetermined. METHODS: Here, we screened the TYRO3-focused chemical library consisting of 208 compounds and presented a potent and highly selective TYRO3 inhibitor, KRCT87. We explored the role of TYRO3 using mouse engrafting MC38 or 4T1 tumors. We validated the results using flow cytometry, RNA sequencing analysis, gene knockdown or overexpression, ex vivo immune cells isolation from mouse models, immunoblotting and quantitative PCR. Flow cytometry was used for the quantification of cell populations and immunophenotyping of macrophages and T cells. Co-cultures of macrophages and T cells were performed to verify the role of CCN1 in the tumors. RESULTS: TYRO3 blockade boosts antitumor immune responses in both the tumor-draining lymph nodes and tumors in MC38-syngeneic mice models. Moreover, the combination of KRCT87 and anti-PD-1 therapy exerts significant synergistic antitumor effects in anti-PD-1-non-responsive 4T1-syngeneic model. Mechanistically, we demonstrated that inhibition of TYRO3-driven CCN1 secretion fosters macrophages into M1-skewing phenotypes, thereby triggering antitumor T-cell responses. CCN1 overexpression in MC38 tumors diminishes responsiveness to anti-PD-1 therapy. CONCLUSIONS: The activated TYRO3-CCN1 axis in cancer could dampen anti-PD-1 therapy responses. These findings highlight the potential of TYRO3 blockade to improve the clinical outcomes of anti-PD-1 therapy.

Efficacies of prokinetics and rifaximin on the positivity of a glucose breath test in patients with functional dyspepsia: a randomized trial.

BACKGROUND AND AIM: prokinetics could eradicate small intestinal bacterial overgrowth. This study aimed to evaluate the efficacy of mosapride, rifaximin and a combination of mosapride and rifaximin for the treatment of small intestinal bacterial overgrowth. METHODS: we randomly assigned patients with functional dyspepsia diagnosed with small intestinal bacterial overgrowth in a 1:1:1 ratio to receive mosapride, rifaximin or a combination of both for two weeks. The hydrogen-methane glucose breath test and symptom questionnaire were surveyed before and after the treatment. Primary outcome was eradication rate of small intestinal bacterial overgrowth. Secondary outcomes were changes in the gas concentration, symptoms and safety. RESULTS: the eradication rates were 17.2 % (5/29) for mosapride, 32.1 % (9/28) for rifaximin, and 34.6 % (9/26) for the combined groups, with no significant differences among the three groups. Total hydrogen concentration during the glucose breath test significantly decreased in the rifaximin group (p = 0.001). Total methane concentration significantly decreased in the rifaximin and combined groups (p = 0.005). Significant symptomatic improvements were observed in chest and abdominal discomfort with mosapride, in flatulence with rifaximin, and in chest discomfort with the combined groups. Adverse events were similar between the groups. CONCLUSIONS: rifaximin has an advantage of reducing gas, whereas mosapride can help to decrease breath hydrogen concentration. Certain intestinal symptoms improved with mosapride alone or combined with rifaximin.

Efficacies of prokinetics and rifaximin on the positivity of a glucose breath test in patients with functional dyspepsia: a randomized trial

Background and aim: prokinetics could eradicate small intestinal bacterial overgrowth. This study aimed to evaluate the efficacy of mosapride, rifaximin and a combination of mosapride and rifaximin for the treatment of small intestinal bacterial overgrowth. Methods: we randomly assigned patients with functional dyspepsia diagnosed with small intestinal bacterial overgrowth in a 1:1:1 ratio to receive mosapride, rifaximin or a combination of both for two weeks. The hydrogen-methane glucose breath test and symptom questionnaire were surveyed before and after the treatment. Primary outcome was eradication rate of small intestinal bacterial overgrowth. Secondary outcomes were changes in the gas concentration, symptoms and safety. Results: the eradication rates were 17.2 % (5/29) for mosapride, 32.1 % (9/28) for rifaximin, and 34.6 % (9/26) for the combined groups, with no significant differences among the three groups. Total hydrogen concentration during the glucose breath test significantly decreased in the rifaximin group (p = 0.001). Total methane concentration significantly decreased in the rifaximin and combined groups (p = 0.005). Significant symptomatic improvements were observed in chest and abdominal discomfort with mosapride, in flatulence with rifaximin, and in chest discomfort with the combined groups. Adverse events were similar between the groups. Conclusions: rifaximin has an advantage of reducing gas, whereas mosapride can help to decrease breath hydrogen concentration. Certain intestinal symptoms improved with mosapride alone or combined with rifaximin (AU)

Sinomenium acutum Modulates Platelet Aggregation and Thrombus Formation by Regulating the Glycoprotein VI-Mediated Signalosome in Mice.

Sinomenium acutum (SA) has long been used as a traditional medicine in China, Japan, and Korea to treat a wide range of diseases. It has been traditionally used to ameliorate inflammation and improve blood circulation. However, its role in platelet activation has not been thoroughly investigated. Hence, we conducted this study to assess the potential inhibitory effect of SA on platelet aggregation and thrombus formation. The antiplatelet activities of SA were evaluated by assessing platelet aggregation, granular secretion, intracellular Ca2+ mobilization, and the Glycoprotein (GP) VI-mediated signalosome. The thrombosis and bleeding time assays were used to investigate the effect of SA (orally administered at 50 and 100 mg/kg for seven days) in mice. SA treatment at concentrations of 50, 100, and 200 µg/mL significantly reduced GPVI-mediated platelet aggregation, granular secretion, and intracellular Ca2+ mobilization. Further biochemical studies revealed that SA inhibited spleen tyrosine kinase, phospholipase Cγ2, phosphatidylinositol 3-kinase, and AKT phosphorylation. Interestingly, oral administration of SA efficiently ameliorated FeCl3-induced arterial thrombus formation without prolonging the tail bleeding time. These findings suggest that SA has beneficial effects in thrombosis and hemostasis. Therefore, SA holds promise as an effective therapeutic agent for the treatment of thrombotic diseases.