Pulmonary hypertension （PH） is a life-threatening condition characterized by a progressive elevation in pulmonary vascular pressure， ultimately leading to right ventricular dysfunction and failure. The core pathological features of PH include abnormal contraction of small pulmonary arteries and vascular remodeling. In recent years， endoplasmic reticulum stress （ERS）， a critical adaptive response of cells to internal and external stressors， has been shown to play a key role in the development and progression of PH. Through the activation of major signaling pathways such as protein kinase R-like endoplasmic reticulum kinase （PERK）， inositol-requiring enzyme 1α （IRE1α）， and activating transcription factor 6 （ATF6）， ERS is directly involved in regulating aberrant cellular behaviors and vascular remodeling in PH. This review systematically discusses the specific role of ERS in the pathogenesis of PH and evaluates its potential as a therapeutic target， aiming to provide a theoretical foundation for novel clinical interventions in PH.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with diverse phenotypes and endotypes. The emphysema phenotype, characterized by destruction of the terminal bronchioles and alveolar walls, is associated with more severe lung function impairment, heightened airway inflammation, and greater systemic dysfunction compared to other subtypes. Early diagnosis via biomarkers, signaling pathway analysis, and imaging, combined with targeted therapies, may improve patient outcomes. However, further research is needed to fully elucidate this phenotype. This review summarizes recent advances in the pathology, biomarkers, signaling pathways, and clinical management of the emphysema phenotype of COPD, aiming to enhance its recognition and inform future research.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with diverse phenotypes and endotypes. The emphysema phenotype, characterized by destruction of the terminal bronchioles and alveolar walls, is associated with more severe lung function impairment, heightened airway inflammation, and greater systemic dysfunction compared to other subtypes. Early diagnosis via biomarkers, signaling pathway analysis, and imaging, combined with targeted therapies, may improve patient outcomes. However, further research is needed to fully elucidate this phenotype. This review summarizes recent advances in the pathology, biomarkers, signaling pathways, and clinical management of the emphysema phenotype of COPD, aiming to enhance its recognition and inform future research.

Chronic obstructive pulmonary disease (COPD) is a chronic, heterogeneous inflammatory disease with high prevalence and mortality rate. Although current treatments can relieve symptoms, they cannot prevent further decline in lung function. With the development of stem cell therapy, mesenchymal stem cells and their extracellular vesicles have received widespread attention for their anti-inflammatory, immune regulation, tissue regeneration and repair functions, aging, and other applications in the treatment of lung diseases. This article reviews the role and clinical application prospects of mesenchymal stem cells and their derived exosomes in chronic obstructive pulmonary disease and its complications.

Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic respiratory condition, often accompanied by various comorbidities. Sarcopenia is a significant comorbidity of COPD, impacting its progression and prognosis, therefore early intervention is crucial. Intervention for COPD with sarcopenia includes non-pharmacological and pharmacological measures. Non-pharmacological intervention encompass respiratory rehabilitation, nutritional interventions and exercise training; while pharmaceutical intervention is still in its nascent stages. This article presents a comprehensive review of the research progress on intervention measures for COPD with sarcopenia, aiming to provide insights for prevention and management of this condition.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly virulent variant of Klebsiella pneumoniae and can cause systemic invasive infection. The worldwide prevalence of hvKP infection continues to increase. Diabetic patients, especially those with poor glucose control, are at a higher risk for hvKP infection. The infection of hvKP in diabetic patients is characterized by high incidence, rapid progression and high fatality rate. The mechanisms underlying the susceptibility to hvKP in patients with diabetes include hyperglycemia-induced bacterial translocation, endothelial-epithelial barrier damage, immune evasion, high-load bacteremia, microthrombosis and hvKP carbon/iron metabolism-based regulation of virulence. A thorough understanding of the mechanisms underlying the susceptibility to hvKP in diabetic patients will be great significant to further improve clinical understanding and attention, and provide early prevention and effective diagnosis and treatment. This article summarizes the progress in the mechanisms of susceptibility to hvKP in diabetic patients in recent years.

Background::Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US.Methods::The deaths, and mortality rates of asthma in China and the US during 1990–2019 were obtained from the Global Burden of Disease Study 2019. The age–period–cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated.Results::In 1990–2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively.Conclusions::In 1990–2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

Purpose: Explore the causal relationship between the gut microbiota and erectile dysfunction (ED) at phylum, class, order, family, and genus levels, and identify specific pathogenic bacteria that may be associated with the onset and progression of ED. Materials and Methods: The genetic variation data of 196 human gut microbiota incorporated in our study came from the human gut microbiome Genome Wide Association Studies (GWAS) dataset released by the MiBioGen Consortium. The GWAS statistics for ED were extracted from one study by Bovijn et al., which included 223,805 participants of European ancestry, of whom 6,175 were diagnosed with ED. Subsequently, Mendelian randomization (MR) analysis was carried out to explore whether a causal relationship exists between the gut microbiota and ED. Additionally, bidirectional MR analysis was performed to examine the directionality of the causal relationship. Results: Through MR analysis, we found that family Lachnospiraceae (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.05–1.52, p=0.01) and its subclass genus LachnospiraceaeNC2004 group (OR: 1.17, 95% CI: 1.01–1.37, p=0.04) are associated with a higher risk of ED. In addition, genus Oscillibacter (OR: 1.17, 95% CI: 1.02–1.35, p=0.03), genus Senegalimassilia (OR: 1.32, 95% CI: 1.06–1.64, p=0.01) and genus Tyzzerella3 (OR: 1.14, 95% CI: 1.02–1.27, p=0.02) also increase the risk of ED. In contrast, the inverse variance weighted estimate of genus RuminococcaceaeUCG013 (OR: 0.77, 95% CI: 0.61–0.96, p=0.02) suggests that it has a protective effect against the occurrence of ED. Conclusions This study preliminarily identified 6 bacterial taxa that may have a causal relationship with ED, including family Lachnospiraceae, genus Lachnospiraceae NC2004 group, Oscillibacter, Senegalimassilia, Tyzzerella 3 and Ruminococcaceae UCG013. These identified important bacterial taxa may serve as candidates for microbiome intervention in future ED clinical trials.

ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man （OMIM）. The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects， and protein-protein interaction （PPI） network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1， PyMol， and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets. ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out， and the core targets with high activities were protein kinase B1 （Akt1）， interleukin-1β （IL-1β）， cellular tumor antigen p53 （TP53）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and matrix metalloproteinase-9 （MMP-9）. According to the structures， the flavonoids in Cyperi Rhizoma were classified into bioflavonoids， flavonols， flavones， and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets， while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53， while the change of B ring substituents was not the main factor affecting the binding affinity. The 3，4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53， while the two compounds showed similar binding affinity to PTGS2. ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo reveal the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma by structure-activity omics. MethodOn the basis of the previous study about the screening of active components in vitro， this study explored the effects of flavonoids in Glycyrrhizae Radix et Rhizoma in vivo. The flavonoids in Glycyrrhizae Radix et Rhizoma and their direct targets for the anti-inflammatory and analgesic effects were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， DisGeNET， and Online Mendelian Inheritance in Man （OMIM）. STRING and Cytoscape 3.7.2 were employed to establish the protein-protein interaction （PPI） network of key targets. Molecular docking was performed to simulate the binding of five targets with high degrees to flavonoids in Glycyrrhizae Radix et Rhizoma， on the basis of which the key core targets were selected. The targets were used as a bridge to correlate the structures and effects of one or more classes of chemical components in Glycyrrhizae Radix et Rhizoma. According to the binding affinity between flavonoids with different structures in Glycyrrhizae Radix et Rhizoma and targets， the relationships between compound structures and core targets were discussed. ResultThe flavonoids in Glycyrrhizae Radix et Rhizoma reduced the content of prostaglandin E₂ （PGE₂） in the rat model of pain induced by formalin， demonstrating definite anti-inflammatory and analgesic effects. Sixty active compounds （flavonoids） with anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma were obtained. With the total score as the standard， prostaglandin-endoperoxide synthase 2 （PTGS2） and mitogen-activated protein kinase 3 （MAPK3） were selected as the key core targets of Glycyrrhizae Radix et Rhizoma for the anti-inflammatory and analgesic effects. Except that flavones showed selectivity of binding to MAPK3， the other flavonoids of Glycyrrhizae Radix et Rhizoma showed strong binding to PTGS2 and MAPK3， and the structures containing glycoside fragments showed stronger binding affinity to the targets. The introduction of chain olefins in the ring of chalcones facilitated the binding to the targets. The isopentenyl fragment in flavonols may cause the difference in binding affinity. The parallel combination of a ring into pyran ring in flavanes was not conducive to the binding to the target. The electric charge， liposolubility， and steric hindrance of the substituent group on the B ring of isoflavones directly affected the binding affinity. ConclusionThis study adopts structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma. Structure-activity omics provides new ideas and methods for predicting the pharmacodynamic substances of traditional Chinese medicine.