Clinical factors associated with invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: analysis of a 6-year clinical experience.

Background: Invasive pulmonary aspergillosis (IPA) typically occurs in immunocompromised individuals. Severe fever with thrombocytopenia syndrome (SFTS) patients are typically characterized by fever, thrombocytopenia, and leukopenia. These patients typically present with dysregulation of cellular and humoral immunity, which may predispose them to IPA. Our study aimed to identify risk factors for SFTS-associated invasive pulmonary aspergillosis (SAPA) and evaluate its associated prognostic impact. Methods: We conducted a cohort study between January 2017 and December 2022 in a tertiary hospital in Wuhan City, China. All SFTS patients hospitalized in our department who formally consented were divided into a SAPA group and a non-SAPA group according to whether they were coinfected with aspergillosis or not. The independent risk factors for the SAPA group were determined by multivariate logistic regression. Receiver operating characteristic (ROC) analysis was used to assess the statistical value of parameters to predict SAPA patients. The survival analysis was carried out using the Kaplan-Meier (KM) method. Results: Of the 269 hospitalized SFTS patients enrolled in the study, 118 (43.87%) cases were diagnosed with SAPA with an average age of 65.71 ± 9.7 years. Multivariate logistic regression analysis revealed that age, neurological complications, serum severe fever with thrombocytopenia syndrome virus (SFTSV) RNA loads, the white blood cell (WBC) count, platelet (PLT) count, albumin (ALB) and globulin (GLB) concentrations, and cardiac troponin I (cTNI) were complementary risk factors for the development of IPA in SFTS patients. The risk score is calculated as 5 times age, plus 6 times neurological complications, plus 10 times RNA (log), plus 5 times WBC, minus 5 times PLT, minus 5 times ALB, plus 5 times GLB, and plus 6 times cTNI. ROC curve analysis showed that the area under the receiver operating characteristic (AUROC) curve represented a risk score of 0.837 (95% CI: 0.789-0.885, p < 0.001) for predicting IPA in SFTS patients. The average length of hospitalization in the SAPA group was more prolonged than non-SAPA. SAPA and non-SAPA groups had significantly different mortality rates: 25.42% (SAPA) and 3.97% (non-SAPA) (p < 0.05). Conclusion: SFTS patients with IPA have high morbidity and mortality. Early monitoring of neurological complications, SFTSV RNA loads, WBC, PLT, ALB, GLB, and cTNI in SFTS patients may be useful in predicting the occurrence of IPA.

Corilagin relieves atherosclerosis via the toll-like receptor 4 signaling pathway in vascular smooth muscle cells.

INTRODUCTION: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis. METHODS: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining. RESULTS: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques. CONCLUSION: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.

Therapeutic potential of natural products in schistosomiasis-associated liver fibrosis.

Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause of hepatosplenomegaly and fibrotic lesions. Anti liver fibrosis therapy is crucial for patients with chronic schistosomiasis. Although Praziquantel is the only clinical drug used, it is limited in insecticide treatment and has a long-term large-scale use, which is forcing the search for cost-effective alternatives. Previous research has demonstrated that plant metabolites and extracts have effective therapeutic effects on liver fibrosis associated with schistosomiasis. This paper summarizes the mechanisms of action of metabolites and some plant extracts in alleviating schistosomiasis-associated liver fibrosis. The analysis was conducted using databases such as PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases. Some plant metabolites and extracts ameliorate liver fibrosis by targeting multiple signaling pathways, including reducing inflammatory infiltration, oxidative stress, inhibiting alternate macrophage activation, suppressing hepatic stellate cell activation, and reducing worm egg load. Natural products improve liver fibrosis associated with schistosomiasis, but further research is needed to elucidate the effectiveness of natural products in treating liver fibrosis caused by schistosomiasis, as there is no reported data from clinical trials in the literature.

Corilagin alleviates atherosclerosis by inhibiting NLRP3 inflammasome activation via the Olfr2 signaling pathway in vitro and in vivo.

Introduction: Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production. Methods: To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE-/- mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein. Results: The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway. Discussion: Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.

Current Status of Malaria Control and Elimination in Africa: Epidemiology, Diagnosis, Treatment, Progress and Challenges.

The African continent carries the greatest malaria burden in the world. Falciparum malaria especially has long been the leading cause of death in Africa. Climate, economic factors, geographical location, human intervention and unstable security are factors influencing malaria transmission. Due to repeated infections and early interventions, the proportion of clinically atypical malaria or asymptomatic plasmodium carriers has increased significantly, which easily lead to misdiagnosis and missed diagnosis. African countries have made certain progress in malaria control and elimination, including rapid diagnosis of malaria, promotion of mosquito nets and insecticides, intermittent prophylactic treatment in high-risk groups, artemisinin based combination therapies, and the development of vaccines. Between 2000 and 2022, there has been a 40% decrease in malaria incidence and a 60% reduction in mortality rate in the WHO African Region. However, many challenges are emerging in the fight against malaria in Africa, such as climate change, poverty, substandard health services and coverage, increased outdoor transmission and the emergence of new vectors, and the growing threat of resistance to antimalarial drugs and insecticides. Joint prevention and treatment, identifying molecular determinants of resistance, new drug development, expanding seasonal malaria chemo-prevention intervention population, and promoting the vaccination of RTS, S/AS01 and R21/Matrix-M may help to solve the dilemma. China's experience in eliminating malaria is conducive to Africa's malaria prevention and control, and China-Africa cooperation needs to be constantly deepened and advanced. Our review aims to help the global public develop a comprehensive understanding of malaria in Africa, thereby contributing to malaria control and elimination.

The History of Controlling and Treating Infectious Diseases in Ancient China.

Infectious diseases are the common enemies of mankind. In the course of historical development, they persistently threaten human health and safety. Even today, despite the developments in medical science, we cannot escape the fear and suffering caused by infectious diseases. Whether in ancient or modern times, the source of infection, route of transmission, and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases. All factors closely related to these three conditions can affect the prevalence of infectious diseases. China is one of the cradles of world civilization. The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases. In the face of the current threat posed by widespread infectious disease, it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease. The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights, especially for impoverished and medically underserved regions.

Agent in Urgent Need of Clinical Practice: Corilagin.

Corilagin is a naturally occurring water-soluble retrogallic acid tannin, which can be extracted from many kinds of plants. Known at present, it is the main effective ingredient of Phyllanthus urinaria L., Geranium wilfordii Maxim., Phyllanthus matsumurae Hayata, and Trifolium repens L. It also exists in Phyllanthus emblica L., Dimocarpus longan Lour., Canarium album (Lour.) Raeusch., and Terminalia chebula Retz. It can participate in a variety of signaling pathways in vivo and has multiple biological activities, including antitumor, anti-microbial, anti-oxidation, anti-inflammation, hepatoprotective, anti-allergy, anti-proliferation and so on. Given the limited efficacy of first-line treatments for many diseases such as oncology, chronic liver disease, and rheumatic immune system diseases, and the potential for adverse effects to outweigh the therapeutic effects, attention is being focused on alternative treatments, and natural plant extracts are a natural target for alternative treatments, as natural substances tend to have low toxicity to normal tissues. Some proprietary Chinese medicines containing corilagin have been used in clinical applications, being clinically applied to treat chronic liver disease, viral hepatitis B, rheumatoid arthritis and other diseases. This paper reviews the extraction, determination, distribution and harvesting, pharmacokinetics, biological activity, safety assessment of corilagin and its application in clinical practice.

LUNG ULTRASOUND DURING COVID-19 PANDEMICS: WHY, HOW AND WHEN?

OBJECTIVE: The aim: To optimize diagnostic of pathological processes in lungs af f ected by COVID-19, dynamic monitoring and clinical decision making using lung ultrasound in limited resources settings. PATIENTS AND METHODS: Materials and methods: Between the onset of pandemics and January 2021, approximately 9000 patients have been treated for conf i rmed COVID-19 in the Olexandrivska Clinical Hospital. Assessment of all hospitalized patients included hematology, chemistries and proinf l ammatory cytokines - IL-6, CRP, procalcitonin, ferritin. Diagnosis was conf i rmed by PCR for SARS-CoV-2 RNA. Chest X-ray was performed in all hospitalized cases, while CT was available approximately in 30% of cases during hospital stay. Lung ultrasound was proactively utilized to assess the type and extent of lung damage and to monitor the progress of disease in patients hospitalized into the ICU and Infection Unit (n=135). Ultrasound fi ndings were recorded numerically based on scales. RESULTS: Results: In the setting of СOVID-19, bedside lung ultrasound has been promptly recognized as a tool to diagnose and monitor the nature and extent of lung injury. Lung ultrasound is a real time assessment, which helps determine the nature of a pathologic process af f ecting lungs. In this paper the accuracy of bedside LUS, chest X-ray and computer tomography are compared based on clinical cases, typical for COVID-19 lung ultrasound appearance is evaluated. Described in article data is collected in one of the biggest facility that deals with COVID-19. Chest X-ray was performed in all hospitalized cases, while CT was available approximately in 30% of cases during hospital stay. The cases presented in the paper indicate potential advantages to the use of ultrasound in limited resource healthcare settings, especially when the risk of transportation to CT outweighs the value of information obtained. CONCLUSION: Conclusions: Grading of ultrasonographic findings in the lungs was suf f i cient for both initial assessment with identif ication of high risk patients, and routine daily monitoring. Hence, lung ultrsound may be used to predict deterioration, stratify risks and make clinical decisions.