Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

Based on a letrozole-induced rat model of polycystic ovary syndrome (PCOS), serum metabolomics was employed to characterize metabolic abnormalities, identify potential biomarkers, and investigate their roles in the pathogenesis and progression of PCOS. Metabolomic analyses revealed significantly decreased levels of cholesterol, pregnenolone, leucine, and citrate in the serum of model rats, accompanied by elevated levels of androsterone glucuronide (ADTG) and linoleic acid, indicating dysregulation of key pathways including steroid biosynthesis, branched-chain amino acid metabolism, tricarboxylic acid (TCA) cycle, and lipid metabolism. To elucidate the tissue origins and molecular mechanisms underlying these metabolic alterations, ovarian proteomics and qRT-PCR analyses were further integrated. The results confirmed the upregulation of key enzymes involved in the related metabolic pathways, such as 17α-hydroxylase (CYP17A1), 11β-hydroxysteroid dehydrogenase (HSD11B1), branched-chain amino acid aminotransferase (BCAT2), fatty acid desaturase 2 (FADS2), and oxoglutarate dehydrogenase (OGDH). These findings suggest that both “cholesterol precursor depletion-androgen accumulation” and “energy/lipid metabolic reprogramming” constitute core features of metabolic disturbances in PCOS. Through multi-omic cross-validation, six serum metabolites with high stability and clinical translational potential were identified as promising combinational biomarkers for the auxiliary diagnosis of PCOS. This study employed a metabolomics-guided strategy, supported by proteomic and transcriptomic validation, which has not only deepened our understanding of PCOS metabolic mechanisms but also provided us with a theoretical foundation for its auxiliary diagnosis.

Objective To investigate the inhibitory effect of Scutellaria baicalensis combined with 5-Fu on Lewis tumor bearing mouse lung cancer based on the JAK2/STAT3 signaling pathway.Methods To detect the changes in body mass,food intake and tumor volume of Lewis tumor-bearing mice after intervention of Scutellaria baicalensis(20 mg/kg)combined with 5-Fu.Pathological changes in tumor tissue were observed by HE staining,expression levels of proliferation related protein Ki67 were observed by immunohistochemical staining,changes in cell apoptosis levels in tumor tissue were observed by TUNEL staining,and changes in expression levels of JAK2,p-JAK2,STAT3,and p-STAT3 proteins in tumor tissue were observed by immunohistochemical staining.Results Compared with the model group,the tumor volume of mice after combined intervention significantly decreased(P＜0.01)and body mass increased(P＜0.05),but there was no significant change food intake.The expression of proliferation related protein Ki67 in tumor tissue was significantly reduced,and the number of apoptotic cells labeled with TUNEL was significantly increased;The expression of p-JAK2 and p-STAT3 proteins is elevated.Conclusions Scutellaria baicalensis decoction can inhibit the JAK2/STAT3 signaling pathway and increase the inhibitory effect of 5-Fu on mouse lung cancer.

Objective To investigate the inhibitory effect of Scutellaria baicalensis combined with 5-Fu on Lewis tumor bearing mouse lung cancer based on the JAK2/STAT3 signaling pathway.Methods To detect the changes in body mass,food intake and tumor volume of Lewis tumor-bearing mice after intervention of Scutellaria baicalensis(20 mg/kg)combined with 5-Fu.Pathological changes in tumor tissue were observed by HE staining,expression levels of proliferation related protein Ki67 were observed by immunohistochemical staining,changes in cell apoptosis levels in tumor tissue were observed by TUNEL staining,and changes in expression levels of JAK2,p-JAK2,STAT3,and p-STAT3 proteins in tumor tissue were observed by immunohistochemical staining.Results Compared with the model group,the tumor volume of mice after combined intervention significantly decreased(P＜0.01)and body mass increased(P＜0.05),but there was no significant change food intake.The expression of proliferation related protein Ki67 in tumor tissue was significantly reduced,and the number of apoptotic cells labeled with TUNEL was significantly increased;The expression of p-JAK2 and p-STAT3 proteins is elevated.Conclusions Scutellaria baicalensis decoction can inhibit the JAK2/STAT3 signaling pathway and increase the inhibitory effect of 5-Fu on mouse lung cancer.

OBJECTIVE To investigate the effect and mechanism of gracillin from Reineckia carnea on autophagy in non- small cell lung cancer A549 cells. METHODS Using A549 cells as subjects， the effects of different concentrations of gracillin （0.25， 0.5， 1， 2， 4 μmol/L） on the proliferation of cells were detected by CCK-8 after being treated for different time （12， 24， 48 h）. Compared with the control group without medication， the effect of gracillin （2 μmol/L） on the formation of autophagosomes in cells was observed by transmission electron microscope after 24 h of exposure. The aggregation of GFP-LC3 on autophagosome membrane was detected by GFP-LC3 plasmid transfection after being treated with gracillin （0.25， 0.5， 1， 2 μmol/L） for 24 h. Quantitative real-time PCR and Western blot assay were used to detect the mRNA and protein expressions of family with sequence similarity 102 member A（FAM102A）， the expressions of autophagy-related proteins [p62， Beclin-1， microtubule-associated protein 1 light chain 3B （LC3B）]， and the expressions of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway-related proteins in A549 cells after being treated with gracillin （0.25， 0.5， 1 and 2 μmol/L） for 24 h. RESULTS Gracillin significantly inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. The IC50 was 2.55 μmol/L at 24 h. After 24 h of gracillin treatment， autophagosomes with bilayer membrane structure were found in the cell cytoplasm， and GFP-LC3 green fluorescent spots on autophagosome membrane were obvious， representing an increasing trend as drug concentration. Compared with the control group， mRNA and protein expressions of FAM102A （0.5， 1， 2 μmol/L groups）， protein expression of Beclin-1 （1， 2 μmol/L groups） and LC3B-Ⅱ/LC3B-Ⅰ ratio （2 μmol/L group） were significantly increased in different concentrations of gracillin groups， while the protein expression of p62 （1， 2 μmol/L groups）， and the protein phosphorylations of Akt （1， 2 μmol/L groups） and PI3K （2 μmol/L group） were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Gracillin can promote excessive autophagy in A549 cells by up-regulating mRNA and protein expressions of FAM102A and inhibiting PI3K/Akt signaling pathway， thus inhibiting cell proliferation.

Objective:To investigate the types and number of symptom clusters in patients undergoing sphincter-preserving surgery for rectal cancer and explore the influencing factors of these symptom clusters.Methods:Totally 192 patients who underwent sphincter-preserving surgery for rectal cancer in the Department of General Surgery at Peking University Third Hospital between January 2021 and January 2023 were selected by convenience sampling. A general information questionnaire, Post-sphincter-preserving Surgery Symptom Questionnaire, and the International Physical Activity Questionnaire-Short Form (IPAQ-SF) were used for data collection.Results:A total of 192 questionnaires were distributed, with 159 valid questionnaires returned. Exploratory factor analysis on 18 symptoms with an incidence rate of over 10.0% identified five primary symptom clusters: the psychological symptom cluster, increased defecation cluster, fatigue-pain cluster, sleep disturbance cluster, and constipation-related cluster. Logistic regression analysis showed that postoperative duration was an influencing factor for the psychological symptom cluster ( P<0.05) ; preoperative radiotherapy and postoperative duration were influencing factors for the increased defecation cluster ( P<0.05) ; postoperative chemotherapy was an influencing factor for the fatigue-pain cluster ( P<0.05) ; and weekly sedentary time was an influencing factor for the sleep disturbance cluster ( P<0.05) . Conclusions:Patients undergoing sphincter-preserving surgery for rectal cancer experience multiple symptom clusters. Preoperative radiotherapy and prolonged sedentary behavior increase the risk of symptom clusters, and different postoperative periods are associated with varying risks for different symptom clusters. However, physical activity levels do not appear to influence the occurrence of symptom clusters. Healthcare providers should implement targeted interventions based on the symptom clusters and their influencing factors to reduce the incidence of symptoms in patients.

As a reversible and dynamic epigenetic marker, N⁶-adenylate methylation (m⁶A) modification is the most common mRNA modification in eukaryotes. This paper briefly described how m⁶A can influence RNA splicing, stability, and translation after transcription, and then participate in a variety of signaling pathways and biological and pathological processes, regulating cell proliferation, apoptosis, epithelial mesenchymal transformation (EMT) processes, and tumor invasion and metastasis. In addition, according to current studies, m⁶A methyltransferases (writers) are believed to promote EMT and tumor development, and readers and erasers both promote and inhibit EMT in different research objects. In this review, we summarized the mechanism of m⁶A modification and its role in cell transformation, and pointed out the direction of disease treatment.

Malignant tumors are diseases that seriously threaten human health and social development. Traditional tumor therapies such as surgery, radiotherapy, chemotherapy and targeted therapy cannot fully meet the needs of clinical treatment, and emerging immunotherapy has become a research hotspot in the field of tumor treatment. Immune checkpoint inhibitors (ICIs) have been approved as a tumor immunotherapy method for the treatment of various tumors, such as lung cancer, liver cancer, stomach cancer and colorectal cancer, etc. However, during the clinical use of ICIs, only a small number of patients experienced durable responses, which also led to drug resistance and adverse reactions. Therefore, the identification and development of predictive biomarkers is crucial to improve the therapeutic efficacy of ICIs. The predictive biomarkers of tumor ICIs mainly include tumor biomarkers, tumor microenvironment biomarkers, circulation-related biomarkers, host environmental biomarkers and combinatorial biomarkers. They are of great significance for screening, individualized treatment and prognosis evaluation of tumor patients. This article reviews the advances of predictive markers for tumor ICIs therapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms ; Biomarkers ; Immunotherapy/methods* ; Biomarkers, Tumor/genetics* ; Prognosis ; Tumor Microenvironment

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.
Humans ; Female ; Biomarkers, Tumor ; Early Detection of Cancer ; Breast Neoplasms/diagnosis* ; Prognosis ; MicroRNAs/genetics*

Background Occupational and environmental particulate matter may cause fibrosis, accompanied by RNA m⁶A modification changes. Neodymium oxide (Nd₂O₃) can cause mouse lung fibrosis, which contains a large number of fibroblasts. Objective To investigate m⁶A modification of tumor necrosis factor receptor-associated protein 6/nuclear factor-κB (TRAF6/NF-κB) signaling pathway in fibrosis of human embryonic lung fibroblasts induced by Nd₂O₃, and identify the key m⁶A modification sites of TRAF6. Methods Designed concentrations of Nd₂O₃ (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100, and 200 mg∙L⁻¹) were infected with HELF cells for 24 and 48 h, and cell viability was detected to determine exposure time and dose. Measurements included indicators of fibrosis [hydroxyproline (HYP) and transforming growth factor-β1 (TGF-β1)], m⁶A methylation level, methyltransferases (METTL3 and METTL14), demethylases (FTO and ALKBH5), reading proteins (YTHDC2 and YTHDF2), fibrosis-associated genes (collagen-І, vimentin, and α-SMA), and proteins related to signaling pathway (TRAF6, NFKB1, P65, and P-P65). The enrichment of m⁶A in TRAF6 mRNA was measured by methylated RNA immunoprecipitation-quantitative real-time PCR (MeRIP-qPCR). Results The results of cell viability indicated that 6.25, 12.5, 25 mg∙L⁻¹ Nd₂O₃ and 48 h exposure time were used for subsequent experiments. After 48 h exposure, compared with the control group, the HYP level in the 25 mg∙L⁻¹ Nd₂O₃ group was increased, and the levels of TGF-β1 in the 6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃ groups were increased (P<0.05); the overall m⁶A methylation levels of HELF cells in the 12.5 and 25 mg∙L⁻¹ Nd₂O₃ groups were increased (P<0.05). At mRNA level, compared with the control group, the mRNA expression levels of methyltransferases METTL3 and METTL14 (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the mRNA expression level of reading protein YTHDF2 (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) was increased (P<0.05), while the mRNA expression level of YTHDC2 (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the mRNA expression levels of demethylases FTO (12.5 and 25 mg∙L⁻¹ Nd₂O₃) and ALKBH5 (25 mg∙L⁻¹ Nd₂O₃) were decreased (P<0.05); the mRNA expression levels of fibrosis-related genes vimentin, α-SMA, and collagen-Ⅰ (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the mRNA expression levels of pathway-related genes TRAF6 (25 mg∙L⁻¹ Nd₂O₃) and NFKB1 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05). At protein level, compared with the control group, the expression levels of methyltransferases METTL3 (25 mg∙L⁻¹ Nd₂O₃) and METTL14 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the expression level of reading protein YTHDF2 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) was increased, while the expression level of YTHDC2 (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the expression level of demethylase FTO (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the expression level of fibrosis-associated protein vimentin was increased at 25 mg∙L⁻¹ Nd₂O₃, and the expression levels of α-SMA and collagen-Ⅰ were increased at 12.5 and 25 mg∙L⁻¹ Nd₂O₃ (P<0.05); the expression levels of TRAF6 and P-P65 were increased at 25 mg∙L⁻¹ Nd₂O₃ (P<0.05). The MeRIP-qPCR results showed that compared with the control group, the concentrations of m⁶A in all Nd₂O₃ groups were significantly increased (P<0.05). Conclusions Upon exposure of HELF cells to Nd₂O₃, the alterations in fibrosis-related indexes increase the expression of some m⁶A methylases and decrease the expression of demethylases, thereby increasing the m⁶A methylase level, and may promote the progression of fibrosis by activating the TRAF6/NF-κB signaling pathway.