Tibetan mesenchymal stem cell-derived exosomes alleviate pulmonary vascular remodeling in hypoxic pulmonary hypertension rats.

Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-ß1/Smad2/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGFß pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGFß1 and p-Smad2/3. Furthermore, TGFß1 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGFß1/Smad2/3 pathway via Nbl1.

Human Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Alleviate Hypoxia-Induced Pulmonary Arterial Hypertension in Mice Via Macrophages.

Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH.

Forensic Identification and Evaluation of 25 Obstetric Brachial Plexus Palsy Medical Damage Cases.

OBJECTIVES: To analyze the high risk factors of obstetric brachial plexus palsy (OBPP), and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification. METHODS: A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center. The shortcomings of hospitals in birth weight assessment, delivery mode selection, labor process observation and shoulder dystocia management, and the causal relationship between them and the damage consequences of the children were summarized. RESULTS: Fault medical behavior was assessed as the primary cause in 2 cases, equal cause in 10 cases, secondary cause in 8 cases, minor cause in 1 case, no causal relationship in 1 case, and unclear causal force in 3 cases. CONCLUSIONS: In the process of forensic identification of OBPP, whether medical behaviors fulfill diagnosis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation, delivery mode notification, standardized use of oxytocin, standard operation of shoulder dystocia, etc. Meanwhile, it is necessary to fully consider the objective risk of different risk factors and the difficulty of injury prevention, and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

DDB2 and MDM2 genes are promising markers for radiation diagnosis and estimation of radiation dose independent of trauma and burns.

In the field of biodosimetry, the current accepted method for evaluating radiation dose fails to meet the need of rapid, large-scale screening, and most RNA marker-related studies of biodosimetry are concentrating on a single type of ray, while some other potential factors, such as trauma and burns, have not been covered. Microarray datasets that contain the data of human peripheral blood samples exposed to X-ray, neutron, and γ-ray radiation were obtained from the GEO database. Totally, 33 multi-type ray co-induced genes were obtained at first from the differentially expressed genes (DEGs) and key genes identified by weighted gene co-expression network analysis (WGCNA), and these genes were mainly enriched in DNA damage, cellular apoptosis, and p53 signaling pathway. Following transcriptome sequencing of blood samples from 11 healthy volunteers, 13 patients with severe burns, and 37 patients with severe trauma, 6635 trauma-related DEGs and 7703 burn-related DEGs were obtained. Through the exclusion method, a total of 12 radiation-specific genes independent of trauma and burns were identified. ROC curve analysis revealed that the DDB2 gene performed the best in diagnosis of all three types of ray radiation, while correlation analysis showed that the MDM2 gene was the best in assessment of radiation dose. The results of multiple-linear regression analysis indicated that such analysis could improve the accuracy in assessment of radiation dose. Moreover, the DDB2 and MDM2 genes remained effective in radiation diagnosis and assessment of radiation dose in an external dataset. In general, the study brings new insights into radiation biodosimetry.

Individual factors in dignified care: A cross-sectional study of critical care nurses.

AIM: To determine the level of dignified care provided by critical care nurses, and explore the associated individual factors. BACKGROUND: Dignity is a fundamental right of human beings. Critically ill patients are dependent on nurses. Their need for respect and dignity is liable to be neglected in intensive care unit settings. Both critically ill survivors and dying patients suffer mental anguish due to loss of dignity. METHOD: This was a cross-sectional study of 526 critical care nurses working at intensive care units for adults in Zhejiang Province, China. Data were collected from February 2021 to May 2021 using the Intensive Care Unit Dignified Care Questionnaire, Wong and Law Emotional Intelligence Scale, Jefferson Scale of Empathy-Health Professional and Nurses Professional Values Scale-Revised. RESULTS: The total score of dignified care was 67.37 (8.83), with the standard score as 74.07 (12.99). Participants who performed poorly in absolute and relative dignity accounted for 8.4% and 31.2% of the total sample, respectively. Emotional intelligence (ß = .379, p < .001), empathy (ß = .319, p < .001), professional values (ß = .147, p < .001), age (ß = .075, p = .003) and training in dignified care (ß = .074, p = .010) were associated with dignified care, explaining 67.6% of the variance. CONCLUSION: The average level of participants' behaviours of maintaining patient dignity was medium. Critical care nurses need to improve their ability to maintain relative dignity of patients. Emotional intelligence, empathy, professional values, age level and training in dignified care were predictors of dignified care. IMPLICATIONS FOR NURSING MANAGEMENT: Improving emotional intelligence, empathy and professional values of critical care nurses and training them (especially less experienced nurses) will enhance their ability in dignified care. This study provides a novel perspective to help nursing managers develop interventions to promote humanized care in the intensive care unit.

[Salidroside inhibits phenotypic transformation of rat pulmonary artery smooth muscle cells induced by hypoxia].

This study investigated the effect of salidroside on phenotypic transformation of rat pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia. Rat pulmonary arteries were isolated by tissue digestion and PASMCs were cultured. The OD values of cells treated with salidroside at different concentrations for 48 hours were measured by cell counting kit-8(CCK-8) to determine the appropriate concentration range of salidroside. The cells were divided into a normal(normoxia) group, a model(hypoxia) group, and three hypoxia + salidroside groups(40, 60, and 80 µg·mL~(-1)). Quantitative real-time PCR(qRT-PCR) was used to detect the mRNA expression of cell contractile markers in each group, such as α-smooth muscle actin(α-SMA), smooth muscle 22(SM22), and calcium-binding protein(calponin), and synthetic marker vimentin. The expression levels of cell phenotypic markers and proliferating cell nuclear antigen(PCNA) were detected by Western blot. The proliferation of cells in each group was detected by the 5-ethynyl-2'-deoxyuridine(EdU) assay. Cell migration was measured by Transwell assay. As revealed by results, compared with the normal group, the model group showed decreased mRNA and protein expression of contractile phenotypic markers of PASMCs and increased mRNA and protein expression of synthetic markers. Compared with the conditions in the model group, salidroside could down-regulate the mRNA and protein expression of synthetic markers in PASMCs and up-regulated the mRNA and protein expression of contractile phenotypic markers. Compared with the normal group, the model group showed potentiated proliferation and migration. Compared with the model group, the hypoxia + salidroside groups showed blunted proliferation and migration of cells after phenotypic transformation. The results suggest that salidroside can inhibit the expression of synthetic markers in PASMCs and promote the expression of contractile markers to inhibit the hypoxia-induced phenotypic transformation of PASMCs. The mechanism of salidroside in inhibiting the proliferation and migration of PASMCs is related to the inhibition of the phenotypic transformation of PASMCs.

A Case of Human Hepatic Alveolar Echinococcosis Accompanied by Lung and Brain Metastases.

Alveolar echinococcosis (AE) is considered as a fatal zoonosis caused by the larvae of Echinococcus multilocularis. The lungs and brain are the most common metastatic organs. We report a human case of hepatic alveolar echinococcosis accompanied by lung and brain metastasis. In particular, the patient had a history of tuberculosis and the lung lesions were easily misdiagnosed as lung abscesses. The lesions of liver and lung underwent radical resection and confirmed as alveolar echinococcosis by pathological examination. The patient had no surgical complications after operation and was discharged after symptomatic treatment. Unfortunately, the patient later developed multiple intracerebral AE metastases. We required the patient to take albendazole orally for life and follow up.

Decreased Colorectal Adenoma Risk After Helicobacter pylori Eradication: A Retrospective Cohort Study.

BACKGROUND: Helicobacter pylori infection is associated with colorectal adenoma and confers a 1.3- to 2.26-fold increased risk. We evaluated the association between H. pylori and the progression of colorectal adenoma. METHODS: This retrospective cohort study included 615 adults with no history of colorectal adenoma or cancer at baseline who participated in a repeated, regular health screening examination, which included a bidirectional gastrointestinal endoscopy, between July 2006 and June 2015. A gastric biopsy specimen from each subject was tested for H. pylori. RESULTS: During follow-up, the incidence rates of colorectal adenoma progression in participants with persistent H. pylori infections (persistent group) and those whose infections had previously been successfully eradicated (eradication group) were 160.52 and 51.60 per 1000 person-years, respectively (P = .0003). After adjustment for confounding factors, the persistent group exhibited a higher risk of colorectal adenoma than the eradication group (hazard ratio = 3.04, 95% CI 1.899, 5.864). The colorectal adenoma ratio of patients uninfected with H. pylori was similar to that of the eradication group (23.93% vs 20.12%, P = .328). CONCLUSIONS: Persistent H. pylori infection was associated significantly with the independent development of colorectal adenoma. H. pylori infection may have a pathophysiological role in colorectal adenoma development and, after successful eradication of H. pylori, the colorectal adenoma ratio might decrease.

[Regional homogeneity changes in patients with obstructive sleep apnea-hypopnea syndrome: resting-state functional MRI study].

OBJECTIVE: To investigate the change of regional homogeneity (ReHo) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) using resting-state functional magnetic resonance imaging(fMRI). METHODS: Resting-state fMRI data were collected from 15 patients with OSAHS and 15 normal controls. Patients were enrolled from the Sleep Laboratory of the Otolaryngology-Head and Neck Surgery Department of Zhongda Hospital, Southeast University, Nanjing from November 2014 to June 2015. The data were analyzed with the ReHo method and compared between OSAHS and controls. RESULTS: The ReHo showed a significant increase in the posterior lobe of right cerebellum (t=4.292 1, P<0.01), posterior lobe of left cerebellum (t=4.350 6, P<0.01), right brainstem (t=5.276 6, P<0.01), right occipital lobe (t=3.620 9, P= 0.001), left basal ganglia (t=3.385 6, P=0.002) and left temporal lobe (t=4.781 2, P<0.01) and a decrease in the right middle frontal gyrus (t=-3.564 4, P= 0.001), right inferior parietal lobe (t=-4.123 7, P<0.01) and bilateral superior frontal gyrus (t=-3.500 9, P=0.002) in patients with OSAHS. Furthermore, the average ReHo values of the posterior lobe of bilateral cerebellum was positively correlated with the MMSE scores (r=0.682, P=0.012), the LMT scores (r=0.623, P=0.013) and the LMT-delayed recall scores (r=0.577, P=0.024), while negatively correlated with the TMT-A scores (r=-0.723, P=0.002); the average ReHo values of the right middle frontal gyrus (r=0.661, P=0.007) was positively correlated with the TMT-A scores. CONCLUSION: The current findings indicate that significant changes of ReHo in the global brain regions have been detected in OSAHS patients and the compensatory change of brain function occur. Abnormal ReHo values in the posterior lobe of bilateral cerebellum and right middle frontal gyrus could serve as potential biomarkers for assessment of neuronal damage and further provides insights into the biological mechanism of the disease.

Effects of health intervention program on cardiometabolic risk profiles from health evaluation center in Asian population: a longitudinal study and propensity analysis.

BACKGROUND: Health intervention program (HIP) based on diet and lifestyle modifications had been shown to improve cardiovascular risks. The effects of such program on a variety of cardiometabolic outcome measures conducted in a strict analysis remained relatively unexplored. MATERIALS AND METHODS: A total of 2,660 participants (mean age: 43.3 ± 10 years, 63.6% male) underwent annual health survey from our health evaluation department. We implemented health intervention program (HIP) in which diet and lifestyle modifications including smoking cessation and advised physical activities were introduced. We further studied the effects of HIP on several cardiometabolic outcome measures including Framingham, metabolic scores and renal function in terms of Egfr with a mean follow-up period of 38.5 months. Propensity score (PS) matching (HIP vs non-HIP group) was used to avoid effects of case selection bias. RESULTS: Totally 1,004 (502 subjects for each group) left after PS matching protocol (both HIP and non-HIP group). The HIP group showed significant decline of waist circumference (-1.46 ± 0.61, p = 0.016), post-prandial glucose (-6.77 ± 2.06, p = 0.001), and total cholesterol level (-4.42 ± 2.15, p = 0.04), with borderline increase in eGFR (1.72 ± 0.94, p = 0.068) after an average of 1.91 ± 1.14 year follow up period. Exercise behavior significantly increased for those who received HIP when compared to the non-HIP group (44.6 vs 52.4 %, p = 0.014). PS matching and difference-in-difference (DID) analysis further confirmed the beneficial effects of ATP III reduction by HIP (-0.36 ± 0.06, p < 0.05). CONCLUSION: We demonstrated in our study that several cardiometabolic profiles can be substantially improved after health intervention introduction at the health evaluation center, supporting the beneficial evidence of such health intervention programs implementation based on primary prevention view points.

Epididymal alveolar echinococcosis and tuberculosis co-infection: A case report.

Alveolar echinococcosis (AE) is a common and significant public health problem caused by the larvae of the Echinococcus multilocularis. The occurrence of epididymal AE is rare and often overlooked in combination with mycobacterium tuberculosis infection. We report a case of a 34-year-old man who presented with right-sided scrotal enlargement with pain. Physical examination revealed an enlarged right scrotum with rupture. CT examination showed a blurred border and non-enhancing lesion on the right epididymis. Postoperative pathology and molecular biology identified an epididymal E. multilocularis infection. We report this rare case to emphasise the difficulty of preoperative diagnosis and the importance of complete surgical excision of the lesion.

A case report of human primary renal cystic echinococcosis.

In humans, solitary renal involvement or primary renal echinococcosis is rare, accounting for about 2-4 % of cases. Usually, patients shpw no obvious symptoms, but they can manifest as renal pain, renal mass, gross hematuria, and hydatiduria in rare cases. We report a case of primary renal cystic echinococcosis, which was originally misdiagnosed as a tuberculous renal abscess.

Efficacy and Safety of Asparagusic Acid against Echinococcus multilocularis In Vitro and in a Murine Infection Model.

Alveolar echinococcosis (AE) stands as a perilous zoonotic affliction caused by the larvae of Echinococcus multilocularis. There is an imperative need to explore novel therapeutic agents or lead compounds for the treatment of AE. Asparagusic acid, characterized by its low toxicity and possessing antimicrobial, antioxidant, and anti-parasitic attributes, emerges as a promising candidate. The aim of this study was to investigate the in vivo and in vitro efficacy of asparagusic acid against E. multilocularis. Morphological observations, scanning electron microscopy, ROS assays, mitochondrial membrane potential assays, and Western blot were used to evaluate the in vitro effects of asparagusic acid on protoscoleces. The effects of asparagusic acid on vesicles were assessed via PGI release, γ-GGT release, and transmission electron microscopy observations. CellTiter-Glo assays, Caspase3 activity assays, flow cytometry, and Western blot were used for an evaluation of the effect of asparaginic acid on the proliferation and apoptosis of germinal cells. The in vivo efficacy of asparagusic acid was evaluated in a murine AE model. Asparagusic acid exhibited a pronounced killing effect on the protoscoleces post-treatment. Following an intervention with asparagusic acid, there was an increase in ROS levels and a decline in mitochondrial membrane potential in the protoscolex. Moreover, asparagusic acid treatment resulted in the upregulation of PGI and γ-GGT release in metacestode vesicles, concomitant with the inhibition of germinal cell viability. Furthermore, asparagusic acid led to an enhanced relative expression of Caspase3 in the culture supernatant of both the protoscoleces and germinal cells, accompanied by an increase in the proportion of apoptotic germinal cells. Notably, asparagusic acid induced an augmentation in Bax and Caspase3 protein expression while reducing Bcl2 protein expression in both the protoscoleces and germinal cells. In vitro cytotoxicity assessments demonstrated the low toxicity of asparagusic acid towards normal human hepatocytes and HFF cells. Additionally, in vivo experiments revealed that asparagusic acid administration at doses of 10 mg/kg and 40 mg/kg significantly reduced metacestode wet weight. A histopathological analysis displayed the disruption of the germinal layer structure within lesions post-asparagusic acid treatment, alongside the preservation of laminated layer structures. Transmission electron microscopy further revealed mitochondrial swelling and heightened cell necrosis subsequent to the asparagusic acid treatment. Furthermore, asparagusic acid promoted Caspase3 and Bax protein expression while decreasing Bcl2 protein expression in perilesional tissues. Subsequently, it inhibited the expression of Ki67, MMP2, and MMP9 proteins in the perilesional tissues and curbed the activation of the PI3K/Akt signaling pathway within the lesion-host microenvironmental tissues. Asparagusic acid demonstrated a pronounced killing effect on E. multilocularis, suggesting its potential as a promising therapeutic agent for the management of AE.

Terpolymerization of Ethylene with Hexene and Styrene Derivatives by Half-Sandwich Scandium Catalyst.

The terpolymerization of ethylene with hexene and styrene derivatives was achieved with a rare earth metal catalyst (C5Me4SiMe3)Sc(CH2C6H4NMe2-o)2 to prepare functional polyethylene. The catalyst system exhibited high activity in the terpolymerization of ethylene with hexene and amine-substituted styrene, affording terpolymers a moderate molecular weight and a unimodal molecular weight distribution. In addition, the comonomer content of the terpolymers can be controlled by changing the feeding ratio of monomers. The aliphatic region of the 13C NMR spectra reveals that the structural units of the comonomers are separately incorporated into the polyethylene backbone. Terpolymers containing styrene derivatives exhibit enhanced tensile strength and significantly improve hydrophilic properties.

Nanocarrier-mediated siRNA delivery: a new approach for the treatment of traumatic brain injury-related Alzheimer's disease.

Traumatic brain injury and Alzheimer's disease share pathological similarities, including neuronal loss, amyloid-ß deposition, tau hyperphosphorylation, blood-brain barrier dysfunction, neuroinflammation, and cognitive deficits. Furthermore, traumatic brain injury can exacerbate Alzheimer's disease-like pathologies, potentially leading to the development of Alzheimer's disease. Nanocarriers offer a potential solution by facilitating the delivery of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease. Unlike traditional approaches to neuroregeneration, this is a molecular-targeted strategy, thus avoiding non-specific drug actions. This review focuses on the use of nanocarrier systems for the efficient and precise delivery of siRNAs, discussing the advantages, challenges, and future directions. In principle, siRNAs have the potential to target all genes and non-targetable proteins, holding significant promise for treating various diseases. Among the various therapeutic approaches currently available for neurological diseases, siRNA gene silencing can precisely "turn off" the expression of any gene at the genetic level, thus radically inhibiting disease progression; however, a significant challenge lies in delivering siRNAs across the blood-brain barrier. Nanoparticles have received increasing attention as an innovative drug delivery tool for the treatment of brain diseases. They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier, targeted drug delivery, enhanced drug stability, and multifunctional therapy. The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach. Although this strategy is still in the preclinical exploration stage, it is expected to achieve clinical translation in the future, creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

OPN silencing reduces hypoxic pulmonary hypertension via PI3K-AKT-induced protective autophagy.

Hypoxic pulmonary hypertension (HPH) is a pulmonary vascular disease primarily characterized by progressive pulmonary vascular remodeling in a hypoxic environment, posing a significant clinical challenge. Leveraging data from the Gene Expression Omnibus (GEO) and human autophagy-specific databases, osteopontin (OPN) emerged as a differentially expressed gene, upregulated in cardiovascular diseases such as pulmonary arterial hypertension (PAH). Despite this association, the precise mechanism by which OPN regulates autophagy in HPH remains unclear, prompting the focus of this study. Through biosignature analysis, we observed significant alterations in the PI3K-AKT signaling pathway in PAH-associated autophagy. Subsequently, we utilized an animal model of OPNfl/fl-TAGLN-Cre mice and PASMCs with OPN shRNA to validate these findings. Our results revealed right ventricular hypertrophy and elevated mean pulmonary arterial pressure (mPAP) in hypoxic pulmonary hypertension model mice. Notably, these effects were attenuated in conditionally deleted OPN-knockout mice or OPN-silenced hypoxic PASMCs. Furthermore, hypoxic PASMCs with OPN shRNA exhibited increased autophagy compared to those in hypoxia alone. Consistent findings from in vivo and in vitro experiments indicated that OPN inhibition during hypoxia reduced PI3K expression while increasing LC3B and Beclin1 expression. Similarly, PASMCs exposed to hypoxia and PI3K inhibitors had higher expression levels of LC3B and Beclin1 and suppressed AKT expression. Based on these findings, our study suggests that OPNfl/fl-TAGLN-Cre effectively alleviates HPH, potentially through OPN-mediated inhibition of autophagy, thereby promoting PASMCs proliferation via the PI3K-AKT signaling pathway. Consequently, OPN emerges as a novel therapeutic target for HPH.

Exploring the Mechanism of Zhishi-Xiebai-Guizhi Decoction for the Treatment of Hypoxic Pulmonary Hypertension based on Network Pharmacology and Experimental Analyses.

BACKGROUND: Hypoxic Pulmonary Hypertension (HPH), a prevalent disease in highland areas, is a crucial factor in various complex highland diseases with high mortality rates. Zhishi-Xiebai-Guizhi decoction (ZXGD), traditional Chinese medicine with a long history of use in treating heart and lung diseases, lacks a clear understanding of its pharmacological mechanism. OBJECTIVE: This study aimed to investigate the pharmacological effects and mechanisms of ZXGD on HPH. METHODS: We conducted a network pharmacological prediction analysis and molecular docking to predict the effects, which were verified through in vivo experiments. RESULTS: Network pharmacological analysis revealed 51 active compounds of ZXGD and 701 corresponding target genes. Additionally, there are 2,116 targets for HPH, 311 drug-disease co-targets, and 17 core-targets. GO functional annotation analysis revealed that the core targets primarily participate in biological processes such as apoptosis and cellular response to hypoxia. Furthermore, KEGG pathway enrichment analysis demonstrated that the core targets are involved in several pathways, including the phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway and Hypoxia Inducible Factor 1 (HIF1) signaling pathway. In vivo experiments, the continuous administration of ZXGD demonstrated a significant improvement in pulmonary artery pressure, right heart function, pulmonary vascular remodeling, and pulmonary vascular fibrosis in HPH rats. Furthermore, ZXGD was found to inhibit the expression of PI3K, Akt, and HIF1α proteins in rat lung tissue. CONCLUSION: In summary, this study confirmed the beneficial effects and mechanism of ZXGD on HPH through a combination of network pharmacology and in vivo experiments. These findings provided a new insight for further research on HPH in the field of traditional Chinese medicine.

Bidirectional modulation of extracellular vesicle-autophagy axis in acute lung injury: Molecular mechanisms and therapeutic implications.

Acute lung injury (ALI), a multifactorial pathological condition, manifests through heightened inflammatory responses, compromised lung epithelial-endothelial barrier function, and oxidative stress, potentially culminating in respiratory failure and mortality. This study explores the intricate interplay between two crucial cellular mechanisms-extracellular vesicles (EVs) and autophagy-in the context of ALI pathogenesis and potential therapeutic interventions.EVs, bioactive membrane-bound structures secreted by cells, serve as versatile carriers of molecular cargo, facilitating intercellular communication and significantly influencing disease progression. Concurrently, autophagy, an essential intracellular degradation process, maintains cellular homeostasis and has emerged as a promising therapeutic target in ALI and acute respiratory distress syndrome.Our research unveils a fascinating "EV-Autophagy dual-drive pathway," characterized by reciprocal regulation between these two processes. EVs modulate autophagy activation and inhibition, while autophagy influences EV production, creating a dynamic feedback loop. This study posits that precise manipulation of this pathway could revolutionize ALI treatment strategies.By elucidating the mechanisms underlying this cellular crosstalk, we open new avenues for targeted therapies. The potential for engineered EVs to fine-tune autophagy in ALI treatment is explored, alongside innovative concepts such as EV-based vaccines for ALI prevention and management. This research not only deepens our understanding of ALI pathophysiology but also paves the way for novel, more effective therapeutic approaches in critical care medicine.