Objective To investigate the effect of resveratrol on airway remodeling induced by ovalbumin(OVA)in asthmatic young mice based on the sphingosine-1-phosphate(S1P)/transforming growth factor-β1(TGF-β1)pathway.Methods Young mice were randomly assigned into normal group,model group,S1P group,resveratrol group,and resveratrol+S1P group,with 12 mice in each group.A mouse model of asthma induced by OVA was established.The Wright Giemsa staining was applied to detect the number of inflammatory cells in bronchoalveolar lavage fluid(BALF).ELISA was applied to detect the levels of interleukin-4(IL),IL-5,and IL-13 in BALF.The colorimetric method was applied to detect the activities of SOD and CAT and the content of MDA in lung tissue.HE staining was applied to observe pathological changes in lung tissue,and the wall area of bronchial tube(Wat)and perimeter of basement membrane(Pbm)were analyzed.Masson staining was applied to observe the area of collagen fibers in lung tissue.Immunohistochemistry was applied to detect the expression of α-SMA in lung tissue.Western blot was applied to detect the expression of E-cadherin,N-cadherin,Snail,SP1,and TGF-β1 proteins in lung tissue.Results Compared with the normal group,the number of eosinophils,lymphocytes,neutrophils,levels of IL-4,IL-5,and IL-13 in BALF,lung tissue MDA content,Wat/Pm ratio,collagen fiber area,α-SMA positive expression,the protein levels of N-cadherin,Snail,SP1,TGF-β1 increased in the model group,while the activities of SOD,CAT,and the protein level of E-cadherin in lung tissue decreased(P＜0.05).Compared to the model group,the number of eosinophils,lymphocytes,neutrophils,levels of IL-4,IL-5,and IL-13 in BALF,lung tissue MDA content,Wat/Pm ratio,collagen fiber area,α-SMA positive expression,the protein levels of N-cadherin,Snail,SP1,TGF-β1 decreased in the resveratrol group,while the activities of SOD,CAT,and the protein level of E-cadherin in lung tissue increased(P＜0.05).The S1P recombinant protein could weaken the inhibitory effect of resveratrol on airway remodeling in asthmatic young mice.Conclusion Resveratrol can inhibit oxidative stress,airway inflammation,and epithelial mesenchymal transition,thereby suppressing airway remodeling in asthmatic young mice.Its effect is related to the inhibition of the S1P/TGF-β1 signaling pathway.

Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.

Objective:To investigate the inflammatory indicator levels and influencing factors on middle-aged and elderly male residents at different residential distances from a uranium mine in Guangdong, so as to provide scientific data for the health risk assessment of the residents therein.Methods:With stratified sampling method, two groups of the permanent middle-aged and elderly male residents were randomly sampled within < 10 km and 10-20 km of the uranium mine, along with the basic demographic characteristics and lifestyle information collected through face-to-face questionnaire survey. Both height and weight of the respondents were measured using standard method and their body mass indexes (BMI) were calculated. Through collection of the venous blood, the levels of a wide range of inflammatory indicators were measured, such as C-reactive protein (CRP), complement C3, complement C4, leukocytes, lymphocytes, neutrophils, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and others. Multiple linear regression was used to analyze the influencing factors on the levels of inflammation indicators.Results:A total of 867 middle-aged and elderly male residents were included in this study, including one group of 431 residents within the 10-20 km at an average age of 51.54±5.37, and a second group of 436 residents within <10 km at an average age of 52.05±5.24. The result of multiple linear regression showed a positive correlation of the distance groups with complement C4 level ( β=0.014, 95% CI: 0.001-0.027) and lymphocyte number ( β=0.086, 95% CI: 0.003-0.168) ( t=2.07, 2.04, P<0.05). The ages of middle-aged and elderly male residents around the uranium mine was positively correlated ( t=2.50, P<0.05) with the levels of complement C4 ( β=0.018, 95% CI: 0.004-0.031), and negatively correlated ( t=-3.25, -2.97, P<0.05) with the levels of TNF-α ( β=-63.022, 95% CI: -101.114 to -24.929) and IL-6 ( β=-14.694, 95% CI: -24.396 to -4.992). Smoking was positively correlated ( t=4.29, 4.81, 3.19, P<0.05) with leukocytes number ( β=0.630, 95% CI: 0.341-0.918), lymphocytes number ( β=0.226, 95% CI: 0.134-0.319) and neutrophils number ( β=0.372, 95% CI: 0.143-0.601), and negatively correlated ( t=-2.07, -1.98, P<0.05) with the levels of TNF-α ( β=-43.551, 95% CI: -84.778 to -2.324) and IL-6 ( β=-10.603, 95% CI: -21.103 to -0.102). BMI was positively correlated ( t=8.60, 3.62, 3.18, 4.01, 2.10, P<0.05) with complement C3 level ( β=0.108, 95% CI: 0.084-0.133), complement C4 level ( β=0.026, 95% CI: 0.012-0.039), leukocytes number ( β=0.433, 95% CI: 0.166-0.699), lymphocyte number ( β=0.175, 95% CI: 0.089-0.261), and neutrophil number ( β=0.226, 95% CI: 0.014-0.438). Fruit consumption ( β=0.017, 95% CI: 0.001-0.034) was positively correlated with complement C4 levels ( t=2.10, P<0.05). Conclusions:This study showed no significant correlation between the inflammatory index levels of middle-aged and elderly male residents around the uranium mine and uranium mining. Age, smoking, BMI and fruit consumption were the influencing factors on the levels of inflammatory indicators of middle-aged and elderly male residents.

Objective:To investigate differential gene expression, enriched biological processes, and pathway differences between residents of a high-background radiation area (HBRA), Yangjiang, and a control area—Enping.Methods:Seven residents were selected from the HBRA (the HBRA group) and seven from the control area (the control group) using the two-stage random sampling method. The cumulative radiation dose for each individual was calculated based on the ambient gamma exposure levels. Peripheral blood samples were collected and analyzed via high-throughput sequencing to identify differentially expressed genes. Subsequent analyses included gene ontology (GO) for biological process (BP), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA).Results:The median ages of the HBRA and control groups had no statistically significant difference ( P = 0.370). The cumulative external doses for the HBRA and control groups were (99.59±20.07) and (33.82±10.61) mSv, respectively. This difference was statistically significant ( t = -5.88, P = 0.001). High-throughput sequencing identified 1 224 differentially expressed genes in the HBRA group, including 32 senescence-related genes, compared to the control group. The result of GO-BP analysis showed that these genes were predominantly enriched in cell signaling, biosynthesis, localization, cell cycle regulation, and cellular stress responses. KEGG analysis revealed significant enrichment in the chemokine and MAPK signaling pathways, as well as in pathways related to the cell cycle, autophagy, and mitophagy. Furthermore, GSEA analysis confirmed that the differentially expressed genes were mainly related to cell cycle regulation and mitochondrial functions. Conclusions:Differentially expressed mRNAs are found in the peripheral blood of residents in the HBRA. These mRNAs are predominantly associated with key biological processes and pathways, including cell cycle regulation, chemokine and MAPK signaling pathways, and mitophagy.

Objective To evaluate the efficacy of case-based learning(CBL)-problem-based learning(PBL)-evidence-based medicine(EBM)integrated teaching method in the standardized training of nephrology resident physicians.Methods Sixty internal medicine trainees who were on a 2-month rotation in the Department of Nephrology between February 1st,2023 and August 31st,2023,were recruited and randomized 1∶1 into the CBL-PBL-EBM group and the CBL group.The scores of the two groups in the theoretical assessment,case analysis,and general skills were compared at the end of the rotation.Results There was no significant difference between experimental group and control group(45.21±3.67 vs 44.02±4.90,P＞0.05).The test scores of test groups were higher than those of control group(42.48±2.35 vs 38.45±3.24,P＜0.05),and the comprehensive scores were higher than those of control group(92.24±1.69 vs 89.21±1.56,P＜0.05).At the same time,the scores of the experimental group in independent learning,literature query ability,critical thinking,and induction and summary ability were al-so significantly better than those of the control group,with statistical significance(P＜0.05).Conclusion The CBL-PBL-EBM teaching method is better than the CBL teaching method,which can effectively achieve the training goals and enhance the overall competence of nephrology trainees.

AIM:To investigate the protective ef-fect of plumbagin(PL)against pulmonary fibrosis(PF)and its possible mechanisms.METHODS:Sixty male C57BL/6 mice were randomly divided into control,bleomycin group(BLM),low dose PL group(1 mg/kg)and high dose PL group(2 mg/kg).The mice PF model was replicated using intratracheal injection of BLM(3 mg/kg),and then PL(1 or 2 mg/kg)was injected intraperitoneally for 3 weeks and the animals were executed.HE and Masson staining were used to observe morphological changes in lung tissue and collagen deposition.The activities or levels of superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA)and hy-droxyproline(HYP)were measured in mouse lung tissue;ELISA for interleukin-6(IL-6)in mouse lung tissue.Immunohistochemical detection of nuclear factor-related factor 2(Nrf2)and reduced nicotin-amide adenine dinucleotide phosphate oxidase 4(NOX4)positive cell expression in mouse lung tis-sue.The expression levels of α-smooth muscle ac-tin(α-SMA),collagen Ⅰ(Col Ⅰ),collagen Ⅲ(Col Ⅲ),IL-6,transforming growth factor-β1(TGF-β1),p-Smad2,Nrf2 and NOX4 were detected by Western blotting.RESULTS:Compared with the BLM group,PL treatment attenuated lung parenchymal and in-terstitial injury and extracellular matrix deposition in mice,reduced HYP content(P＜0.01,P＜0.05),de-creased protein expression of α-SMA,collagen Ⅰand Ⅲ(P＜0.01,P＜0.05),diminished IL-6 secretion(P＜0.01);improved the body's antioxidant capacity(increased SOD and GSH activity and decreased MDA content,P＜0.01,P＜0.05),significantly down-regulated TGF-β1,p-Smad2 and NOX4-positive cells and protein expression(P＜0.01,P＜0.05)and up-regulated Nrf2-positive cells and protein expression(P＜0.01,P＜0.05).CONCLUSION:PL may slow down the PF process by modulating the TGF-β1/Smad2 and Nrf2/NOX4 pathways to attenuate inflammato-ry responses and collagen deposition and improve the body's antioxidant capacity.

Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.

Objective:To investigate the inflammatory indicator levels and influencing factors on middle-aged and elderly male residents at different residential distances from a uranium mine in Guangdong, so as to provide scientific data for the health risk assessment of the residents therein.Methods:With stratified sampling method, two groups of the permanent middle-aged and elderly male residents were randomly sampled within < 10 km and 10-20 km of the uranium mine, along with the basic demographic characteristics and lifestyle information collected through face-to-face questionnaire survey. Both height and weight of the respondents were measured using standard method and their body mass indexes (BMI) were calculated. Through collection of the venous blood, the levels of a wide range of inflammatory indicators were measured, such as C-reactive protein (CRP), complement C3, complement C4, leukocytes, lymphocytes, neutrophils, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and others. Multiple linear regression was used to analyze the influencing factors on the levels of inflammation indicators.Results:A total of 867 middle-aged and elderly male residents were included in this study, including one group of 431 residents within the 10-20 km at an average age of 51.54±5.37, and a second group of 436 residents within <10 km at an average age of 52.05±5.24. The result of multiple linear regression showed a positive correlation of the distance groups with complement C4 level ( β=0.014, 95% CI: 0.001-0.027) and lymphocyte number ( β=0.086, 95% CI: 0.003-0.168) ( t=2.07, 2.04, P<0.05). The ages of middle-aged and elderly male residents around the uranium mine was positively correlated ( t=2.50, P<0.05) with the levels of complement C4 ( β=0.018, 95% CI: 0.004-0.031), and negatively correlated ( t=-3.25, -2.97, P<0.05) with the levels of TNF-α ( β=-63.022, 95% CI: -101.114 to -24.929) and IL-6 ( β=-14.694, 95% CI: -24.396 to -4.992). Smoking was positively correlated ( t=4.29, 4.81, 3.19, P<0.05) with leukocytes number ( β=0.630, 95% CI: 0.341-0.918), lymphocytes number ( β=0.226, 95% CI: 0.134-0.319) and neutrophils number ( β=0.372, 95% CI: 0.143-0.601), and negatively correlated ( t=-2.07, -1.98, P<0.05) with the levels of TNF-α ( β=-43.551, 95% CI: -84.778 to -2.324) and IL-6 ( β=-10.603, 95% CI: -21.103 to -0.102). BMI was positively correlated ( t=8.60, 3.62, 3.18, 4.01, 2.10, P<0.05) with complement C3 level ( β=0.108, 95% CI: 0.084-0.133), complement C4 level ( β=0.026, 95% CI: 0.012-0.039), leukocytes number ( β=0.433, 95% CI: 0.166-0.699), lymphocyte number ( β=0.175, 95% CI: 0.089-0.261), and neutrophil number ( β=0.226, 95% CI: 0.014-0.438). Fruit consumption ( β=0.017, 95% CI: 0.001-0.034) was positively correlated with complement C4 levels ( t=2.10, P<0.05). Conclusions:This study showed no significant correlation between the inflammatory index levels of middle-aged and elderly male residents around the uranium mine and uranium mining. Age, smoking, BMI and fruit consumption were the influencing factors on the levels of inflammatory indicators of middle-aged and elderly male residents.

Objective:To investigate differential gene expression, enriched biological processes, and pathway differences between residents of a high-background radiation area (HBRA), Yangjiang, and a control area—Enping.Methods:Seven residents were selected from the HBRA (the HBRA group) and seven from the control area (the control group) using the two-stage random sampling method. The cumulative radiation dose for each individual was calculated based on the ambient gamma exposure levels. Peripheral blood samples were collected and analyzed via high-throughput sequencing to identify differentially expressed genes. Subsequent analyses included gene ontology (GO) for biological process (BP), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA).Results:The median ages of the HBRA and control groups had no statistically significant difference ( P = 0.370). The cumulative external doses for the HBRA and control groups were (99.59±20.07) and (33.82±10.61) mSv, respectively. This difference was statistically significant ( t = -5.88, P = 0.001). High-throughput sequencing identified 1 224 differentially expressed genes in the HBRA group, including 32 senescence-related genes, compared to the control group. The result of GO-BP analysis showed that these genes were predominantly enriched in cell signaling, biosynthesis, localization, cell cycle regulation, and cellular stress responses. KEGG analysis revealed significant enrichment in the chemokine and MAPK signaling pathways, as well as in pathways related to the cell cycle, autophagy, and mitophagy. Furthermore, GSEA analysis confirmed that the differentially expressed genes were mainly related to cell cycle regulation and mitochondrial functions. Conclusions:Differentially expressed mRNAs are found in the peripheral blood of residents in the HBRA. These mRNAs are predominantly associated with key biological processes and pathways, including cell cycle regulation, chemokine and MAPK signaling pathways, and mitophagy.

Objective To investigate the role of the O-6-methylguanine-DNA methyltransferase (MGMT) gene-3′ untranslated region (UTR) microRNA-associated single nucleotide polymorphism (miRSNP) (rs7896488 G>A) in affecting miR-4297-targeted modulation of MGMT in senescence of lung cells with polymorphic genotypes induced by fractionated low dose ionizing radiation (LDIR). Methods i) MiRSNPs were predicted and screened using bioinformatics, and DNA from two types of lung cells, A549 cells and human bronchial epithelioid cells (HBE cells), was extracted for target gene sequencing. After co-transfection of pGL3c-MGMT-3′UTR-rs7896488 G>A reporter gene recombinant plasmid, pRL-TK Vector with micrON mimic NC #22 or micrON hsa-miR-4297 mimic (set up as the mimic NC group and the miR-4297 mimic group) in these two types of lung cells, dual luciferase reporter gene assay was performed. The relative expression of MGMT mRNA was detected by real-time fluorescence quantitative polymerase chain reaction, and the relative expression of MGMT protein was detected by Western blotting. ii) These two types of lung cells were randomly divided into the control group and irradiation group, which received either 0 or 100 mGy X-rays irradiation seven times. After irradiation, the cells were transfected with either micrON mimic NC #22 or micrON hsa-miR-4297 mimic, resulting in mimic NC + control group, miR-4297 mimic + control group, mimic NC + irradiation group, and miR-4297 mimic + irradiation group. Cells were collected for senescence-associated-β-galactosidase (SA-β-Gal) staining, and the relative expression of matrix metalloproteinase-9 (MMP-9) and chemokine (C-X-C motif) ligand-1 (CXCL-1) proteins was detected via Western blotting. Results i) The rs7896488 G>A was the miRSNP located in the conserved binding region targeted by miR-4297 in the MGMT gene 3′UTR. A549 cells were the rs7896488 GG wild-type homozygous genotype, while HBE cells were the rs7896488 GA heterozygous mutant genotype. In the miR-4297 mimic group, A549 and HBE cells carrying the rs7896488 G allele showed significantly lower dual-luciferase activity compared with that in the mimic NC group (both P<0.01). However, there was no significant difference in dual-luciferase activity between the two groups in both A549 and HBE cells carrying the rs7896488 A allele (both P>0.05). The relative expression levels of MGMT mRNA and MGMT protein of A549 cells in the miR-4297 mimic group were lower than those in the mimic NC group (both P<0.05). However, there was no significant difference in MGMT mRNA and MGMT protein of HBE cells between these two groups (both P>0.05). ii) The relative activity of SA-β-Gal and the relative expression of MMP-9 and CXCL-1 proteins of A549 cells in the miR-4297 mimic+irradiation group were higher than those in the mimic NC + control group, the miR-4297 mimic + control group, and the mimic NC + irradiation group (all P<0.05). The relative activity of SA-β-Gal and the relative expression of MMP-9 and CXCL-1 proteins of HBE cells in the miR-4297 mimic + irradiation group were higher than those in the mimic NC + control group and the miR-4297 mimic + control group (all P<0.05), while there was no significant difference compared with those in the mimic NC + irradiation group (all P>0.05). Conclusion MGMT-3′UTR-miRSNP rs7896488 G>A plays a role in LDIR-induced senescence of lung cells with different polymorphic genotypes by affecting miR-4297-targeted regulation of MGMT.