Gastric cancer (GC) is a preventable disease, and Helicobacter pylori infection is the most important controllable risk factor. Despite numerous studies confirming that eradicating H. pylori can reduce the risk of GC, there remains a significant gap between the fundamental and clinical knowledge and public health interventions. This article provides a review of the progress made in the last decade by gastroenterologists in understanding the carcinogenic effects of H. pylori. The authors also summarize the evidence demonstrating the beneficial effects of eradication of H. pylori on gastric precancerous lesions and GC, and outline current strategies for H. pylori management. Notably, a family-based approach to H. pylori management represents a novel strategy for future GC prevention and control, boasting numerous advantages and having the potential to play a crucial role in future policymaking.

Exosomes are 60–120 nm diameter double-membrane lipid organelles discharged by cells. Various studies have shown that exosomes exert multiple functions in both physical and diseased processes, such as intercellular information exchange, immune response, and disease progression. Repeated chronic injury to the liver often leads to inflammation and liver fibrosis (LF), a disorder that, if unchecked, may progress to cirrhosis, liver failure, portal hypertension, and even hepatocellular carcinoma. As an essential component of host innate immunity against pathogen invasion, macrophages play an important role in modulating inflammation homeostasis by finely tuning the polarization process of macrophages into either M1 or M2 subtypes in response to different microenvironments. As a critical contributor to the inflammation process, macrophages also play a complex and instrumental function in the progression of LF. This review focuses on recent advancements in the role of macrophage-associated exosomes implicated in LF, including macrophage-released exosomes and macrophage-targeted exosomes. In addition, the progress made in exosome-based antifibrotic therapy by in vivo and in vitro studies is also highlighted.

Mixed phenotype acute leukemia (MPAL) is an uncommon acute leukemia, representing only 2–5% of acute leukemia cases. Extramedullary disease (EMD) is typically seen during a relapse or with disease progression. When EMD occurs in acute myeloid leukemia, it is called myeloid sarcoma. However, to the best of our knowledge, there are no reports of EMD in MPAL patients at the initial diagnosis. We provide the first case, which shows EMD associated with bone marrow necrosis of MPAL with minor BCR/ABL (BCR::ABL1 fusion gene) at disease onset. A 50-year-old Japanese man presented to a hematologist with a month-long history of immobility due to severe lumbar pain. Bone marrow aspirations were unsuccessful. Computed tomography revealed a mass in the left iliopsoas muscle and hepatosplenomegaly. He was diagnosed with MPAL associated with minor BCR/ABL, and EMD was confirmed by the analysis of blast phenotype in peripheral blood and necrotic bone marrow, as well as the biopsied mass in the iliopsoas muscle. He was first treated with cytarabine, then treatment was switched to a combination of steroids and dasatinib after the final diagnosis. The blast in peripheral blood disappeared, and the mass in the left iliopsoas shrunk one month after dasatinib treatment. Later bone marrow biopsy findings confirmed initial bone marrow necrosis. Although EMD associated with bone marrow necrosis at disease onset of MPAL with minor BCR/ABL is rare, our case underscores that no type of leukemia should be excluded from the differential diagnosis of bone marrow necrosis and EMD.

Coronary stenosis is responsible for angina attacks in coronary heart disease (CHD). A prospective pilot study was conducted to investigate the effects of combining remote ischemic preconditioning (RIPC) with Radix salviae decoction (RSD).

A total of 60 patients diagnosed with CHD were enrolled and divided into the control group and the RIPC-RSD treatment group. The primary outcome was the frequency of angina attacks, while the secondary outcomes included Canadian Cardiovascular Society levels, emergency medications, and prognosis indicators.

A total of 57 patients were included in the final analysis. Demographic characteristics and vessel stenosis comparisons showed similar results (p > 0.05). There was no significant difference in the frequency of angina attacks before (χ2 = 2.170, p = 0.404) or after (χ2 = 1.509, p = 0.662) treatment. Similarly, there was no significant difference in CCS levels of angina attacks between the two groups before (χ2 = 1.504, p = 0.681) or after (χ2 = 1.392, p = 0.707) treatment. Although there was no significant difference in the use of emergency medications for angina attacks before (χ2 = 1.321, p = 0.517) or after (χ2 = 2.457, p = 0.356) treatment, a significant decrease in the frequency of emergency medications was observed (Z = −2.188, p = 0.029). However, the RIPC-RSD treatment did not have a significant impact on the prognosis (cardiac death, χ2 = 1.831, p = 0.176; target vessel revascularization, χ2 = 1.111, p = 0.292; rehospitalization, χ2 = 0.495, p = 0.482) of coronary stenosis in CHD patients.

Due to the limitations of a relatively small sample size, this prospective pilot study did not observe a significant effect of RIPC-RSD on angina attacks and prognosis in CHD patients, but it implied potential efficacy in reducing the frequency of emergency medications.

Various risk engines exist for predicting future cardiovascular disease. We developed a noninvasive cardiovascular disease risk app which appeared to work well for us without need for invasive tests. This is an attempt to compare its predictive accuracy with an already existing widely used risk engine.

We used data partly generated in our earlier study on resistant hypertension. Between May and October 2021, those who were still attending care had abdominal height, blood pressure, weight, and height measured. Body surface index was derived from height and weight. Information on sex, family history of cardiovascular disease, alcohol use, physical inactivity, smoking, and diabetes history, total, and high-density lipoprotein cholesterol was extracted from the records. Data as appropriate were imputed into our new app and the atherosclerotic cardiovascular disease risk estimator app of the American Heart Association. The results were compared.

Fifty-two patients with complete data were studied. Both methods strongly correlated positively (R = 0.805, p = 0.000), showing equivalence. Risk levels determined by both methods agreed on high cardiovascular disease risk in 21(40.30%) and intermediate risk in 22 (42.31%) patients. Four patients were classified as high risk and as medium risk by the established American Heart Association app. Five were at intermediate risk with our app and at low risk with the American Heart Association app.

In 43 cases (82.69%), both tools agreed on cardiovascular disease risk prediction. In nine there was a tendency for the American Heart Association app to put patients in a lower risk category. This tends to delay the initiation of appropriate preventive or curative measures. Given the total dependence on anthropometric and historical indices, it is felt that our new method is cheaper and should be more widely deployed in preventive cardiology.

There has been a recent increase in the incidence of allergies and the severity of allergic reactions worldwide. Most allergy treatments, such as antihistamines, only treat the symptoms of the allergy. In contrast, allergen-specific immunotherapy (ASIT) refers to a pathogenetic treatment that prevents the progression of allergies. ASIT can also reduce the risk of mild reactions, such as allergic rhinitis, worsening into more serious conditions, such as allergic bronchial asthma. ASIT is performed by administration of an allergen, usually either subcutaneously or sublingually. Sublingual administration is regarded as safer than subcutaneous administration because of a reduction in the risks associated with systemic effects. The uptake of allergens by the mucous membranes in sublingual administration can be improved using delivery agents, such as liposomes, dendrimers, and nanoparticles. Glycyrrhizic acid can self-associate to form micelles and thus, form complexes to enable the delivery of poorly soluble drugs. In addition, glycyrrhizic acid has been shown to have anti-inflammatory effects and is itself a potential treatment for allergic diseases such as allergic rhinitis and asthma. Thus, the development of an ASIT using glycyrrhizic acid is of interest. Herein, we review allergic bronchial asthma and allergic rhinitis and the use of ASIT in the treatment of these conditions. We then discuss glycyrrhizic acid and the potential development of delivery agents using glycyrrhizic acid for use in ASIT.

Ophiocordyceps sinensis is widely used in traditional Asian medicine and grows at high altitudes (3,000–4,000 meters) on the Qinghai-Tibet Plateau. This fungus is an expensive and rare species that is difficult to cultivate. Increasing global demand, limited commercial trade, and precious resources drive an urgent need for the development of artificial cultivation techniques to produce bioactive compounds. This paper reviews the genome biology, culture systems, solid-state and submerged fermentation processes used to produce bioactive compounds in O. sinensis. It also elucidates its biological properties at the genome level for the development of synthetic media. We performed a bibliometric analysis, retrieving information on various aspects of this fungus from NCBI PubMed. A total of 135 research articles on O. sinensis were collected, of which 104 focused on the production of bioactive compounds and 26 focused on ‘x-omics’ studies. Next-generation sequencing data provides a genetic basis for fungal biology and host specificity. Recent developmental transcriptomic studies described mechanisms underlying the transcriptional regulation of fruiting body development and cold adaptation. Metabolic data indicate that many bioactive compounds are produced by cultured mycelia or fruiting bodies. The biological properties of this fungus can be used to design and develop synthetic media for fruiting body development and enhance the production of bioactive compounds. Several bioactive compounds and their pharmacological properties have been studied in the mycelia and culture supernatants. Since cultured O. sinensis is an alternative to natural and cultured C. militaris strains, research on the design and formulation of solid media for the production of fruiting bodies and bioactive compounds is currently attracting attention.

Peroxisome proliferator-activated receptors (PPARs) are a superfamily of nuclear transcription receptors, consisting of PPARα, PPARγ, and PPARβ/δ, which are highly expressed in the liver. They control and modulate the expression of a large number of genes involved in metabolism and energy homeostasis, oxidative stress, inflammation, and even apoptosis in the liver. Therefore, they have critical roles in the pathophysiology of hepatic diseases. This review provides a general insight into the role of PPARs in liver diseases and some of their agonists in the clinic.

Achieving and maintaining quality is of utmost importance in laboratory operations for the best possible patient care. The concepts of quality control and related quality procedures and programs are relatively new and less well understood in histopathology laboratories than in other sections of clinical laboratories, particularly in developing countries. This is because the main product from these laboratories consists of descriptive, opinion-based reports rather than numerical reports as in other fields of laboratory medicine, and most of the work is still manual and involves multiple steps. The scope and extent of quality schemes in histopathology laboratories are very broad and complex, requiring coordinated and concerted efforts on the part of all stakeholders to achieve and maintain quality services in these laboratories. There is a need to create awareness among the pathologist community and other healthcare members about the necessity of quality assurance and improvement schemes in these laboratories to achieve optimal patient care. This paper reviewed the scope and extent of quality schemes in histopathology laboratories.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a unique type of liver tumor that contains both hepatocellular carcinoma and cholangiocarcinoma components within a single tumor. The fifth edition of the World Health Organization classification provides a definition and diagnostic criteria for cHCC-CCA. However, the heterogeneous histomorphology and presentation resulting from variation of the proportion of each component poses challenges for clinical diagnosis and treatment. A diagnosis of cHCC-CCA may be suggested by the synchronous elevation of serum tumor markers for hepatocellular carcinoma and cholangiocarcinoma, a mixed enhancement pattern on imaging, and a discrepancy between the elevation of tumor marker and the imaging enhancement pattern. Histopathological examination using hematoxylin and eosin staining is considered the gold standard for diagnosing cHCC-CCA, and comprehensive examination of resection or biopsy specimens is crucial for an accurate diagnosis. Currently, there is no standard treatment for cHCC-CCA, and surgery is the mainstay. Anatomic hepatectomy with lymphadenectomy is among the recommended surgical procedures. The role of liver transplantation in the management of cHCC-CCA is still uncertain. Transarterial chemoembolization may be effective for unresectable cHCC-CCA, particularly for hypervascular tumors. However, the available evidence does not support systemic therapy for advanced cHCC-CCA. The prognosis of cHCC-CCA is generally poor, and there is no established staging system. Further research is needed to better understand the histogenesis and clinical management of cHCC-CCA. This review provides an overview of the current literature on cHCC-CCA with a focus on its clinical characteristics, pathological diagnosis, and management.

Melanoma has become a severe burden for human beings, with high mortality and a growing incidence. Currently, various nanomedicines integrated with novel therapeutic strategies and precision delivery have been developed to treat melanoma. Although great achievements have been made in the development of nanomedicines, clinical translation is lagging far behind. In this review, three research questions are raised to elucidate the bibliometric study on nanomedicines as melanoma therapeutics. The basic bibliometric properties are presented and analyzed. International cooperation and research foci are emphasized. Finally, future research directions for nanomedicines to promote clinical translation are raised, and several feasible suggestions are proposed. We believe that this review could serve as a guideline document for the development of nanomedicines for melanoma therapeutics.

As sepsis progresses, immune cell apoptosis plays regulatory roles in the pathogenesis of immunosuppression and organ failure. We previously reported that adenosine deaminases acting on RNA-1 (ADAR1) reduced intestinal and splenic inflammatory damage during sepsis. However, the roles and mechanism of ADAR1 in sepsis-induced liver injury remain unclear.

We performed transcriptome and single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with sepsis to investigate the effects of ADAR1 on immune cell activities. We also employed a cecal ligation and puncture (CLP) sepsis mouse model to evaluate the roles of ADAR1 in sepsis-induced liver injury. Finally, we treated murine RAW 264.7 macrophages with lipopolysaccharide to explore the underlying ADAR1-mediated mechanisms in sepsis.

PBMCs from patients with sepsis had obvious apoptotic morphological features. Single-cell RNA sequencing indicated that apoptosis-related pathways were enriched in monocytes, with significantly elevated ADAR1 and BCL2A1 expression in severe sepsis. CLP-induced septic mice had aggravated liver injury and Kupffer cell apoptosis that were largely alleviated by ADAR1 overexpression. ADAR1 directly bound to pre-miR-122 to modulate miR-122 biosynthesis. miR-122 was an upstream regulator of BCL2A1. Furthermore, ADAR1 also reduced macrophage apoptosis in mice with CLP-induced sepsis through the miR-122/BCL2A1 signaling pathway and protected against sepsis-induced liver injury.

The findings show that ADAR1 alleviates macrophage apoptosis and sepsis-induced liver damage through the miR-122/BCL2A1 signaling pathway. The study provides novel insights into the development of therapeutic interventions in sepsis.

Liver fibrosis is a reversible condition that occurs in the early stages of chronic liver disease. To develop effective treatments for liver fibrosis, understanding the underlying mechanism is crucial. The NOD-like receptor protein 3 (NLRP3) inflammasome, which is a part of the innate immune system, plays a crucial role in the progression of various inflammatory diseases. NLRP3 activation is also important in the development of various liver diseases, including viral hepatitis, alcoholic or nonalcoholic liver disease, and autoimmune liver disease. This review discusses the role of NLRP3 and its associated molecules in the development of liver fibrosis. It also highlights the signal pathways involved in NLRP3 activation, their downstream effects on liver disease progression, and potential therapeutic targets in liver fibrosis. Further research is encouraged to develop effective treatments for liver fibrosis.

As a subunit of the condensin complex, NCAPG has an important role in maintaining chromosome condensation, but its biological function and regulatory mechanism in hepatocellular carcinoma (HCC) remains undefined.

The prognostic ability of NCAPG in HCC patients was examined by univariate and multivariate Cox regression analysis. ROC curves were plotted to compare the predictive ability of NCAPG and AFP. Double luciferase reporter system, and ChIP were used to investigate transcriptional potential of E2F1 to NCAPG. Pyroptosis was observed by scanning electron microscopy. Protein expression of NCAPG, E2F1, and major proteins constituting NLRP3 inflammasome was determined by western blotting and ELISA. An in vivo tumor formation assay was conducted to verify the in vitro results.

Up-regulated NCAPG was identified in HCC tissues compared with adjacent tissue and high NCAPG was positively correlated with poor prognosis. Serum NCAPG mRNA level was a prognostic factor in HCC patients and also a diagnostic factor with higher predictive ability compared with AFP [AUROC 0.766 (95% CI: 0.650–0.881) vs. 0.649 (95% CI 0.506–0.793)]. HBx transfection resulted in concomitant up-regulation of E2F1 and NCAPG. E2F1 significantly increased the activity of luciferase reporter fused with NCAPG reporter, and the interaction of E2F1 and NCAPG gene was confirmed by ChIP. Silencing of E2F1 resulted in significant down-regulation of NCAPG. Knockdown of NCAPG promote pyroptosis mediated by NLRP3 inflammasome activation in multiple HCC cell lines and also suppressed tumorigenesis in vitro.

We identified a novel role of NCAPG in the regulation of NLRP3 inflammasome-mediated pyroptosis, which was regulated by its upstream transactivator, E2F1. The role of E2F1-NCAPG-NLRP3 regulation of pyroptosis network may be a potential target in HCC treatment.

No previous study has been conducted in Nigeria on the role of neutrophil elastase in predicting preterm birth. The present study aimed to determine the role of the neutrophil elastase test in predicting birth in women with preterm labor.

The present prospective cohort study recruited 83 pregnant women with preterm labor between 28 and 36+6 weeks of gestation, and followed up these subjects for 14 days. The controls comprised 85 pregnant women without preterm labor. The cervicovaginal fluid was collected and tested using the neutrophil elastase test. Then, the sensitivity, specificity, and positive and negative predictive parameters were determined. Afterward, the data were scrutinized using the SPSS arithmetic software (Sort23).

Among the 168 pregnant women analyzed in the present study, 83 pregnant women were assigned to the preterm labor group, and 85 pregnant women were assigned to the control group. Furthermore, among the 83 pregnant women in the preterm labor group, 11 women had spontaneous preterm delivery, leading to a spontaneous preterm birth proportion of 13.3%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the neutrophil elastase test within 14 days post-enrollment were 93.8%, 61.2%, 36.6%, 97.6%, and 67.5%, respectively, for the general population, and 87.5%, 66.7%, 35.0%, 96.3%, and 70.2%, respectively, for subjects at <35 weeks of gestation. The positive and negative likelihood ratios for preterm birth prediction were 2.62 and 0.19, respectively.

The neutrophil elastase test exhibited high predictive accuracy in pregnant women with preterm labor, when compared to the controls, based on the sensitivity and negative predictive value, but this had poor positive predictive values. The neutrophil elastase test may be used as a screening test, but not as a potential predictive test, in the routine clinical setting.

Hypoxia-inducible factor-1 alpha (HIF-1α) is usually regarded as a core regulator of hypoxic response. Persistent inflammation and impaired wound healing are common manifestations of diabetic foot ulcer (DFU). In normal wounds, HIF-1α and its related regulatory molecules, such as vascular endothelial growth factor and inducible nitric oxide synthase, are activated by hypoxia signals, which in turn promote wound healing. However, abnormal regulation of the HIF-1α signaling pathway by hyperglycemia leads to impaired wound healing in DFU. In this review, we highlight the tissue-specific and stage-specific effects of the HIF-1α signaling pathway in DFU. In the early stage of DFU, HIF-1α in inflammatory cells is over-upregulated by hyperglycemia, causing the activation of nuclear factor-κB and the inducible nitric oxide synthase-mediated pro-inflammatory signaling pathway, leading to sustained inflammation, which is deleterious. In the late stage of DFU, HIF-1α in endothelial cells and keratinocytes is inhibited by hyperglycemia, which leads to the downregulation of vascular endothelial growth factor expression, resulting in insufficient angiogenesis and difficult healing at the wound site. In this review, we discuss recent advances in the knowledge of the HIF-1α signaling pathway and the key targeted molecules in impaired wound healing of DFU. We also summarize the drugs currently in clinical trials that target HIF-1α or its downstream molecules, recapitulate current gaps in our knowledge, and propose rational therapeutic strategies for DFU based on the action characteristics of HIF-1α.

We previously reported that transforming growth factor-beta 1 (TGF-β1) promoted breast cancer progression and metastasis through inhibiting the expression of miR-4638-3p via directly targeting activating transcription factor 3 (ATF3). The present study aimed to elucidate the mechanisms of TGF-β1 downregulating ATF3 targeting miR-4638-3p via circRNA in MDA-MB231 cells.

Three triple-negative human breast cancer cells (MDA-MB231, MDA-MB468, and MDA-MB453) were employed. In-silico analyses were used to identify the list of circRNAs targeting miR-4638-3p. RT-qPCR was performed to determine the expression of shortlisted circRNAs. Transient transfection and western blot analyses were carried out to identify the functional role of circ_DISP3. A dual-luciferase reporter assay was used to identify the direct binding of circ_DISP3 and miR-4638-3p.

There was an inverse correlation between the expression of circ_DISP3 and miR-4638-3p in these cells. Antisense oligos-mediated silencing of circ_DISP3 restored the function of miR-4638-3p, and downregulated ATF3 in MDA-MB231 cells. The luciferase reporter assay identified the direct binding of circ_DISP3 to miR-4638-3p in these cells.

TGF-β1 influences the expression of ATF3 to stimulate circ_DISP3 to sponge miR-4638-3p in hBC cells. Hence, we suggest that the circ_DISP3/miR-4638-3p/ATF3 axis regulated by TGF-β1 may have potential applications for bone-metastatic breast cancer.