OBJECTIVE： To investigate association between short-term exposure to size-specific ultrafine particles and risk of pediatric pneumonia. METHODS： Data between 2015—2020 were collected on emergency visits for pneumonia in children aged 0~14 years from Beijing Children's Hospital and China-Japan Friendship Hospital. Concurrent monitoring of particle number concentrations (PNC) in size fractions of 5-560 nm，conventional air pollutants，and meteorological data from fixed monitoring stations were collected. A time-stratified case-crossover study design and conditional logistic regression models were used to analyze associations between the exposure and pediatric emergency visits，with stratified analyses by age，gender，and season of visit. RESULTS： The short-term exposures were associated with increased risk of emergency visits for pneumonia in the children. An interquartile range (IQR) increment in PNC_5-25，PNC_25-100，PNC_100-560，and UFP exposure in the cumulative lag 0~7 days was associated with increased risks of emergency visits for pneumonia of 11.3% [OR=1.113，95%CI (1.063，1.164)]，21.8% [OR=1.218，95%CI (1.159，1.280)]，7.0% [OR=1.070，95%CI (1.037，1.104)]，and 20.0% [OR=1.200，95%CI (1.143，1.260)]，respectively. Stratified analysis showed that the effect of ambient particles on risk of the emergency visits was more pronounced during the cold season. For every interquartile range increase in the cumulative lag 0~7 days exposure concentration，the risk of pneumonia emergency visits rises by 24.2% [OR=1.242，95%CI (1.178，1.309)]. CONCLUSION： Short-term exposure to ambient particles in size fractions of 5-560 nm，particularly ultrafine particles，was associated with increased risk of pediatric pneumonia in urban area.

OBJECTIVE： To investigate the protective effects and underlying mechanisms of caffeic acid phenethyl ester (CAPE) against acute lung injury induced by exposure to the blister agent 2-chloroethyl ethyl sulfide (CEES) in mice. METHODS： Forty male C57BL/6 mice were exposed to 10% CEES via aerosol inhalation to induce an acute lung injury model. The mice were treated with CAPE (10 mg/kg) at 1，25，and 49 hours post-exposure. Respiratory time (Ti)，expiratory time (Te)，relaxation time (Tr)，and minute ventilation (MVb) were measured on the third day post-exposure as indicators of lung function. Subsequently，the mice were euthanized，and serum and lung tissues were collected to assess body mass and lung-to-body weight ratio. Histopathological examination was performed after hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels in lung tissues were detected using a DHE fluorescent probe. Malondialdehyde (MDA) content，catalase (CAT) activity，and superoxide dismutase (SOD) activity were measured using commercial kits. The mRNA expression levels of antioxidant molecule CAT and inflammatory molecules TNF-α and IL-6 in lung tissues were determined by RT-qPCR. The concentrations of serum inflammatory cytokines TNF-α and IL-6 were measured using ELISA kits. RESULTS： Compared with mice in the CEES-exposed group，mice in the CAPE-treated group exhibited significant recovery in lung function indices，including Ti，Te，Tr，and MVb (all P<0.05)，after 3 days of CEES aerosol inhalation. The degree of pathological damage in lung tissues was reduced. Concurrently，the levels of ROS and MDA in the lung tissue were significantly decreased，accompanied by increased levels of CAT and SOD (all P<0.05). Furthermore，the concentrations of TNF-α and IL-6 in both the lung tissue and serum in the CAPE-treated group were significantly lower than those in the CEES-exposed group (all P<0.05). CONCLUSION： CAPE effectively alleviated CEES-induced acute lung injury in mice through its anti-inflammatory and antioxidant properties，suggesting its potential as a therapeutic candidate for vesicant agent poisoning. This study provides a foundation for the investigation of interventional measures and potential therapeutic drugs for the treatment of vesicant agent poisoning.

OBJECTIVE： To investigate whether premature aging occurs after irradiation of human microvascular endothelial cells (HMEC-1) with ionizing radiation and the mechanism of its generation. METHODS： HMEC-1 cells were irradiated with X-rays at a dose rate of 11.79 mGy/s for 0，2 and 4 Gy，for 0，2.83 and 5.65 min，respectively，and cultured for 24，48 and 72 h after irradiation. The CCK-8 kit was used to detect the changes in cell viability after exposure to ionizing radiation；the β-galactosidase staining kit was used to detect the onset of cellular senescence after irradiation；Giemsa staining was used to observe the changes in the morphology of irradiated cells；and the expression levels of the senescence marker proteins，P53 and P21，were detected using the Western blot method. RESULTS： Compared with the unirradiated group，cell viability decreased significantly at 0 h after irradiation in the 4 Gy dose group (P<0.05)；cell viability decreased significantly at 24，48 and 72 h after irradiation in the 2 and 4 Gy X-ray irradiation groups (P<0.01)；and β-galactosidase staining of the cells at 72 h after irradiation in the 2 and 4 Gy X-rays irradiation groups increased significantly compared with the unirradiated group (P<0.05). And compared with the non-senescent cells，the morphology of the cells that underwent premature senescence became larger，and with the increase of irradiation dose，the more obvious the changes in cell morphology；compared with the non-irradiated group，the expression level of cellular senescence-related proteins P53 and P21 in the irradiated group was significantly elevated (P<0.05). CONCLUSION： Ionizing radiation can cause premature senescence of HMEC-1 cells by activating the P53-P21 pathway.

OBJECTIVE： This study aimed to investigate the effects from exposure to perfluorobutanesulfonic acid (PFBS) on the neurodevelopment of rat offspring. METHODS： Maternal rats were divided into PFBS low (5 mg/kg)，medium (50 mg/kg)，high (500 mg/kg) dose groups and control group (saline). The rats were dosed from the second day of pregnancy (GD1) until weaning. At 90 days after birth，10 offspring from each group were randomly selected for sacrificing，and the hippocampal tissue was collected for pathological，Western blot，and real-time qPCR tests. Pathological test was used to observe the impair of CA1 of hippocampus by subjecting to hematoxylin-eosin (HE) staining. Protein expression of BDNF，TRKB，PI3K，AKT and P-AKT in hippocampus were detected by Western blot. The expression level of Syn1 and Syp mRNA in hippocampus were detected by quantitative reverse transcription PCR. RESULTS： The pathological test showed that early-life exposure to PFBS resulted in the nuclear condensation，blurred cell boundaries，and irregular cell morphology in the CA1 region of hippocampus in each dose groups，most significant in the high dose group. Compared to the control group，protein expression of BDNF，TRKB，PI3K，P-AKT and the ratio of P-AKT/AKT were decreased in each dose group (P<0.01). Expression levels of Syn1 and Syp mRNA decreased in the medium and high dose groups，compared to control group (P<0.05). CONCLUSION： Exposed to PFBS during early life damaged the hippocampus. Damage from PFBS on the BDNF/TRKB/CREB and PI3K/AKT signaling pathways might be the mechanisms for induction of developmental neurotoxicity in rats.

OBJECTIVE： The aims were to study effect of an inhalation blister agent，2-chloroethyl ethyl sulfide (CEES)，on the pulmonary function of mice by the whole body plethysmography (WBP) technology，and to provide an etiological evaluation of lung injury caused by the agent. METHODS： Male C57BL/6 mice were randomly divided into control and CEES exposure groups. The exposure group was given an aerosolized 8% CEES solution，while the control group was expose to an equal dose of solvent ethanol. The daily activity of the mice was monitored，and after 72 hours，the body weights were recorded. WBP was applied to non-invasively detect differences in various lung function characteristics，general indicators，tidal volume，conductivity indicators，airway resistance indicators，ventilation indicators，and minute ventilation. Hematoxylin-eosin (HE) staining was used to detect pathological changes in lung tissue. RESULTS： Compared with control mice，the CEES-exposed group showed reduced activity and a significant decrease in body weight；rate of achieving peak expiratory flow，peak-inspiratory-flow，frequency，and minute volume decreased (P<0.01)；inspiration time，expiration-time，end-inspiratory-pause，time of pause at end of expiration，pause enhanced，and pause increased (P<0.01)；compressed lung alveolar structures，thickened lung septa，infiltration of inflammatory cells in the lung tissue，and entrance of red blood cells into the alveoli. CONCLUSION： Inhalation of blister agents led to increased inspiratory and expiratory bidirectional resistance，prolonged ventilation intervals，decreased respiratory rate，and pulmonary hypoventilation. These may be characteristics of blister agent-induced lung injury.

OBJECTIVE： Paclitaxel resistance (PR) is a significant reason for chemotherapy failure in triple-negative breast cancer (TNBC). This study investigated the sensitizing effect of glycyrrhetinic acid (GA) on paclitaxel (PTX) resistant cells in TNBC and its mechanism of action. METHODS： PTX-resistant TNBC cell lines，MDA-MB-231 and BT-20， were used. Cells were divided into PTX treatment groups and low，medium，and high-dose GA combined groups (PTX treatment plus 2.5，5 or 10 μmol/L GA). Cell viability was assessed using the Sulforhodamine B colorimetric assay. In addition，cells were divided into DMSO control group，40 nmol/L PTX treatment group，10 μmol/L GA treatment group，and 40 nmol/L PTX and 10 μmol/L GA combined group. Colony formation assay was performed to detect cell proliferation，and flow cytometry was used to detect cell apoptosis. Western blot experiments were conducted to measure the protein levels of Bcl-2，Bax，c-PARP，OGT，and MDH1. RESULTS： MDA-MB-231 were treated with 2.5，5 and 10 μmol/L GA combined with PTX for 5 days. The results of sulforhodamine B colorimetric assay showed that compared with the PTX group，the combined treatment led to a decrease in the viability of the cells in a dose-dependent manner. The results of cell colony formation assay showed that compared with the control group，the colony formation rate of cells in the combined treatment group was reduced. Flow cytometry results showed that compared with the PTX group，the proportion of subG₁ group cells increased after the combined treatment for 48 and 72 h. Western blot experiments showed that the expression level of Bcl-2 protein in the combined treatment group was reduced，and the expression levels of Bax and c-PARP proteins were increased. Western blot results showed that the combined treatment significantly inhibited O-GlcNAcylation glycosylation modification，and OGT and MDH1 protein expression levels. CONCLUSION： Glycyrrhetinic acid significantly enhanced the sensitivity of TNBC PTX-resistant cells to paclitaxel by inhibiting the OGT-MDH1 signaling pathway.

OBJECTIVE： To investigate the role of circular RNA homeodomain interacting protein kinase 3 (circHIPK3) in triple-negative breast cancer (TNBC) cell invasion. METHODS： From January 2022 to June 2023，40 cases of surgically removed TNBC tissues，40 cases of non-triple negative breast cancer tissues and 40 cases of corresponding paracancer tissues were collected. Expression level of circHIPK3 was detected by fluorescence quantitative PCR. Normal human mammary epithelial cell lines MCF10A，non-triple negative breast cancer cell lines MCF-7 and SK-BR-3，TNBC cell lines HCC1806，MDA-MB-231 and HCC-70 were cultured.，Their expression levels of circHIPK3 were detected by fluorescence quantitative PCR. According to the expression level，MDA-MB-231 cells with the highest circHIPK3 expression were selected for grouping. The siRNA sequence with the most significant circHIPK3 knockdown effect was screened，and then circHIPK3 siRNA and miR-485-3 were co-transfected into MDA-MB-231 cells. Expressions of circHIPK3 and miR-485-3p were detected by fluorescence quantitative PCR. Protein expression of FGF2 was detected by western blot. The number of cell invasions was detected by the transwell invasion assay. RESULTS： The relative expression levels of circHIPK3 in breast cancer tissues were higher than that in adjacent tissues (P<0.05). The relative expression level of circHIPK3 in TNBC tissues was higher than that in non-triple negative breast cancer tissues (P<0.05). The relative expression level of circHIPK3 in TNBC cell lines was higher than that in non-triple negative breast cancer cell lines and normal breast cancer epithelial cell lines (P<0.05)，and the expression level of circHIPK3 in MDA-MB-231 cells was higher than that in HCC1806 and HCC-70 cells (P<0.05). Compared with the cells transfected with control siRNA sequence，the expression levels of circHIPK3 and FGF2 and the number of cell invasion in MDA-MB-231 cells transfected with circHIPK3 siRNA were decreased，and the expression level of miR-485-3p was increased (P<0.05). Compared with cells transfected with miRNA control sequences，the expression level of miR-485-3p in MDA-MB-231 cells transfected with miR-485-3p (co-transfected with circHIPK3 siRNA) was decreased，and the expression level of FGF2 and the number of cell invasion were increased (P<0.05). CONCLUSION： CircHIPK3 promoted TNBC cell invasion and a possible mechanism is via promotion of the FGF2 protein expression by inhibiting the expression of miR-485-3p.

OBJECTIVE： To investigate expression of the cuproptosis related gene COX17，in esophageal cancer and its impact on cellular function. METHODS： Correlations between COX17 mRNA and clinical characteristics of esophageal cancer patients were evaluated using the UALCAN database. Immunohistochemistry was used to detect the expression of COX17 in 15 pairs of esophageal cancer and their corresponding adjacent tissues，and clinical pathological data was analyzed. siRNA interference was used to knock down the expression of COX17 in esophageal cancer cell line Eca109. The knockdown effect on siR-COX17 was detected by Western blot，and the effects of COX17 downregulation on the proliferation，migration，and invasion ability of Eca109 cells were detected by CCK-8 assay，scratch assay，and transwell assay. RESULTS： The UALCAN data analysis showed that，compared with the normal control group，expression of COX17 was significantly increased in esophageal cancer，and its expression level was correlated with tumor clinical stage，pathological grading，gender，age，and race (P<0.05). The immunohistochemical detection showed that the expression of COX17 was higher in esophageal cancer tissues than in corresponding adjacent tissues，and the expression level of COX17 was significantly correlated with pathological grading and lymph node metastasis (P<0.05). After siRNA transfection，the expression level of COX17 protein in Eca109 was significantly lower than that in the control group，and the knock down inhibited the proliferation，migration，and invasion ability of esophageal cancer cells. CONCLUSION： The cuproptosis related gene COX17 was highly expressed in esophageal cancer and was associated with prognosis，which mignt be involved in the malignant progression of esophageal cancer.

OBJECTIVE： To investigate the expression and prognostic value of subtype 8 of the zinc finger domain containing myeloid neurodegenerative epidermal growth factor (ZMYND8) in adult glioma. METHODS： Immunohistochemistry was used to detect the expression level of ZMYND8 in 104 adult glioma tissues， and the relationship between ZMYND8 expression and prognosis of glioma patients was evaluated by receiver operating characteristic (ROC) curve prediction efficiency. Kaplan-Meier survival was used to analyze the relationship between ZMYND8 expression and overall survival (OS) of adult human glioma patients. Cox regression was used to analyze factors affecting the survival of patients with glioma after surgery. RESULTS： The immunohistochemical results showed that the expression of ZMYND8 protein in glioma was higher than that in normal brain tissue (P<0.05)，and the high expression rate in high-grade glioma was significantly higher than that in low-grade glioma (P<0.05). The expression of ZMYND8 was correlated with pathological classification and WHO grade (P<0.01)，but not with sex，age，tumor site，tumor diameter，and Karnofsky (KPS) score. Kaplan-Meier survival analysis showed that the OS of glioma patients with high expression of ZMYND8 was significantly lower than that of glioma patients with low expression (Log-rank P<0.01). Multivariate Cox regression analysis showed that age and WHO grade were independent factors of glioma OS. CONCLUSION： The expression of ZMYND8 was increased in adult glioma patients and the increase was related to the degree of malignancy and prognosis. Thus，ZMYND8 can be used as a potential marker for the diagnosis and prognosis of glioma.

OBJECTIVE： To explore whether glycyrrhizic acid has an anti-lung adenocarcinoma effect and its mechanism in vitro. METHODS： Human lung adenocarcinoma cells A549，NCI-H1299，normal human lung epithelial cells Beas-2b，and human umbilical vein endothelial cells (HUVECs) were treated with glycyrrhizic acid at concentrations of 0.5-6 mmol/L for 48 hours. The MTT assay was used to detect effects on growth and viability. Flow cytometry was used to assess effects on cell cycle and apoptosis in A549 cells，comparing the untreated with cells treated with 4 mmol/L glycyrrhizic acid. Network pharmacology was employed to predict key targets and pathways impacted by glycyrrhizic acid. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to verify key targets after treatment with 4 mmol/L glycyrrhizic acid in A549 cells. RESULTS： At concentrations of 1-6 mmol/L，glycyrrhizic acid significantly inhibited the viability of A549 and NCI-H1299 cells，while showing a weaker inhibitory effect on normal lung epithelial cells Beas-2b and HUVECs. After treatment with 4 mmol/L glycyrrhizic acid，the proportion of apoptotic cells in the control group was (3.73±1.43)%，compared to (44.41±10.28)% in the treatment group. The proportion of cells in the G₀/G₁ phase in the control group was (45.7±0.98)%，while the treatment group had (53.03±2.25)%. Network pharmacology predicted the key targets were caspase 3，STAT3，SRC，MMP9，and PTGS2，which are involved in apoptosis，cell cycle arrest，and oxidative stress signaling pathways. In addition，glycyrrhizic acid significantly reduced the mRNA expression of SRC and PTGS2 in A549 cells，inhibited the expression of p-STAT3，and activated the cleavage of caspase 3. CONCLUSION： Our in vitro studies indicate that glycyrrhizic acid selectively killed human lung adenocarcinoma cells A549，primarily through the induction of cell cycle arrest and apoptosis，possibly involving downregulation of SRC，PTGS2，and p-STAT3 expression levels and activation of caspase 3.

OBJECTIVE： To explore the effect of miR-let-7a-5p on malignant development of esophageal squamous cell carcinoma (ESCC) by targeting and regulating the synaptosomal-associated protein of 23 kDa (SNAP23). METHODS： From database of Differentially Expressed MiRNAs in human Cancers (dbDEMC)， the expression levels of miR-let-7a-5p in cancer tissues and normal tissues adjacent to tumor were analyzed. From the database of MiRNAs in human Cancers (CancerMIRNome)，Kaplan-Meier survival curve and logarithmic rank test were used to investigate the relationship between the expression level of miR-let-7a-5p and the prognosis of patients with esophagea l cancer. Quantitative real-time reverse transcription-PCR (RT-qPCR) was used to detect the expression of miR-let-7a-5p in the human immortalized esophageal epithelial cell lines，SHEE and ESCC. Lentiviral vector transfection technology was utilized to construct stably transfected cell lines overexpressing miR-let-7a-5p. Cell proliferation was detected by the EdU cell proliferation and clone formation assay. Cell migration was detected by the cell scratch assay. The transwell assay was used to detect cell invasion. The expression of miR-let-7a-5p in peripheral blood of patients with esophageal cancer was analyzed in dbDEMC and CancerMIRNome databases. The downstream target genes of miR-let-7a-5p were searched in ENCORI，Diana Tarbase and miRDB databases. Protein expression of SNAP23 was detected by protein blotting (Western blot)；dual luciferase reporter gene assay was used to analyze the targeting relationship between miR-let-7a-5p and SNAP23. RESULTS： The expression level of miR-let-7a-5p in esophageal cancer tissues was lower than that in adjacent normal tissues，and the expression level was positively correlated with the overall survival of patients (P<0.05). The expression of miR-let-7a-5p in ESCC cell line was lower than that in human immortal SHEE (P<0.01). The proliferation，clone formation，migration and invasion abilities of TE-13 were significantly inhibited by enhanced miR-let-7a-5p expression compared with control (P<0.05 or P<0.01). In peripheral blood of ESCC patients，the expression level of miR-let-7a-5p was increased compared with that of healthy controls. The secreted protein SNAP23 was predicted to be the downstream target gene of miR-let-7a-5p. The protein expression level of SNAP23 decreased after overexpression of miR-let-7a-5p (P<0.01). The results of dual luciferase reporter gene assay showed that miR-let-7a-5p could down-regulate the relative luciferase activity of wild-type SNAP23 (P<0.01). CONCLUSION： miR-let-7a-5p can inhibit the malignant biological behavior of ESCC by down-regulating the expression of SNAP23.