Identification of DNA methylation characteristics associated with metastasis and prognosis in colorectal cancer.

Colorectal cancer (CRC) is prone to metastasis and recurrence after surgery, which is one of the main causes for its poor treatment and prognosis. Therefore, it is essential to identify biomarkers associated with metastasis and recurrence in CRC. DNA methylation has a regulatory role in cancer metastasis, tumor immune microenvironment (TME), and prognosis and may be one of the most valuable biomarkers for predicting CRC metastasis and prognosis. We constructed a diagnostic model and nomogram that can effectively predict CRC metastasis based on the differential methylation CpG sites (DMCs) between metastatic and non-metastatic CRC patients. Then, we identified 17 DMCs associated with progression free survival (PFS) of CRC and constructed a prognostic model. The prognosis model based on 17 DMCs can predict the PFS of CRC with medium to high accuracy. The results of immunohistochemical analysis indicated that the protein expression levels of the genes involved in prognostic DMCs were different between normal and colorectal cancer tissues. According to the results of immune-related analysis, we found that the low-risk patients had better immunotherapy response. In addition, high risk scores were negatively correlated with high tumor mutation burden (TMB) levels, and patients with low TMB levels in the high-risk group had the worst PFS. Our work shows the clinical value of DNA methylation in predicting CRC metastasis and PFS, as well as their correlation with TME, immunotherapy, and TMB, which helps understand the changes of DNA methylation in CRC metastasis and improving the treatment and prognosis of CRC.

Extragonadal germ cell tumors: A clinicopathologic study with emphasis on molecular features, clinical outcomes and associated secondary malignancies.

Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis.

Probiotic-fermented tomato with hepatic lipid metabolism modulation effects: analysis of physicochemical properties, bioactivities, and potential bioactive compounds.

Lactiplantibacillus plantarum NCUH001046 (LP)-fermented tomatoes exhibited the potential to alleviate obesity in our previous study. This subsequent study further delves deeper into the effects of LP fermentation on the physicochemical properties, bioactivities, and hepatic lipid metabolism modulation of tomatoes, as well as the analysis of potential bioactive compounds exerting obesity-alleviating effects. Results showed that after LP fermentation, viable bacterial counts peaked at 9.11 log CFU mL-1 and sugar decreased, while organic acids, umami amino acids, total phenols, and total flavonoids increased. LP fermentation also improved the inhibition capacities of three digestive enzyme activities and Enterobacter cloacae growth, as well as antioxidant activities. Western blot results indicated that fermented tomatoes, especially live probiotic-fermented tomatoes (LFT), showed improved effects compared to unfermented tomatoes in reducing hepatic lipid accumulation by activating the AMPK signal pathway. UHPLC-Q-TOF/MS-based untargeted metabolomics analysis showed that chlorogenic acid, capsiate, tiliroside, irisflorentin, and homoeriodictyol levels increased after fermentation. Subsequent cell culture assays demonstrated that irisflorentin and homoeriodictyol reduced lipid accumulation via enhancing AMPK expression in oleic acid-induced hyperlipidemic HepG2 cells. Furthermore, Spearman's correlation analysis indicated that the five phenols were positively associated with hepatic AMPK pathway activation. Consequently, it could be inferred that the five phenols may be potential bioactive compounds in LFT to alleviate obesity and lipid metabolism disorders. In summary, these findings underscored the transformative potential of LP fermentation in enhancing the bioactive profile of tomatoes and augmenting its capacity to alleviate obesity and lipid metabolism disorders. This study furnished theoretical underpinnings for the functional investigation of probiotic-fermented plant-based foods.

Chromosomal localization of mutated genes in non-syndromic familial thyroid cancer.

Familial non-medullary thyroid carcinoma (FNMTC) is a type of thyroid cancer characterized by genetic susceptibility, representing approximately 5% of all non-medullary thyroid carcinomas. While some cases of FNMTC are associated with familial multi-organ tumor predisposition syndromes, the majority occur independently. The genetic mechanisms underlying non-syndromic FNMTC remain unclear. Initial studies utilized SNP linkage analysis to identify susceptibility loci, including the 1q21 locus, 2q21 locus, and 4q32 locus, among others. Subsequent research employed more advanced techniques such as Genome-wide Association Study and Whole Exome Sequencing, leading to the discovery of genes such as IMMP2L, GALNTL4, WDR11-AS1, DUOX2, NOP53, MAP2K5, and others. But FNMTC exhibits strong genetic heterogeneity, with each family having its own pathogenic genes. This is the first article to provide a chromosomal landscape map of susceptibility genes associated with non-syndromic FNMTC and analyze their potential associations. It also presents a detailed summary of variant loci, characteristics, research methodologies, and validation results from different countries.

Machine Learning Reveals Impacts of Smoking on Gene Profiles of Different Cell Types in Lung.

Smoking significantly elevates the risk of lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. This risk is attributed to the harmful chemicals in tobacco smoke that damage lung tissue and impair lung function. Current research on the impact of smoking on gene expression in specific lung cells is limited. This study addresses this gap by analyzing gene expression profiles at the single-cell level from 43,539 lung endothelial cells, 234,349 lung epithelial cells, 189,843 lung immune cells, and 16,031 lung stromal cells using advanced machine learning techniques. The data, categorized by different lung cell types, were classified into three smoking states: active smoker, former smoker, and never smoker. Each cell sample encompassed 28,024 feature genes. Employing an incremental feature selection method within a computational framework, several specific genes have been identified as potential markers of smoking status in different lung cell types. These include B2M, EEF1A1, and TPT1 in lung endothelial cells; FTL and MT-ATP8 in lung epithelial cells; HLA-B and HLA-C in lung immune cells; and HSP90B1 and LCN2 in lung stroma cells. Additionally, this study developed quantitative rules for representing the gene expression patterns related to smoking. This research highlights the potential of machine learning in oncology, enhancing our molecular understanding of smoking's harm and laying the groundwork for future mechanism-based studies.

Biological functions of PCAT-1/ SOX4 in cell proliferation and invasion of breast cancer.

Breast cancer (BC) is one of the most common fatal cancers. Recent studies have identified the vital role of long noncoding RNA (lncRNAs) in the development and progression of BC. In this research, lncRNA PCAT-1 was studied to identify how it functioned in the metastasis of BC. PCAT-1 expression of tissues was detected by real-time quantitative polymerase chain reaction (RT-qPCR) in 50 BC patients. Cell proliferation, wound healing assay and transwell assay were used to observe the biological behavior changes of BC cells through knockdown or overexpression of PCAT-1. In addition, RT-qPCR and Western blot assay were performed to discover the potential target protein of PCAT-1 in BC. PCAT-1 expression level in BC samples was higher than that of adjacent ones. Besides, cell proliferation, migrated ability and cell invaded ability of BC cells were inhibited after PCAT-1 was silenced. Cell proliferation, migration and invasion of BC cells were promoted after PCAT-1 was overexpressed. In addition, SOX4 was downregulated after silence of PCAT-1 in BC cells, while SOX4 was upregulated after overexpression of PCAT-1 in BC cells. Furthermore, SOX4 was upregulated in BC tissues and was positively associated with PCAT-1. Our study uncovers a new oncogene in BC and suggests that PCAT-1 could enhance BC cell proliferation, migration and invasion via targeting SOX4, which provided a novel therapeutic target for BC patients.

Biological functions of LncRNA SNHG14 in the development of thyroid cancer cells via targeting miR-206.

This study aimed to determine lncRNA SNHG14 and miR-206 in Thyroid Cancer ( TC) and to explore the related mechanisms. Sixty-four samples of thyroid tissue were collected from patients with TC. TC cell lines and a normal human thyroid cell line (HTori-3) were bought. lncRNA SNHG14-siRNA (si-lncRNA SNHG14), lncRNA SNHG14-shRNA (sh-lncRNA SNHG14), blank plasmid (siRNA-NC), miR-206-inhibitor, miR-206-mimics were transfected into BHT101 and Ocut-2C cells. qRT-PCR quantified the expression of lncRNA SNHG14 and miR-206, and the expression of vimentin, Snail, N-cadherin, Slug, E-cadherin and ZO-1 proteins were identified via WB. MTT assay, flow cytometry, and Transwell were employed to determine cellular proliferation, apoptosis, and invasion, separately. The high expression of lncRNA SNHG14 and low expression of miR-206 were exhibited in patients with TC. lncRNA SNHG14 and miR-206 were related to lymph node metastases, TNM staging, as well as differentiation of TC. Silencing lncRNA SNHG14 and over-expressing miR-206 inhibited cell EMT, proliferation, and invasion, but accelerated apoptosis. WB demonstrated that silencing lncRNA SNHG14 and over-expressing miR-206 suppressed the expression of Akt, p-ERK1/2, p-p38, p-4EBP1, p-Akt, PI3K, vimentin, Snail, N-cadherin, and Slugn, as well as up-regulated the expression of E-cadherin and ZO-1. Rescue experiment showed that after BHT101 and Ocut-2C cells were transfected with either sh-lncRNA SNHG14+miR-206-mimics or si-lncRNA SNHG14+miR-206-inhibitor, the cellular proliferative, invasive, and apoptotic activities weren't different from those transfected with siRNA-NC. Suppression of lncRNA SNHG14 up-regulates miR-206 and affects EMT, as well as proliferative, invasive, and apoptotic activities of cells, which may become an underlying treatment target for TC.

Development and validation of HPV-associated and HPV-independent penile squamous cell carcinoma prognostic nomogram.

OBJECTIVE: The aim of this study was to introduce HPV-associated and HPV-independent histologic classifications to analyze prognostic factors and develop a prognostic nomogram for patients with penile squamous cell carcinoma (PSCC). METHODS: Data of 1502 PSCC patients between 2010 and 2020 were accessed from the SEER database, and the patients were randomly divided into a training set and a validation set. Independent risk factors for PSCC patients prognosis were analyzed by using univariate and multivariate COX proportional hazards regression, and was used for the construction of the nomogram, and the predictive performance of the model was evaluated by C-index, calibration curve and ROC curve. Kaplan-Meier analysis was applied to explore the impact of HPV-related factors on patient survival, while propensity score matching (PSM) and inverse probability treatment weighting (IPTW) techniques were used to balance other confounding factors like individual clinical and pathological factors, and to evaluate the differences in overall survival (OS) and cause-specific survival (CSS) between subgroups. RESULT: The results indicated that histologic type, Grade classification, T/M stage, surgical methods and chemotherapy were independent risk factors affecting OS and CSS in PSCC patients. In addition, age and marital status were significantly associated with OS, while lymph node metastasis was an independent prognostic factor for CSS, the validation results of the model showed that the nomogram had a superior predictive performance compared with the American Joint Committee on Cancer staging system. In addition, subgroup analyses prior to and after IPTW and PSM adjustments showed that HPV-associated group had better OS and CSS than HPV-independent group. CONCLUSION: Our study developed and validated a nomogram using a novel histologic classification and achieved satisfactory results, which can better help clinicians to predict the prognosis of penile squamous cell carcinoma patients.

Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates.

Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.

Predicting postoperative prognosis of pancreatic cancer using a computed tomography-based radio-clinical model: exploring biologic functions.

Computed tomography (CT) imaging has the potential to assist in predicting the prognosis and treatment strategies for pancreatic cancer (PC). This study aimed to develop and validate a radio-clinical model based on preoperative multiphase CT assessments to predict the overall survival (OS) of PC and identify differentially expressed genes associated with OS. METHODS: Patients with PC who had undergone radical pancreatectomy (R0 resection) were divided into development and external validation sets. Independent predictors of OS were identified using Cox regression analyses and included in the nomogram, which was externally validated. The area under the curve was used to measure the model's accuracy in estimating OS probability. RNA sequencing data from The Cancer Genome Atlas were used for gene expression analysis. RESULTS: In the development and external validation sets, survival was estimated respectively for 132 and 27 patients. Multivariate Cox regression analysis identified 5 independent OS predictors: age (P = .049), sex (P = .001), bilirubin level (P = .005), tumor size (P = .020), and venous invasion (P = .041). These variables were incorporated into the nomogram. Patients were divided into high- and low-risk groups for OS and survival curves showed that all patients in the low-risk group had better OS than that of those in the high-risk group (P < .001). Differentially expressed genes in patients with a poor prognosis were involved in neuroactive ligand-receptor interaction. CONCLUSION: The radio-clinical model may be clinically useful for successfully predicting PC prognosis.

IgG4-related autoimmune pancreatitis and sclerosing cholangitis: A case report and literature review.

RATIONALE: Immunoglobulin G4-related disease (IgG4-RD) can involve various organs throughout the body, primarily manifesting as endocrine dysfunction, visual impairment, jaundice, and limited sexual function. IgG4-related autoimmune pancreatitis is triggered by autoimmune reactions and characterized by structural changes in the pancreas and pancreatic ducts. The disease mainly affects middle-aged and elderly males, typically presenting as progressive painless jaundice and misdiagnosed as cholangiocarcinoma or pancreatic cancer. PATIENT CONCERNS: This study reports a 54-year-old male who consulted with different institutions multiple times due to diabetes, pancreatitis, elevated liver enzymes, and jaundice. DIAGNOSES: Magnetic resonance imaging revealed swollen head of the pancreas and atrophic tail. Liver and pancreatic tissue pathology showed IgG4 plasma cell infiltration, while liver biopsy indicated interface hepatitis, liver fibrosis, and pseudolobule formation, with no evidence of bile duct damage. INTERVENTIONS: Following hormone therapy, the patient's serum IgG4 levels and liver enzyme levels returned to normal. OUTCOMES: The disease relapsed 2 years after maintaining hormone therapy, and the patient underwent additional hormone-induced remission therapy combined with azathioprine. LESSONS: The purpose of this research report is to enhance the awareness and understanding of IgG4-RD, emphasizing the necessity for personalized treatment strategies that take into account its recurrence, associations, and imaging features. This report provides valuable insights and guidance for clinicians in managing and diagnosing patients with IgG4-RD.

Joint association and interaction of birth weight and lifestyle with hypertension: A cohort study in UK Biobank.

Low birth weight and unhealthy lifestyle are both associated with an increased risk of hypertension. The authors aimed to assess the joint association and interaction of birth weight and lifestyle with incident hypertension. The authors included 205 522 participants free of hypertension at baseline from UK Biobank. A healthy lifestyle score was constructed using information on body mass index, physical activity, diet, smoking status and alcohol intake. Cox proportional hazard models were used to investigate the impact of birth weight, healthy lifestyle score and their joint effect on hypertension. The authors documented 13 548 (6.59%) incident hypertension cases during a median of 8.6 years of follow-up. The multivariate adjusted hazard ratios and 95% confidence intervals were 1.12 (1.09, 1.15) per kg lower birth weight and 0.76 (0.75, 0.77) per score increment in healthy lifestyle score. Healthy lifestyle reduced the risk of hypertension in any category of different birth weight groups. The preventive effect of healthy lifestyle on hypertension was the most pronounced at lower birth weight with <2500 g and 2500-2999 g, respectively. Addictive interaction between birth weight and healthy lifestyle score was observed with the relative excess risk due to interaction of 0.04 (0.03, 0.05). Our findings emphasized the importance of healthy lifestyle for hypertension prevention, especially among the high-risk population with lower birth weight.

Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora.

Four new sesquiterpene lactones (SLs) (1-4), along with a biosynthetically related SL (5), have been isolated from the leaves of Magnolia grandiflora. Magrandate A (1) is notable as the first C18 homogemarane type SL, featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one core. Compounds 2 and 3, representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products, were also identified. The structures of these isolates were elucidated through a combination of spectroscopic data analysis, electronic circular dichroism calculations, and X-ray single-crystal diffraction analysis. All isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells. Notably, 3-5 showed a significant inhibitory effect on nitric oxide production, with IC50 values ranging from 0.79 to 4.73 µmol·L-1. Additionally, 4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines, with IC50 values between 3.09 and 11.23 µmol·L-1.

MORN2 regulates the morphology and energy metabolism of mitochondria and is required for male fertility in mice.

BACKGROUND: Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes. METHODS: We generated Morn2-/- mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc. RESULTS: The Morn2-/- mice were infertile, and their sperm showed severe motility defects. Morn2-/- sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity. CONCLUSIONS: Our study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.

Prognostic value of inflammation and immune-related gene NOD2 in clear cell renal cell carcinoma.

Inflammation and immune responses play important roles in cancer development and prognosis. We identified 59 upregulated inflammation- and immune-related genes (IIRGs) in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas database. Among the upregulated IIRGs, nucleotide binding oligomerization domain 2 (NOD2), PYD and CARD domain (PYCARD) were also confirmed to be upregulated in the Oncomine database and in three independent GEO data sets. Tumor immune infiltration resource database analysis revealed that NOD2 and PYCARD levels were significantly positively correlated with infiltration levels of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells. Multivariate Cox hazards regression analysis indicated that based on clinical variables (age, gender, tumor grade, pathological TNM stage), NOD2, but not PYCARD, was an independent, unfavorable ccRCC prognostic biomarker. Functional enrichment analyses (GSEA) showed that NOD2 was involved in innate immune responses, inflammatory responses, and regulation of cytokine secretion. Meanwhile, mRNA and protein levels of NOD2 were elevated in four ccRCC cell lines (786-O, ACHN, A498 and Caki-1), and its knockdown significantly inhibited IL-8 secretion, thereby inhibiting ccRCC cell proliferation and invasion. Furthermore, results showed that miR-20b-5p targeted NOD2 to alleviate NOD2-mediated IL-8 secretion. In conclusion, NOD2 is a potential prognostic biomarker for ccRCC and the miR-20b-5p/NOD2/IL-8 axis may regulate inflammation- and immune-mediated tumorigenesis in ccRCC.

Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

High levels of cadmium altered soil archaeal activity, assembly, and co-occurrence network in volcanic areas.

Soil microbial communities are essential to biogeochemical cycles. However, the responses of microorganisms in volcanic soil with high heavy metal levels remain poorly understood. Here, two areas with high levels of cadmium (Cd) from the same volcano were investigated to determine their archaeal composition and assembly. In this study, the Cd concentrations (0.32-0.38 mg/ kg) in the volcanic soils exceeded the standard risk screening values (GB15618-2018) and correlated with archaeal communities strongly (P < 0.05). Moreover, the area with elevated levels of Cd (periphery) exhibited a greater diversity of archaeal species, albeit with reduced archaeal activity, compared to the area with lower levels of Cd (center). Besides, stochastic processes mainly governed the archaeal communities. Furthermore, the co-occurrence network was simplest in the periphery. The proportion of positive links between taxa increased positively with Cd concentration. Moreover, four keystone taxa (all from the family Nitrososphaeraceae) were identified from the archaeal networks. In its entirety, this study has expanded our comprehension of the variations of soil archaeal communities in volcanic areas with elevated cadmium levels and serves as a point of reference for the agricultural development of volcanic soils in China.

Protective effect of Xixin-Ganjiang herb pair for warming the lungs to dissolve phlegm in chronic obstructive pulmonary disease rats based on integrated network pharmacology and metabolomics.

Xixin-Ganjiang herb pair (XGHP) is a classic combination for warming the lungs to dissolve phlegm and is often used to treat a variety of chronic lung diseases; it can treat the syndrome of cold phlegm obstruction of lungs. First, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to examine the composition of XGHP, and network pharmacology was used to predict its potential core targets and signaling pathways in the current study. Second, a rat model of chronic obstructive pulmonary disease (COPD) was established for assessing the anti-COPD activity of XGHP, and metabolomics was used to explore the biomarkers and metabolic pathways. Finally, the sample was validated using molecular docking and Western blotting. The integration of metabolomics and network pharmacology results identified 11 targets, 3 biomarkers, 3 pathways, and 2 metabolic pathways. Western blotting showed that XGHP effectively regulated the expression of core proteins via multiple signaling pathways (downregulation of toll-like receptor 4 [TLR4] and upregulation of serine/threonine-protein kinase 1 [p-AKT1] and nitric oxide synthase 3 [NOS3]). Molecular docking results showed that the 10 potentially active components of XGHP have good affinity with tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase 9 (MMP-9), TLR4, p-AKT1, and NOS3. Our findings suggest that XGHP may regulate glucolipid metabolism, improve energy supply, and inhibit inflammatory responses (TNF-α, IL-6, and MMP-9) via the PI3K-Akt signaling pathway and HIF-1 signaling pathway in the management of COPD.