Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis

Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.

Glycolytic dysregulation in Alzheimer's disease:unveiling new avenues for understanding pathogenesis and improving therapy

Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.

TCM diagnosis and treatment theory of chronic complete occlusion of coronary artery based on etiology and pathogenesis

Chronic total occlusive disease of the coronary artery belongs to the category of"chest palsy"and"true heart pain"in traditional Chinese medicine.Its etiology has two aspects:deficiency of blood,blood stasis,qi stagnation,and phlegm.Failure can be caused by deficiency or disease.The pathogenesis of this disease is caused by obstruction of the heart pulse,and its pathogenesis can be transformed into each other.The theory of traditional Chinese medicine believes that the general rule is not painful.Therefore,the treatment of coronary CTO lesions should be based on the combination of Tong and Tong tonic.The chronic complete occlusive disease of the coronary artery can be treated through Xuanbi Tongyang,Huoxue Tongluo,and Aroma Wentong.Based on the Chinese medicine's understanding of the etiology and pathogenesis of coronary CTO lesions,it provides a basis for the diagnosis and treatment of traditional Chinese medicine,solves the problems of interventional medicine in western medicine,and gives play to the unique advantages of traditional Chinese medicine for clinical diagnosis and treatment.

Mechanism of sex hormone level in biological clock disorder induced acne and analysis of TCM Pathogenesis

Acne vulgaris is a common chronic inflammatory disease of pilosebaceous units. And sex hormone level disorder has became a hot research topic in the pathogenesis of acne. Studies show that the biological clock disorder can result in the disorder of sex hormone levels which causes or aggravates acne. Biological clock disorder coincides naturally with "sleep rhythm disorder" in Traditional Chinese Medicine(TCM). In this paper, we will discuss the modern medical mechanism of the biological clock disorder resulting in acne from the angle of sex hormones, and analyze the TCM pathogenesis of the disease caused by the disorder of the biological clock.

Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives

Diabetic kidney disease(DKD)is one of the major chronic complications of diabetes mellitus(DM),as well as a main cause of end-stage renal disease.Over the last few years,substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD.Metabolites of gut microbiota like lipopolysaccharide,short-chain fatty acids,and trimethylamine N-oxide are key mediators of microbial–host crosstalk.However,the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown.Besides,strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently,representing a new potential remedial target for DKD.In this minireview,we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.

Interstitial lung disease in rheumatoid arthritis:Current concepts in pathogenesis,diagnosis and therapeutics

Rheumatoid arthritis(RA) is the most common chronic autoimmune inflammatory joint disease. RA-associated interstitial lung disease(RA-ILD) is a major extraarticular complication and causes symptoms that lead to a deterioration in the quality of life, high utilization of health resources, and an increased risk of earlier mortality. Early in the course of RA-ILD, symptoms are highly variable, making the diagnosis difficult. Therefore, a rational diagnostic strategy that combines an adequate clinical assessment with the appropriate use of clinical tests, including pulmonary function tests and high-resolution computed tomography, should be used. In special cases, lung biopsy or bronchioalveolar lavage should be performed to achieve an early diagnosis. Several distinct histopathological subtypes of RA-ILD are currently recognized. These subtypes also have different clinical presentations, which vary in therapeutic response and prognosis. This article reviews current evidence about the epidemiology of RA-ILD and discusses the varying prevalence rates observed in different studies. Additionally, aspects of RA-ILD pathogenesis, including the role of cytokines and other molecules such as autoantibodies, as well as the evidence linking several drugs used to treat RA with lung damage will be discussed. Some aspects of the clinical characteristics of RA-ILD are noted, and diagnostic strategies are reviewed. Finally, this article analyzes current treatments for RA-ILD, including immunosuppressive therapies and biologic agents, as well as other therapeutic modalities. The prognosis of this severe complication of RA is discussed. Additionally, this paper examines updated evidence from studies identifying an association between drugs used for the treatment of RA and the development of ILD.

Emerging perspectives on RNA virus-mediated infections:from pathogenesis to therapeutic interventions

RNA viruses continue to pose significant threats to global public health,necessitating a profound understanding of their pathogenic mechanisms and the development of effective therapeutic interventions.This manuscript provides a comprehensive overview of emerging perspectives on RNA virus-mediated infections,spanning from the intricate intricacies of viral pathogenesis to the forefront of innovative therapeutic strategies.A critical exploration of antiviral drugs sets the stage,highlighting the diverse classes of compounds that target various stages of the viral life cycle,underscoring the ongoing efforts to combat viral infections.Central to this discussion is the exploration of RNA-based therapeutics,with a spotlight on messenger RNA(mRNA)-based approaches that have revolutionized the landscape of antiviral interventions.Furthermore,the manuscript delves into the intricate world of delivery systems,exploring innovative technologies designed to enhance the efficiency and safety of mRNA vaccines.By analyzing the challenges and advancements in delivery mechanisms,this review offers a roadmap for future research and development in this critical area.Beyond conventional infectious diseases,the document explores the expanding applications of mRNA vaccines,including their promising roles in cancer immunotherapy and personalized medicine approaches.This manuscript serves as a valuable resource for researchers,clinicians,and policymakers alike,offering a nuanced perspective on RNA virus pathogenesis and the cutting-edge therapeutic interventions.By synthesizing the latest advancements and challenges,this review contributes significantly to the ongoing discourse in the field,driving the development of novel strategies to combat RNA virus-mediated infections effectively.

Animal models for SARS-CoV-2 and SARS-CoV-1 pathogenesis,transmission and therapeutic evaluation

There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections.The coronavirus family,which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2,crossed the species barrier and infected humans,causing a global outbreak in the 21st century.Because humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials,animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of vaccines.The ideal animal models should reflect the viral replication,clinical signs,and pathological responses observed in humans.Different animal species should be tested to establish an appropriate animal model to study the disease pathology,transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease 2019.In this context,the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.

Unraveling autophagy-related pathogenesis in active ulcerative colitis:A bioinformatics approach

In this editorial,we provide commentary on the study by Gong et al.In this original research article,Gong et al employed a bioinformatics approach to investigate the involvement of autophagy in active ulcerative colitis(UC).Through differential gene expression analysis,they identified 58 differentially expressed autophagy-related genes in UC patients compared to healthy controls.Notably,HSPA5,CASP1,SERPINA1,CX3CL1,and BAG3,were found to be upregulated in active UC patients,suggesting their significance as core autophagyrelated targets.Enrichment analysis unveiled associations with crucial signaling pathways and diseases such as middle cerebral artery occlusion and glomerulonephritis.Moreover,immune cell infiltration analysis revealed notable differences in immune cell composition between UC patients and healthy controls.These findings offer valuable insights into the role of autophagy in UC pathogenesis and potential therapeutic targets.

Mitochondrial energy metabolism in diabetic cardiomyopathy:Physiological adaption,pathogenesis,and therapeutic targets

Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes,which could eventually develop heart failure and leads to the death of the patients.Although blood glucose control and medications to heart failure show beneficial effects on this disease,there is currently no specific treatment for diabetic cardiomyopathy.Over the past few decades,the pathophysiology of diabetic cardiomyopathy has been extensively studied,and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target.In this review,we summarize the latest research in the field of diabetic cardiomyopathy,focusing on mitochondrial damage and adaptation,altered energy substrates,and potential therapeutic targets.A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.

The roles and mechanisms of miRNA in HBV-HCC carcinogenesis:Why no therapeutic agents after 30 years?

Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only a small subset of late-stage HCC patients responds positively to recently developed therapeutic innovations.MicroRNAs (miRNAs) act as an ancillary epigenetic system that can regulate genome expression in all cancerpathways including HCC. The molecular mechanisms of miRNA regulation in cancer pathogenesis offered researchersa new approach that was widely hoped would translate into miRNA-based drugs and diagnostics. Thirty years on,miRNA-based diagnostic and therapeutic agents for HCC remain a work-in-progress (WIP) and no current miRNAHCC clinical trial has progressed to Phase 4. The question remains why this is the case after 30 years and what is theway forward. The major findings and contribution of this paper are that it illustrates the complexity of the HBVmiRNA interactome in HBV-HCC in all cellular processes, as well as the ancillary role of miRNA in the epigeneticand immune systems. This is combined with a review of the outcomes and problems of clinical trials, to explain whymiRNA therapeutics and diagnostics have not progressed to approved drugs or serum-based diagnostic tests. The wayforward suggests a radical rethink might be so that involves the incorporation of AI, bioinformatics, andnanotechnology to solve the problem.

Zhang Xijian, a famous Chinese medicine practitioner in China, discusses the pathogenesis characteristics of adolescent central obesity based on "qi change theory"

Obesity[1]is a group of common and ancient metabolic diseases.Central obesity is common in clinical practice.Due to the simple constitution of adolescents,their pathogenesis is simple and changeable,or there is a mixture of cold and heat,or a mixture of cold and heat,or the same disease on the surface,and the pathogenesis of traditional Chinese medicine is complex and changeable.The pathogenesis of TCM pathogenesis of adolescent central obesity is analyzed with examples to provide new theoretical ideas for the treatment of obesity by Chinese medicine.

MicroRNAs in idiopathic pulmonary fibrosis: involvement in pathogenesis and potential use in diagnosis and therapeutics

MicroRNAs (miRNAs) are a class of phylogenetically conserved, non-coding short RNAs, 19-22 nt in length which suppress protein expression through base-pairing with the 3'-untranslated region of target mRNAs. miRNAs have been found to participate in cell proliferation, differentiation and apoptosis. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high lethality fibrotic lung disease for which currently there is no effective treatment. Some miRNAs have been reported to be involved in the pathogenesis of pulmonary fibrosis. In this review, we discuss the role of miRNAs in the pathogenesis, diagnosis and treatment of IPF. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND

Advances in COVID-19:the virus,the pathogenesis,and evidence-based control and therapeutic strategies

Since the outbreak of the COVID-19 pandemic in early December 2019,81174 confirmed cases and 3242 deaths have been reported in China as of March 19,2020.The Chinese people and government have contributed huge efforts to combat this disease,resulting in significant improvement of the situation,with 58 new cases(34 were imported cases)and 11 new deaths reported on March 19,2020.However,as of March 19,2020,the COVID-19 pandemic continues to develop in 167 countries/territories outside of China,and 128665 confirmed cases and 5536 deaths have been reported,with 16498 new cases and 817 new deaths occurring in last 24 hours.Therefore,the world should work together to fight against this pandemic.Here,we review the recent advances in COVID-19,including the insights in the virus,the responses of the host cells,the cytokine release syndrome,and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm.By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis,we believe that the community can efficiently develop effective vaccines and drugs,and the mankind will eventually win this battle against this pandemic.

Rules and Characteristics of TCM Treatment Prescriptions for Patients with Decreased Ovarian Reserve

[Objectives]To analyze the characteristics and rules of traditional Chinese medicine(TCM)in the treatment of decreased ovarian reserve(DOR)in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine.[Methods]A total of 107 patients with DOR in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine were selected for sorting,and the usage,classification,nature,taste and meridian homing of the used drugs were statistically analyzed.[Results]A total of 107 patients were included in this stud and a total of 189 flavors of TCM are used.The total frequency of drugs was 4345 times,and a total of 535 prescriptions were issued.The top five frequency of drug use were 2261 times(50.04%)of Paeoniae Radix Alba(Cynanchum otophyllum Schneid.),2037 times(46.88%)of Corni Fructus(Cornus officinalis Sieb.et Zucc.),1818 times(41.84%)of Rehmanniae Radix Praeparata[Rehmannia glutinosa(Gaertn.)Libosch EX Fisch.et Mey.],1610 times(37.05%)of Guiban[Chinemys reevesii(Gray)],and 1303 times(29.99%)of Uncariae Ramulus Cum Uncis(Uncariar hynchophylla Miq.ex Havil.).Kidney deficiency syndrome accounted for the largest proportion at 51.40%,and the use frequency of tonic drugs accounted for the highest at 50.64%;heat-clearing drugs and qi and blood-boosting drugs separately accounted for 19.24%and 17.39%;the top 3 medicinal tastes are sweet(52.02%),pungent(20.71%)and bitter(20.32%);medicinal properties are ranked as warm(60.54%),cold(24.16%),hot(8.72%)and cool(6.49%);the main meridians are spleen,lung,liver,stomach and kidney.[Conclusions]The basic pathogenesis of DOR is deficiency of qi and blood,mainly due to dysfunction of the spleen,lung,liver,liver,stomach and other organs,and kidney deficiency and spleen deficiency are more common.

Cellular and molecular mechanisms implicated in pathogenesis of selective neurodegeneration in Huntington＇s disease

Huntington＇s disease （HD） is one of the most common dominantly-inherited neurodegenerative disorders and is caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by selective degeneration of subpopulations of neurons in the brain, however the precise underlying mechanisms how a ubiquitously expressed disease protein could target specific types of neurons for degeneration remains a critical, yet unanswered question for HD and other major neurodegenerative disorders. In this review, we describe the expanding view of selective neuronal vulnerability in HD, based on recent neuropathological and neuroimaging studies. We will also summarize the systematic effort to define the cell types in which mutant Huntingtin expression is critical for pathogenesis of vulnerable neurons in the striatum and cortex. Finally, we will describe selected, emerging molecular mechanisms that are implicated in selective disease processes in HD. Together, the field has begun to appreciate the distinct molecular pathogenic roles of mutant huntingtin in different cell types that may contribute to the selective neuronal vulnerability, with dissection of such mechanisms likely to yield novel molecular targets for HD therapy.

Brief introduction to the historical development and therapeutic effects of cupping therapy in traditional Chinese medicine

Cupping therapy (CT) is an ancient traditional and complementary medicine practice. Recently, there has been a growing evidence of its potential benefits in the treatment of various diseases. The CT has been constantly developing with the emergence of various modern and improved cupping devices. It is now evident that cupping could adjust the Qi, blood, Yin and Yang, dredge the meridian, as well as relieve the effect of illness, achieve fitness and relative equilibrium of Yin-Yang. It exerts its effects through the negative pressure suction via the mechanical and thermal stimulations, and the negative pressure effects induced by cupping. This article gives an overview of CT practice, its historical development, as well as its therapeutic effects and mechanism. Furthermore, a new and updated classification of CT was briefly introduced.

The progress and related pharmacological mechanism of hyperlipidemia treatment

Hyperlipidemia(HLP)is a long-known risk factor for a series of cardiovascular and cerebrovascular diseases,such as atherosclerosis,coronary heart disease,hypertension and so on.With its increasing incidence,the prevention and treatment of HLP has also become an important research topic around the world.Traditional Chinese medicine(TCM)has been used to treat HLP for a long time with its better therapeutic efficacy,less side effects and wider indications compared with western medicine.In this review,we summarized the pathogenesis of HLP,the research situation of disease-related targets,and the treatment progress of TCM by conducting literature research and sorting out relevant information,in order to provide reference for further research of HLP and prevent the occurrence of cardiovascular and cerebrovascular diseases.

Prevention and Treatment of “Epidemic Toxin, Pathogenic Dampness, and Lung Deficiency” after COVID-19 Recovery Based on the Theory of “Preventive Treatment of Diseases” in Traditional Chinese Medicine

Due to the sequelae and recurrence in patients with COVID-19 after recovery.This article,based on lire theory of“preventive treatment of diseases”in traditional Chinese medicine,winch believes that the three pathogenic factors of epidemic toxin,dampness,and lung deficiency are the fundamental causes of the recurrence of COVID-19.The treatment strategies are to remove pathogenic factors,strengthen qi,nourish yin,clear heat,moisten dryness,and at the same time,reinforce the lung,spleen and kidney,and soothe the liver.Through a variety of treatments such as oral administration,external treatment,and skin absorption,it provides a new idea and method for the management of the recurrence of COVID-19.

Prevention and Treatment of“Epidemic Toxin,Pathogenic Dampness,and Lung Deficiency”after COVID‑19 Recovery Based on the Theory of“Preventive Treatment of Diseases”in Traditional Chinese Medicine

Due to the sequelae and recurrence in patients with COVID-19 after recovery.This article,based on the theory of“preventive treatment of diseases”in traditional Chinese medicine,which believes that the three pathogenic factors of epidemic toxin,dampness,and lung deficiency are the fundamental causes of the recurrence of COVID‑19.The treatment strategies are to remove pathogenic factors,strengthen qi,nourish yin,clear heat,moisten dryness,and at the same time,reinforce the lung,spleen and kidney,and soothe the liver.Through a variety of treatments such as oral administration,external treatment,and skin absorption,it provides a new idea and method for the management of the recurrence of COVID‑19.