Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

Social capital, as a significant social factor influencing human life, plays a crucial role in improving the quality of life of the aged. Different dimensions of social capital have varying mechanisms and effects on the quality of life of the aged. Therefore, this article reviews both cognitive and structural social capital, aiming to provide a basis for improving the quality of life of the aged in China.

Objective:To understand the dilemma of active management in young and middle-aged postoperative patients with lumbar disc herniation, in order to provide reference for the formulation of active intervention program of self-health management meeting the needs of patients.Methods:Using the phenomenological research method, a total of 16 middle-aged and young patients with lumbar disc herniation were selected for semi-structured in-depth interviews, and the themes were analyzed and extracted by Colaizzi 7-step analysis method.Results:Three themes and nine sub-themes were extracted namely, inadequate disease response capacity and response resources (lack of disease symptom management capacity, limited access to disease management information, difficult use of disease management information, difficulty in maintaining positive self-management for a long time (forced to stop behavior change due to stress, lack of motivation to achieve good behavior change, doubts about the effectiveness of self-management) and multi-dimensional negative emotions (contrast between maintaining independence and dependence on others, fear of being misunderstood, fear of relapse) .Conclusions:Medical staff should provide comprehensive health information services for young and middle-aged postoperative patients with lumbar disc herniation, improve the out-of-hospital follow-up mechanism with the help of information technology, further improve family and social support strategies, reduce the difficulties faced in the process of active management and achieve long-term active disease management.

Objective To analyze the epidemiological characteristics of new elderly malignant tumor cases in Tongren City from 2018 to 2022, so as to provide a theoretical basis for the prevention and control of elderly malignant tumor in this area. Methods A retrospective analysis of the epidemiological characteristics of cases aged 60 and above who were first diagnosed with malignant tumors by pathology in our hospital from 2018 to 2022 was conducted based on the International Classification of Diseases (ICD-10). Results The incidence rate of elderly malignant tumors in Tongren City increased from 123.83/100 000 in 2018 to 126.14/100 000 in 2022, and the incidence rate showed a trend of first rising and then declining. The top five tumors in incidence rate are lung cancer, rectal cancer, liver cancer, stomach cancer and cervical cancer. The tumor order has changed over the years except lung cancer, which was the first. Lung cancer was the main high incidence tumor among the elderly of all ages. With the increase of age, the number of bladder cancer patients increases significantly, and the number of colon cancer patients also shows an upward trend. The prevalence rate of lung cancer（χ²=16.032，P=0.014) , liver cancer（χ²=8.099，P=0.030) , bladder cancer（χ²=11.274 , P=0.018) , and gastric cancer（χ²=19.387 , P=0.011) in elderly people of different sexes was generally higher in men than in women, and the difference was statistically significant (P<0.05). Conclusion Lung cancer , rectal cancer and liver cancer, as the malignant tumors with high case composition and rapid increase in the elderly, can be the focus of early screening and prevention of malignant tumors in the elderly in Tongren City, and men should pay more attention.

ObjectiveTo study the mechanism of Mahuang Xixin Fuzitang （MXFT） against migraine. MethodTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， SiwssTargetPrediction and other databases were used to screen the active components and action targets of MXFT as well as migraine-related targets. The potential protein-protein interaction （PPI） network diagram was plotted for the intersection targets of MXFT and migraine using STRING 11.5. Metascape was used for Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis of potential intersection targets. The component-target-pathway network of MXFT was constructed by Cytoscape 3.7.1 to screen core targets with high degree value. Finally， the binding strength between core target and its mapping components was verified by molecular docking， and the core targets with desirable docking results were verified by animal experiments in vivo. Forty eight SD rats were selected， and except the blank group， the other rats were subcutaneously injected with nitroglycerin to prepare the migraine rat model. The modeled rats were randomly divided into model group， positive drug group and MXFT high-， medium- and low-dose groups. The positive drug group was given zolmitriptan tablets， and the MXFT high-， medium- and low-dose groups were given high， medium and low doses of MXFT， respectively. The changes of behavior and pain threshold of rats in each group were observed every other day after modeling. The levels of calcitonin gene-related peptide （CGRP）， extracellular signal-regulated kinase 2 （ERK2） and c-fos proto-oncogene （FOS） protein in plasma were detected by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemical technique and Western blot were employed to determine the levels of extracellular signal-regulated kinase 1/2 （ERK1/2， also known as MAPK1/3） and protein kinase B 1 （Akt1）， protein kinase C α （PRKCA） in trigeminal nerve of SD rats. ResultThe network pharmacology showed that the core targets of MXFT in the treatment of migraine were MAPK1， MAPK3， Akt1， PRKCA， etc.， mainly involving neuroactive ligand-receptor interaction signaling pathway， calcium signaling pathway， MAPK signaling pathway， etc. The molecular docking demonstrated that MAPK1， MAPK3， Akt1， PRKCA， PRKCB and PRKCG had good binding ability with their mapping components. The animal experiments indicated that compared with the conditions in the blank group， the number of head scratching in the model group was increased （P<0.01）， and the pain threshold was decreased （P<0.01）. Compared with the conditions in the model group， the number of head scratching in each administration group was reduced （P<0.01）， and the pain threshold was increased （P<0.01）. In addition， the levels of CGRP， ERK2 and FOS proteins in plasma， and Akt1， ERK1/2 and PRKCA proteins in trigeminal ganglion of the model group were higher than those of the blank group （P<0.05， P<0.01）. The levels of CGRP， ERK2 and FOS proteins in plasma and Akt1， ERK1/2 and PRKCA proteins in trigeminal ganglion of each administration group were lower than those of the model group （P<0.05， P<0.01）. ConclusionMXFT had multi-component， multi-target and multi-pathway characteristics in the treatment of migraine， and the mechanism might be related to inhibiting vasodilation， reducing the release of inflammatory factors and inhibiting neuronal hyperactivity.

In order to study genetic variation diversity of porcine circovirus type 2 (PCV2) strains in Shanxi,the genomic sequences of nine PCV2 strains including SXQX,SXCZ,SXTY2,SXJC,SXJX,SXLL,SXPY,SXPG and SXXY recently isolated from some areas of Shanxi from 2013 to 2016,was cloned,sequenced and received by GenBank.The amplified PCV2 genomic sequences,ORF2 sequences and Cap protein amino acid of these nine strains were analysed and compared with those of published 28 PCV2 strains by DNAStar,drawing phylogenetic tree.The results showed that the genomic sequences of SXJX,SXJC and SXXY PCV2 strains were 1 768 bp,and the others were 1 767 bp,which accounted for 33％ and 67％,respectively.The homologies of nucleotide sequences of the nine strains were 94.7％-99.8％,the homologies of nucleotide sequences of the nine strains with the 28 isolates from different regions of the world PCV strain were 93.9％-99.9％,and the homologies of nucleotide sequences of the nine strains with the domestic vaccine strains were 95.1％-99.8％.The phylogenetic analysed that SXJX,SXJC and SXXY belonged to genotype PCV-2D,SXLL,SXPY and SXCZ belonged to genotype PCV-1C,and SXTY14,SXPG and SXQX belonged to genotype PCV-1A/1B.Thus it proved that the epidemic strain of PCV2 was mainly PCV-2b in Shanxi.The homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains were 90.0％-100.0％ and 87.1 ％-100.0％ respectively,the homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains with the 28 isolates from different regions of the world PCV strain were 87.6％-100.0％ and 84.1％-100.0％ respectively,and the homologies of ORF2 nucleotide sequences and Cap amino acid of the nine strains with the domestic vaccine strains were 91.0％-100.0％ and 89.3％-100.0％ respectively.The Cap amino acids of SXQX,SXJX,SXTY14,SXPG,SXJC and SXXY PCV2 were 233,ORF2 of SXQX,SXTY14 and SXPG located at 1 033-1 734 bp,ORF2 of SXXY,SXJX and SXJC located at 1 033-1 734 bp,and the Cap amino acids of SXCZ,SXLL and SXPY PCV2 were 234,ORF2 of them located at 1 030-1 734 bp,in addition,the positions of 1 030-1 734 bp were more three bases TCA than other ORF2 genome sequence of 1 767 bp,resulting in increasing a K (Lys) of amino acid sequencein at the 234 position.Also Cap protein of 9 PCV2 strains showed more amino acid variation in addition to the only high-ly conserved glycosylation sites (NYS) (pp.143-145 amino acid).It provided theoretical basis for the PCV2 immune prevention of research in Shanxi,and the data of basic theory of molecular pathogenesis of PCV2.

ObjectiveTo investigate the protective effect of paraoxonase 1 (PON1) gene against liver oxidative stress injury in mice due to dichlorvos poisoning.Methods Experiment 1: 12 male Balb/c mice were randomly divided into three groups, with 4 mice in each group: control group, green fluorescent protein lentivirus control group (Lv-GFP group), and recombinant PON1 lentivirus group (Lv-PON1 group). 2×107 TU of Lv-GFP or Lv-PON1 was transfected via tail vein, while normal saline was given to those in control group. Blood was collected on 0, 1, 3, 5, 7, 9 days via fundus venous plexus for the assay of serum PON1 activity. PON1 mRNA and protein expression levels were respectively determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot on the 3rd post-lentivirus transfection day. Experiment 2: according to the random number table method, another 96 male Balb/c mice were divided into four groups of 24 mice in each control group, dichlorvos group, Lv-GFP intervention group, and Lv-PON1 intervention group. Lv-GFP or Lv-PON1 was transfected via tail vein followed by intraperitoneal injection of dichlorvos 9 mg/kg, while those in control group were given normal saline. Six mice in each group were sacrificed respectively at 6, 12, 24, 48 hours, and liver tissue was collected. PON1 mRNA and nuclear factor E2-related factor 2 (Nrf2) mRNA expression levels were determined by RT-PCR, and PON1 protein level was determined by Western Blot. The content of malondialdehyde (MDA) and glutathione (GSH) in the liver tissue were determined by chemical colorimetry. The activity of superoxide dismutase (SOD) and catalase (CAT) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA).Results Experiment 1: after Lv-PON1 was transfected to normal mice, PON1 activity in serum gradually increased and maintained a high level on 3rd day, while that of the control group and Lv-GFP group showed a normal low level. On the 3rd post-lentivirus transfection day, PON1 mRNA and PON1 protein expressions in liver were significantly higher than those of control group and Lv-GFP group. Experiment 2: compared with control group, the mice in dichlorvos group showed significant decreases in PON1 mRNA, PON1 protein, Nrf2 mRNA as well as GSH, SOD, CAT levels at 6 hours [PON1 mRNA (gray value):0.237±0.075 vs. 0.674±0.011, PON1 protein (gray value): 0.602±0.086 vs. 0.998±0.124, Nrf2 mRNA (gray value): 0.089±0.012 vs. 0.126±0.010, GSH (mg/g): 3.84±0.33 vs. 5.52±0.40, SOD (μg/g): 0.383±0.040 vs. 0.564±0.052, CAT (ng/g): 7.32±1.28 vs. 12.46±1.54, allP< 0.05], and remarkable increase in MDA content (nmol/g: 7.78±0.41 vs. 2.34±0.25,P< 0.05). With the extension of time, PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels gradually increased, MDA content gradually decreased, Nrf2 mRNA expression level had risen to the level of control group at 24 hours (0.133±0.019 vs. 0.126±0.009,P> 0.05), and it was higher than that of the control group at 48 hours (0.206±0.028 vs. 0.124±0.010,P< 0.05). Compared with that of the dichlorvos group, Lv-PON1 intervention group showed a significant increase in PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels [PON1 mRNA (gray value): 0.726±0.021 vs. 0.237±0.075, PON1 protein (gray value): 0.739±0.050 vs. 0.602±0.086, Nrf2 mRNA (gray value): 0.158±0.007 vs. 0.089±0.012, GSH (mg/g): 4.30±0.22 vs. 3.84±0.33, SOD (μg/g): 0.454±0.062 vs. 0.383±0.040, CAT (ng/g): 8.98±1.02 vs. 7.32±1.28, allP< 0.05], and a decrease in MDA content (nmol/g: 6.56±0.44 vs. 7.78±0.41,P< 0.05).Conclusion Regulation of PON1 gene can reduce MDA content, enhance SOD and CAT activities, increase GSH content, and it may also up-regulate Nrf2 mRNA expression to play a protective effect against oxidative stress of liver injury induced by dichlorvos poisoning.

OBJECTIVETo measure the levels of ghrelin-induced expression or activation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and

NAD(P)Hquinone oxidoreductase 1 (NQO1) in the PQ-injured lungs of mice and to evaluate the protective effect of ghrelin against paraquat (PQ)-induced acute lung injury in mice.

METHODSAccording to the random number table method, 50 ICR mice of clean grade were assigned to 5 groups: normal control group (n = 10), PQ group (n = 10), and ghrelin intervention groups (n = 30). For PQ group, mice were injected with a single dose of PQ (20 mg/kg, i.p.); for ghrelin intervention groups, mice were injected with a single dose of PQ (20 mg/kg, i.p.), and then ghrelin was injected at three concentrations (16.58, 33.15, and 49.73 µg/kg). Lung tissues were collected and proceeded to the following studies. HE staining was used for histopathological examination under a light microscope, and the changes in nuclear expression of Nrf2 were evaluated by Western blot. The activities of HO-1 and NQO1 were measured by ELISA. Malondialdehyde (MDA) content and MPO activity were measured by colorimetry. Another 40 mice were divided into PQ group (n = 10) and 16.58, 33.15, and 49.73 µg/kg ghrelin intervention groups (n = 10 for each); mortality and clinical manifestations were recorded within 72 h.

RESULTSCompared with the normal control group, the PQ group showed significant increases in nuclear protein level of Nrf2, content of MDA, and activities of HO-1, NQO1, and MPO (P < 0.05 for all). Compared with the PQ group, ghrelin treatment significantly increased the expression of Nrf2 and activities of HO-1 and NQO1 and significantly reduced the content of MDA and activity of MPO (P < 0.01 for all). Histopathological studies indicated that ghrelin showed an antioxidant property that reduced the histological changes induced by PQ in the lungs. The ghrelin intervention groups had a significantly lower mortality than the PQ group, and there was a significant difference between the high-dose ghrelin intervention group and PQ group (P < 0.05).

CONCLUSIONGhrelin can up-regulate nuclear expression of Nrf2, increase the activities of HO-1 and NQO1, and reduce the activity of MPO and content of MDA, thus protecting PQ-exposed mice from acute lung injury.

Acute Lung Injury ; chemically induced ; metabolism ; Animals ; Ghrelin ; pharmacology ; Heme Oxygenase-1 ; metabolism ; Lung ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Membrane Proteins ; metabolism ; Mice ; Mice, Inbred ICR ; NAD(P)H Dehydrogenase (Quinone) ; metabolism ; NF-E2-Related Factor 2 ; metabolism ; Oxidative Stress ; Paraquat ; poisoning ; Peroxidase ; metabolism