Clarifying varied Helicobacter pylori eradication therapies: A comprehensive review.

Current global variations exist in Helicobacter pylori (H. pylori) eradication regimens. Triple therapy (TT), bismuth quadruple therapy (BQT), and high-dose dual therapy (HDDT) currently represent the predominant regimens. These regimens diverge in terms of treatment duration, the utilization of susceptibility testing, acid-inhibiting drug administration, and patient education. We conducted a comprehensive systematic literature review on these H. pylori treatment regimens. Our review aims to provide standardized treatment recommendations for H. pylori, reducing the risk of amalgamating findings from diverse eradication regimens. Recent research suggests that the optimal treatment duration for TT and BQT may be 14 and 10 days, respectively. Selecting the appropriate treatment duration for HDDT should rely on regional research evidence, and 14 days may be the optimal duration. The incorporation of susceptibility testing in TT is of paramount importance. In the case of BQT, the absence of susceptibility testing may be considered as an option, contingent upon cost and availability, and should be determined based on local antibiotic resistance patterns and the efficacy of empirical regimens. The type and dosage of acid-inhibiting drug would affect the efficacy of these regimens. Acid-inhibiting drugs should be selected and applied reasonably according to the population and therapies. Adequate patient education plays a pivotal role in the eradication of H. pylori. In regions with accessible local research evidence, the 10-day empirical BQT regimen may be considered a preferred choice for H. pylori eradication.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Cleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms.

Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins, activated by proteolytic removal of the inhibitory domain. Here we report two types of cleavage-independent GSDM activation. First, TrichoGSDM, a pore-forming-domain-only protein from the basal metazoan Trichoplax adhaerens, is a disulfides-linked autoinhibited dimer, activated by reduction of the disulfides. Cryo-electron microscopy (cryo-EM) structure illustrates assembly mechanism for the 44-mer TrichoGSDM pore. Second, RCD-1-1/RCD-1-2, encoded by polymorphic rcd-1 in filamentous fungus Neurospora crassa, are also pore-forming-domain-only GSDMs. RCD-1-1 and RCD-1-2, when encountering each other, form pores and cause pyroptosis, underlying allorecognition in Neurospora. Cryo-EM structure reveals a pore of 11 RCD-1-1/RCD-1-2 heterodimers and heterodimerization-triggered pore assembly mechanism. This study shows mechanistic diversities in GSDM activation and indicates versatile functions of GSDMs.

A comprehensive N-glycome map of porcine sperm membrane before and after capacitation.

Mapping the N-glycome of porcine sperm before and after sperm capacitation is important for understanding the rearrangement of glycoconjugates during capacitation. In this work, we characterized the N-glycome on the membranes of 18 pairs of fresh porcine sperm before capacitation and porcine sperm after capacitation by MALDI-MS (Matrix-assisted laser desorption/ionization-mass spectrometry). A total of 377 N-glycans were detected and a comprehensive N-glycome map of porcine sperm membranes before and after capacitation was generated, which presents the largest N-glycome dataset of porcine sperm cell membranes. Statistical analysis revealed a significantly higher level of high mannose glycosylation and a significantly lower level of fucosylation, galactosylation, and α-2,6-NeuAc after capacitation, which is further verified by flow cytometry and lectin blotting. This research reveals new insights into the relationship between N-glycosylation variations and sperm capacitation, including the underlying mechanisms of the capacitation process.

Alnustone promotes megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway.

OBJECTIVES: Thrombocytopenia is a disease in which the number of platelets in the peripheral blood decreases. It can be caused by multiple genetic factors, and numerous challenges are associated with its treatment. In this study, the effects of alnustone on megakaryocytes and platelets were investigated, with the aim of developing a new therapeutic approach for thrombocytopenia. METHODS: Random forest algorithm was used to establish a drug screening model, and alnustone was identified as a natural active compound that could promote megakaryocyte differentiation. The effect of alnustone on megakaryocyte activity was determined using cell counting kit-8. The effect of alnustone on megakaryocyte differentiation was determined using flow cytometry, Giemsa staining, and phalloidin staining. A mouse model of thrombocytopenia was established by exposing mice to X-rays at 4 Gy and was used to test the bioactivity of alnustone in vivo. The effect of alnustone on platelet production was determined using zebrafish. Network pharmacology was used to predict targets and signaling pathways. Western blotting and immunofluorescence staining determined the expression levels of proteins. RESULTS: Alnustone promoted the differentiation and maturation of megakaryocytes in vitro and restored platelet production in thrombocytopenic mice and zebrafish. Network pharmacology and western blotting showed that alnustone promoted the expression of interleukin-17A and enhanced its interaction with its receptor, and thereby regulated downstream MEK/ERK signaling and promoted megakaryocyte differentiation. CONCLUSIONS: Alnustone can promote megakaryocyte differentiation and platelet production via the interleukin-17A/interleukin-17A receptor/Src/RAC1/MEK/ERK signaling pathway and thus provides a new therapeutic strategy for the treatment of thrombocytopenia.

Case report: Treatment of psoriasiform dermatitis in patients with malignancy.

Psoriasis and atopic dermatitis (AD) are prevalent inflammatory skin disorders, each stemming from diverse factors, and characterized by recurring episodes. In certain complex cases, the clinical and pathological features exhibit overlapping and atypical characteristics, making accurate clinical diagnosis and targeted treatment a challenge. Psoriasiform dermatitis is the term used to describe such cases. Moreover, when patients have a history of malignancy, the situation becomes even more intricate, resulting in limited treatment options. Biologic therapies have transformed the management of immune-mediated inflammatory diseases, including psoriasis and AD. Meanwhile, the safety of biologics in special populations, especially among patients with a history of malignancy, should be underlined. The selective Janus kinase 1 (JAK1) inhibitor abrocitinib has been approved for the treatment of AD and has showed satisfying efficacy and safety in the treatment of psoriasis in clinical trials. Although unreported, JAK1 inhibitors are thought to have the potential to increase the risk of potential tumors. Apremilast, an oral phosphodiesterase (PDE)-4 inhibitor, is approved for moderate to severe plaque psoriasis. It has been investigated for its efficacy in AD, and is not contraindicated in malignancy. This report presents three cases of psoriasiform dermatitis in patients with a history of malignancy, showcasing significant improvement following treatment with systemic glucocorticoid, abrocitinib, or apremilast.

Serum N-glycomic profiling identifies candidate biomarker panels for assessing coronary artery stenosis severity.

Stenosis severity may escalate over the course of coronary artery disease (CAD), increasing the risk of death for the patient. Conventionally, the assessment of stenosis degree relies on invasive coronary angiography (ICA), an invasive examination unsuitable for patients in poor physical condition or those with contrast allergies and one that imposes a psychological burden on patients. Although abnormal serum N-glycan profiles have exhibited robust associations with various cardiovascular diseases, including CAD, their potential in diagnosing CAD stenosis remains to be determined. In this study, we performed a comprehensive analysis of serum N-glycome from 132 patients who underwent ICA and 27 healthy controls using MALDI-TOF-mass spectrometry. The patients who underwent ICA examination were categorized into four groups based on stenosis severity: no/mild/moderate/severe stenosis. Twenty-seven N-glycans were directly quantified, and 47 derived glycan traits were obtained. Notably, among these 74 glycan features, 18 exhibited variations across the study groups. Using a combination of least absolute shrinkage and selection operator and logistic regression analyses, we developed five diagnostic models for recognizing stenosis degree. Our results suggested that alterations in serum N-glycosylation modifications might be valuable for identifying stenosis degree and monitoring disease progression in individuals with CAD. It is expected to offer a noninvasive alternative for those who could not undergo ICA because of various reasons. However, the diagnostic potential of serum N-glycan panels as biomarkers requires multicenter, large cohort validation in the future.

O-GlycoIsoQuant: A Novel O-Glycome Quantitative Approach through Superbase Release and Isotopic Girard's P Labeling.

Quantitative glycosylation analysis serves as an effective tool for detecting changes in glycosylation patterns in cancer and various diseases. However, compared with N-glycans, O-glycans present challenges in both qualitative and quantitative mass spectrometry analysis due to their low abundance, ease of peeling, lack of a universal enzyme, and difficult accessibility. To address this challenge, we developed O-GlycoIsoQuant, a novel O-glycome quantitative approach utilizing superbase release and isotopic Girard's P labeling. This method facilitates rapid and efficient nonreducing ß-elimination to dissociate O-glycans from proteins using the organic superbase, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), combined with light and heavy isotopic Girard's reagent P (GP) labeling for relative quantification of O-glycans by mass spectrometry. Employing this method, labeled O-glycans exhibit a double peak with a mass difference of 5 Da, suitable for stable relative quantification. The O-GlycoIsoQuant method is characterized by its high labeling efficiency, excellent reproducibility (CV < 20%), and good linearity (R2 > 0.99), across a dynamic range spanning a 100-fold range. This method was applied to various complex sample types, including human serum, porcine spermatozoa, human saliva, and urinary extracellular vesicles, detecting 33, 39, 49, and 37 O-glycans, respectively, thereby demonstrating its broad applicability.

Pd@Pt Core-Shell Nanocrystal-Decorated ZnO Nanosheets for ppt-Level NO2 Detection.

Bimetallic nanocrystals (NCs) have obtained significant attention due to their unique advantages of the intrinsic properties of individual metals and synergistic enhancements resulting from the electronic coupling between two constituent metals. In this work, Pd@Pt core-shell NCs were prepared through a facile one-pot solution-phase method, which had excellent dispersion and uniform size. Concurrently, ZnO nanosheets were prepared via a hydrothermal method. To explore their potential in nitrogen dioxide (NO2) gas sensing applications, sensitive materials based on ZnO nanosheets with varying mass percentages of Pd@Pt NCs were generated through an impregnation process. The sensor based on 0.3 wt % Pd@Pt-ZnO exhibited remarkable performance, demonstrating a substantial response (Rg/Ra = 60.3) to 50 ppb of NO2 at a low operating temperature of 80 °C. Notably, this sensor reached an outstanding low detection limit of 300 ppt. The enhancement in gas sensing capabilities can be attributed to the sensitization and synergistic effects imparted by the exceptional catalytic activity of Pd@Pt NCs, which significantly promoted the reaction. This research introduces a novel approach for the utilization of core-shell structured bimetallic nanocrystals as modifiers in metal-oxide-semiconductor (MOS) materials for NO2 detection.

Health information in short videos about metabolic dysfunction-associated steatotic liver disease: Analysing quality and reliability.

BACKGROUND & AIMS: Short videos, crucial for disseminating health information on metabolic dysfunction-associated steatotic liver disease (MASLD), lack a clear evaluation of quality and reliability. This study aimed to assess the quality and reliability of MASLD-related videos on Chinese platforms. METHODS: Video samples were collected from three platforms (TikTok, Kwai and Bilibili) during the period from November 2019 to July 2023. Two independent reviewers evaluated the integrity of the information contained therein by scoring six key aspects of its content: definition, epidemiology, risk factors, outcomes, diagnosis and treatment. The quality and reliability of the videos were assessed using the Journal of the American Medical Association (JAMA) criteria, the Global Quality Score (GQS) and the modified DISCERN score. RESULTS: A total of 198 videos were included. The video content exhibited an overall unsatisfactory quality, with a primary emphasis on risk factors and treatment, while diagnosis and epidemiology were seldom addressed. Regarding the sources of the videos, the GQS and modified DISCERN scores varied significantly between the platforms (p = .003), although they had generally similar JAMA scores (p = .251). Videos created by medical professionals differed significantly in terms of JAMA scores (p = .046) compared to those created by nonmedical professionals, but there were no statistically significant differences in GQS (p = .923) or modified DISCERN scores (p = .317). CONCLUSIONS: The overall quality and reliability of the videos were poor and varied between platforms and uploaders. Platforms and healthcare professionals should strive to provide more reliable health-related information regarding MASLD.

An Innovative Inducer of Platelet Production, Isochlorogenic Acid A, Is Uncovered through the Application of Deep Neural Networks.

(1) Background: Radiation-induced thrombocytopenia (RIT) often occurs in cancer patients undergoing radiation therapy, which can result in morbidity and even death. However, a notable deficiency exists in the availability of specific drugs designed for the treatment of RIT. (2) Methods: In our pursuit of new drugs for RIT treatment, we employed three deep learning (DL) algorithms: convolutional neural network (CNN), deep neural network (DNN), and a hybrid neural network that combines the computational characteristics of the two. These algorithms construct computational models that can screen compounds for drug activity by utilizing the distinct physicochemical properties of the molecules. The best model underwent testing using a set of 10 drugs endorsed by the US Food and Drug Administration (FDA) specifically for the treatment of thrombocytopenia. (3) Results: The Hybrid CNN+DNN (HCD) model demonstrated the most effective predictive performance on the test dataset, achieving an accuracy of 98.3% and a precision of 97.0%. Both metrics surpassed the performance of the other models, and the model predicted that seven FDA drugs would exhibit activity. Isochlorogenic acid A, identified through screening the Chinese Pharmacopoeia Natural Product Library, was subsequently subjected to experimental verification. The results indicated a substantial enhancement in the differentiation and maturation of megakaryocytes (MKs), along with a notable increase in platelet production. (4) Conclusions: This underscores the potential therapeutic efficacy of isochlorogenic acid A in addressing RIT.

Arenobufagin modulation of PCSK9-mediated cholesterol metabolism induces tumor-associated macrophages polarisation to inhibit hepatocellular carcinoma progression.

BACKGROUND: The tumor microenvironment (TME) of hepatocellular carcinoma is heterogeneous enough to be prone to drug resistance and multidrug resistance during treatment, and reprogramming of cholesterol metabolism in TME mediates tumor-associated macrophages (TAMs) polarization, which has an impact on the regulation of malignant tumor progression. Arenobufagin (ARBU) was extracted and isolated from toad venom (purity ≥98 %), which is the main active ingredient of the traditional Chinese medicine Chan'su with good anti-tumor effects. PURPOSE: To investigate the regulatory effect of ARBU on lipid metabolism in tumor microenvironment, interfere with macrophage polarization, and determine its mechanism of action on liver cancer progression. METHODS: In this study, the inhibitory effect of ARBU on the proliferation of Hepa1-6 in C57 mice and the safety of administration were evaluated by establishing a transplanted tumor model of Hepa1-6 hepatocellular carcinoma mice and using 5-FU as a positive control drug. In addition, we constructed a co-culture system of Hepa1-6 cells and primary mouse macrophages to study the effects of ARBU on the polarization phenotypic transformation of macrophages and the proliferation and migration of hepatoma cells. The influence of ARBU on the metabolism of lipids in the hepatocellular carcinoma mouse model was investigated by combining it with lipidomics technology. The influence of ARBU on the PCSK9/LDL-R signaling pathway and macrophage polarization, which regulate cholesterol metabolism, was tested by using qRT-PCR, gene editing, IF, and WB. CONCLUSION: ARBU significantly inhibited the proliferation of Hepa1-6 in vivo and in vitro, regulated cholesterol metabolism, and promoted the M1-type polarization of macrophages in the tumor microenvironment. ARBU inhibits cholesterol synthesis in the TME through the PCSK9/LDL-R signaling pathway, thereby blocking macrophage M2 polarization, promoting apoptosis of the tumor cells, and inhibiting their proliferation and migration.

Corrigendum to "Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway" [Heliyon 9(7) (July 2023) e17841].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17841.].

Individualized small bowel preparation for computed tomography enterography: A prospective randomized controlled trial.

BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2 , 1500 mL for patients with 18.5 kg/m2  ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2 ) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2 , 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2 , 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.

Overexpression of Nrf2 reverses ferroptosis induced by Arenobufagin in gastric cancer.

Arenobufagin (ArBu) is a natural monomer extracted and isolated from the secretion of the Chinese toad, also known as toad venom. This compound exerts anti-tumor effects by promoting apoptosis in tumor cells, inhibiting tumor angiogenesis, and preventing the invasion and migration of tumor cells. However, their impact on ferroptosis in tumor cells has yet to be fully confirmed. In this study, we established a subcutaneous transplant tumor model in nude mice to investigate the inhibitory effect of ArBu on gastric cancer cells (MGC-803) and the safety of drug delivery. in vitro experiments, we screened the most sensitive cancer cell lines using the MTT method and determined the response of ArBu to cell death. Use flow cytometry to measure cytoplasmic and lipid reactive oxygen species (ROS) levels. Determine the expression levels of ferritin-related proteins through Western blot experiments. In addition, a MGC-803 cell model overexpressing Nrf2 was created using lentiviral transfection to investigate the role of ArBu in inducing ferroptosis in cancer cells. Our research findings indicate that ArBu inhibits the proliferation of MGC-803 cells and is linked to ferroptosis. In summary, our research findings indicate that ArBu is a potential anti-gastric cancer drug that can induce ferroptosis in human cancer cells through the Nrf2/SLC7A11/GPX4 pathway.

Influence of subcutaneous adipose tissue index on prognosis in cirrhotic patients following endoscopic therapy: a retrospective cohort study.

BACKGROUND: The relation of adipose tissue depletion with prognostic outcome of variceal bleeding among cirrhotic patients is still inconclusive. The present work explored whether adipose tissue, which was measured based on computed tomography (CT), was valuable for analyzing rebleeding and mortality among patients with variceal bleeding who had undergone endoscopic therapy. METHODS: The study encompassed cirrhotic patients who underwent endoscopic therapy to prevent variceal rebleeding between January 2016 and October 2022. The L3-level CT images were obtained. Besides, impacts of subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), as well as total adipose tissue index (TATI) on rebleeding and mortality among cirrhotic patients following endoscopic therapy were examined. RESULTS: In this work, our median follow-up period was 31 months. Among those adipose tissue indexes, only SATI exhibited an independent relation to higher rebleeding (HR 0.981, 95% CI, 0.971-0.991, p < 0.001) and mortality (HR 0.965, 95% CI, 0.944-0.986, p = 0.001) risks. Upon multivariate Cox regression, low SATI (male < 30.15 cm2/m2, female < 39.82 cm2/m2) was independently linked to higher rebleeding risk (HR 2.511, 95% CI, 1.604-3.932, p < 0.001) and increased mortality risk (HR 3.422, 95% CI, 1.489-7.864, p = 0.004) after adjusting for other predictors. Furthermore, subgroups were created based on using nonselective ß-blockers (NSBBs), demonstrating that quantitatively assessing SATI exerts a vital role in evaluating rebleeding incidence in patients with or without NSBB therapy. CONCLUSION: This study underscores the potential of quantifying SATI as a means for achieving a more accurate risk classification for individual patients and identifying patients that can gain more benefits from nutritional intervention.

Clinical, Diagnostic, and Treatment Characteristics of Orbital Liposarcoma.

PURPOSE: To clarify the clinical, diagnostic, and treatment characteristics of orbital liposarcoma. DESIGN: Retrospective observational case series. METHODS: A review was performed of electronic medical records, histopathology, radiological images, and follow-up information for 21 patients with orbital liposarcoma. RESULTS: The predominant clinical manifestation of this disease was painless exophthalmos. The most frequently encountered pathological types were well-differentiated and myxoid liposarcoma. Preoperative radiological images from 15 patients showed that orbital liposarcoma initially developed in extraocular muscle in 9 patients. Furthermore, all well-differentiated liposarcomas exhibited the radiographic characteristics of irregular and ill-defined adipose tissue, whereas only 12.5% of myxoid liposarcomas had the imaging characteristics. For the patients who exclusively underwent surgery, all of those with subtotal excisions experienced recurrence, 63.6% of marginal excisions recurred, and 50% of wide excisions resulted in recurrence. However, none of the patients who underwent marginal excisions or wide excisions combined with adjuvant radiotherapy exhibited recurrence. The analysis of magnetic resonance imaging findings in 3 patients who underwent neoadjuvant radiotherapy revealed that the tumor size remained stable in a patient with well-differentiated liposarcoma, whereas another patient with the same type of tumor exhibited a gradual increase in size. Conversely, a patient with myxoid liposarcoma experienced a significant reduction in tumor size following neoadjuvant radiotherapy. CONCLUSION: Orbital liposarcoma demonstrated a propensity for developing in the extraocular muscle. The radiological images of orbital well-differentiated liposarcomas were characterized by irregular and ill-defined adipose tissue. Surgery combined with radiotherapy demonstrated potential in reducing recurrence rates. Notably, orbital myxoid liposarcoma exhibited greater sensitivity to radiotherapy compared to well-differentiated liposarcoma.