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Objective To explore the acute effects of NO2 on children's respiratory hospitalization risk in Foshan City. Methods The daily average concentrations of six air pollutants such as NO2 and fine particulate matter, and meteorological data including average temperature and relative humidity in Foshan were collected from 2016 to 2019. Data on the daily number of children newly hospitalized for respiratory diseases (ECRH) in Foshan Women and Children Hospital were retrieved. Time series analysis was used to quantitatively evaluate the effect of daily NO2 concentration on the hospitalization risk of children with respiratory diseases. Results From 2016 to 2019, the average ECRH in the hospital was 10. The daily average concentrations of air pollutants NO2, PM2.5, PM10, and SO2 were 42.0 μg/m3, 35.3 μg/m3, 58.1 μg/m3, and 11.4 μg/m3, respectively. The air pressure, daily average temperature and relative humidity of atmosphere were 1008.4 Pa, 23.7℃ and 73.3%, respectively. ECRH was significantly correlated with the daily average concentration of NO2 (r=0.079, P3 increase of NO2 concentration in the single pollutant model, the excess risk of ECHR in the hospital increased by 1.22% (95% CI: 0.06%, 2.40%) and 1.37% (95% CI: 0.23%, 2.53%) in lag0 and Lag1 day, respectively. The strongest effect appeared in lag0:7 with the excess risk increasing by 1.70% (95% CI:0.12%, 3.31%). In the NO2 + SO2 + CO + O3_8h + PM2.5 and NO2 + SO2 + CO + O3_8h + PM10 multi-pollutant models, significance correlation still existed between the daily average NO2 concentration and ECHR in lag0, lag1 and lag0:1 to lag0:7. The strongest effect appeared in lag0:1, and the excess risks were 4.06% (95% CI: 1.83%, 6.34%) and 3.95% (95% CI: 1.85%, 6.09%), respectively. Dose-response relationship analysis showed a linear relationship between the daily average NO2 concentration and ECHR, and the excess risk of new hospitalization gradually increased with the increase of daily average NO2 concentration. Conclusion There was a significant correlation between NO2 concentration and hospitalization risk of children with respiratory diseases in Foshan City, which suggests that the government should further strengthen the prevention and control of air pollution.
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Objective: To investigate the postoperative prognostic factors of non-metastatic colorectal cancer (non-mCRC), and construct a prognostic prediction model. Methods: A total of 846 patients with colorectal cancer who were admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from July 1, 2014 to December 31, 2016 were included in the study. There were 314 patients in the metastatic colorectal cancer (mCRC) group and 532 patients in the non-mCRC group. The data of clinical characteristics, preoperative blood routine and common serum tumor markers for CRC tests were collected retrospectively. The disease-free survival time (DFS) data of patients in non-mCRC group were obtained by follow-up. Univariate and multivariate Cox regression analyses were used to clarify the independent risk factors of DFS, and then these factors were included to construct a nomogram prediction model. The concordance index (C index), receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the performance of the model. Results: Platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 242 (CA242) in the mCRC group were higher than those of the non-mCRC group, while the lymphocyte/monocyte ratio (LMR) was lower than that of the non-mCRC group (P<0.05). ROC analysis showed that the area under curve (AUC) of CEA, CA19-9, CA242, NLR, LMR and PLR for the diagnosis of mCRC were 0.775, 0.716, 0.712, 0.607, 0.591 and 0.556, respectively. Multivariate Cox regression analysis demonstrated that age, perineural invasion, pN stage and preoperative CA242 level were independent risk factors for DFS of non-mCRC patients (P<0.05). Based on this, a nomogram prediction model predicting 3 years of DFS for non-mCRC patients was constructed, its C index and AUC for non-CRC prognostic prediction were 0.710 and 0.733, respectively, higher than 0.696 and 0.701 of AJCC 7th edition TNM staging system. The calibration curve of nomogram showed that the predicted DFS rate was consistent with the actual DFS rate. Conclusions: Age, perineural invasion, pN stage and preoperative CA242 level are independent risk factors for 3-year DFS of non-mCRC patients. The nomogram prediction model constructed based on these four indictors has a good predictive performance and may provide prognosis evaluation reference for the patients with non-mCRC.
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Humans , CA-19-9 Antigen , Colonic Neoplasms , Colorectal Neoplasms , Lymphocytes , Prognosis , Retrospective StudiesABSTRACT
Aim To investigate the mechanism of the mediation of high mobility group protein BI (HMGB1) and Toll like receptor 4 (TLR4) in the proliferation and extracellular matrix deposition of glomerular mesangial cells in lupus nephritis. Methods Immunohistochemistry and immunocytochemistry were employed to detect the TLR4 expression levels in the LN clinical specimens and MRL/lpr mice. Western blot was used to detect the TLR4 and Myd88 expression levels in human mesangial cells stimulated by recombinant HMGB1. Cell counting kit-8, Western blot and ELISA were employed to detect the proliferation and FN expression levels in HMCs stimulated by the exchange plasma of LN patients. Results Immunohistochemistry and immunocytochemistry results showed that compared with control groups,the expression levels of TLR4 in glomeruli cells of LN patients and MRL/lpr mice were up-regulated. Western blot showed that compared with control groups, the expression levels of TLR4 and Myd88 increased in HMCs stimulated by recombinant HMGB1. While the inhibition of HMGB1 and TLR4 both improved the proliferation, FN synthesis and FN secretion of HMCs induced by the exchange plasma of LN patients (both P < 0. 05). Conclusion HMGB1 may participate in the pathogenesis of LN by activating TLR4 to mediate the proliferation and extracellular matrix deposition of mesangial cells.
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Objective: To study the chemical constituents from the leaves of Adinandra nitida. Methods: The chemical constituents of the plant were isolated and purified by column chromatography and their structures were elucidated on the basis of physicochemical properties and spectral data. Results: Eleven triterpenoids, two diterpenoids, and two steroids were obtained and determined to be ursolic acid (1), 18-hydroxyursolic acid (2), 2α,3α-dihydroxyursolic acid (3), 3α,19α-dihydroxyursolic acid (4), euscaphic acid (5), 3β,19α,23-trihydroxyursolic acid (6), 2α,3α-dihydroxyursolic acid-28-O-β-D-glucopyranoside (7), kajiichigaside F1 (8), oleanolic acid (9), arjunetin (10), betulinic acid (11), cassipourol (12), α-tocopherol (13), daucosterol (14), and β-sitosterol (15). Conclusion: Compounds 1-4, 6, 7, 9, and 11-13 are obtained from the leaves of A. nitida for the first time.
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<p><b>OBJECTIVE</b>To explore the possible mechanism of lipid deposition induced by interferon-gamma (IFN-gamma).</p><p><b>METHODS</b>The mouse mesangial cells (MMC) were randomly divided into control group, stimulation group, stimulation + control vector group (sh-HMGB1) and stimulation+ specific sh-vector group (sh-SREBP-1). RT-PCR was used to detect the expression of HMGB1, SREBP-1 and fatty acid synthetase (FAS) mRNA; the protein expression was determined by Western blot.</p><p><b>RESULTS</b>The Oil Red O staining revealed that the mouse mesangial cells showed significant lipid droplet in IFN-gamma group. IFN-gamma up-regulated the expression of HMGB1, SREBP-1, FAS mRNA and protein time-dependently; Transfection of MMC with HMGB1 siRNA resulted in the suppression of SREBP-1, FAS protein levels induced by IFN-gamma, following with decrease of lipid deposition. Stimulation with HMGB1 markedly induced expression of SREBP-1, FAS expression and peaked at 8 h, decreased at 12 h compared with that at 8 h. Sh-SREBP-1 decreased the lipid deposition induced by HMGB1 in MMC.</p><p><b>CONCLUSION</b>IFN-gamma might induce lipid deposition in mouse mesangial cells partly by up-regulating the expression of HMGB1/SREBP-1/FAS.</p>
Subject(s)
Animals , Male , Mice , Cells, Cultured , Fatty Acid Synthases , Metabolism , HMGB1 Protein , Metabolism , Interferon-gamma , Pharmacology , Kidney Tubules , Cell Biology , Lipid Metabolism , Mesangial Cells , Metabolism , Sterol Regulatory Element Binding Protein 1 , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the expressions of B lymphocyte activating factor (BAFF) in the serum and peripheral blood B cells (PBBCs) of BXSB lupus nephritis mice, and to investigate the efficacy of Langchuangping Granule (LG).</p><p><b>METHODS</b>Eighteen 11-week-old male BXSB lupus mice were randomly divided into three groups, i.e., the lupus control group, the hormone treatment group, and the LG treatment group, 6 in each group. Besides, another 6 C57BL/6 male mice were recruited as the normal control group. The mice were given with normal sodium (10 mL/d), methylprednisolone (at the daily dose of 5 mg/kg), LG (at the daily dose of 4 g/kg), and the normal saline (10 mL/d) respectively by gastrogavage for 4 weeks. The urine protein, ds-DNA, and body weight were determined. The serum soluble BAFF (sBAFF), the expressions and changes of BAFF-mRNA in the PBBCs were detected using ELISA and RT-PCR respectively. The activity index (AI) and 24 h urine albumin excretion quantitation of renal pathological activities were observed. The correlation between ds-DNA and sBAFF were analyzed.</p><p><b>RESULTS</b>The level of sBAFF in serum, the BAFF mRNA level in PBBCs, 24 h urinary albumin excretion, and serum ds-DNA content increased more obviously in lupus mice than in the normal mice. After being treated by methylprednisolone or LG, the sBAFF and BAFF mRNA expressions decreased more obviously than before treatment, showing statistical difference (P<0.05). But there was no statistical difference in the sBAFF level or the BAFF mRNA expression (P>0.05). There was positive correlation between sBAFF and AI (r=0.8098, P<0.01), 24 h urinary albumin excretion (r=0.8220, P<0.01), and ds-DNA (r=0.8535, P<0.01).</p><p><b>CONCLUSIONS</b>BAFF plays an important role in the occurrence and development of lupus nephritis. It can be used in monitoring the disease progress and predicting its recurrence. It is one of ideal targets for treating lupus nephritis. LG could attenuate the renal injury via suppressing BAFF level. It is worth further clinical application.</p>
Subject(s)
Animals , Male , Mice , B-Cell Activation Factor Receptor , Metabolism , B-Lymphocytes , Metabolism , Disease Models, Animal , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Lupus Nephritis , Allergy and Immunology , Metabolism , Mice, Inbred C57BL , Phytotherapy , RNA, Messenger , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To study whether Langchuangping granule (LG) could exert its renal protection by down-regulating monocyte chemoattractant protein-1 (MCP-1) via suppressing nuclear factor kappa B (NF-kappaB) signaling pathway in BXSB lupus nephritis (LN) mice. Methods Eighteen male 11-week-old BXSB LN mice were randomly divided into three groups, i.e., the model group, the hormone group, and the Chinese medicine group, 6 in each. They were administered by gastrogavage with normal saline, methylprednisolone, and LG, respectively. Another six C57BL/6 male mice of the same age was taken as the normal control group, which was administered with normal saline by gastrogavage. All mice were treated once daily, for 4 successive weeks. The 24-h urine protein was determined. The mRNA and protein expressions of MCP-1 in the renal tissue were detected using RT-PCR and Western blot. The expression of NF-kappaB p65 in the renal tissue was detected using immunohistochemical assay. Activity index (AI) of the renal tissue was counted using PAS stain. The content of ds-DNA antibody was detected using ELISA. The correlations of the aforesaid indices were analyzed.</p><p><b>RESULTS</b>The 24-h urine protein level, serum ds-DNA antibody content, protein and mRNA expressions of MCP-1, NF-kappaB p65 expression level, and AI count were obviously higher in the model group than in the normal control group (P < 0.01). The aforesaid indices all obviously decreased after medication in the Chinese medicine group and the hormone group (P < 0.05). MCP-1 protein expression level was positively correlated with MCP-1 mRNA, NF-kappaB p65, AI, 24-h urine protein, and ds-DNA antibody of all LN mice (r= 0.984, 0.936, 0.887, 0.698, 0.679, all P < 0.01).</p><p><b>CONCLUSIONS</b>LG possibly played renal protection by down-regulating NF-kappaB-mediated MCP-1 expression levels. MCP-1 played important roles in the occurrence and development of LN, being one of ideal targets for LN treatment.</p>
Subject(s)
Animals , Male , Mice , Chemokine CCL2 , Metabolism , Disease Models, Animal , Down-Regulation , Drugs, Chinese Herbal , Pharmacology , Kidney , Metabolism , Lupus Nephritis , Metabolism , Mice, Inbred C57BL , NF-kappa B , Metabolism , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of high fat diet on the expression of sterol regulatory element binding protein-1 (SREBP-1), transforming growth factor-beta1 (TGF-beta1) and alpha-smooth muscle actin (alpha-SMA) in renal tubular cells and extracellular matrix accumulation in Wistar rats.</p><p><b>METHODS</b>The Wistar rats were treated with high fat diet for 12 weeks and renal lipid deposit was detected by the method of Oil Red O staining. The immunohistochemistry and Western blot were used to investigate the expression of SREBP-1, TGF-beta1, alpha-SMA and fibronectin (FN) protein. The expression of SREBP-1 mRNA was determined with in situ hybridization. Masson staining was for the detection of extracellular matrix (ECM) accumulation.</p><p><b>RESULTS</b>The weight of rats raised by high fat diet increased, in company with the high serum glucose, serum triglyceride and serum insulin. The Oil Red O staining revealed that the renal proximal tubular epithelial cells showed significant lipid droplet in high fat diet rats. SREBP-1 protein and mRNA were located in the renal tubular cells and the expressions of high fat diet rats were higher than those of normal control rats. They were respectively 1.88 times and 1.85 times than those of normal control group. TGF-beta1 and alpha-SMA protein were also located in renal tubular cells and high fat diet up-regulated the expression of them. ECM accumulation was detected with Masson staining and the result showed that high fat diet treatment increased interstitial ECM product and FN protein was found high expression.</p><p><b>CONCLUSION</b>High fat diet may induce lipid droplet deposit in renal tubular cells by up-regulation of the expression of SREBP-1, which causes ECM accumulation by increasing the expression of TGF-beta1 and alpha-SMA.</p>
Subject(s)
Animals , Male , Rats , Actins , Metabolism , Diet, High-Fat , Extracellular Matrix , Metabolism , Kidney Tubules , Cell Biology , Metabolism , Rats, Wistar , Sterol Regulatory Element Binding Protein 1 , Metabolism , Transforming Growth Factor beta1 , MetabolismABSTRACT
<p><b>AIM</b>To investigate the effect of puerarin on expressions of MMP-2 and TIMP-2 in the kidney of diabetic rats.</p><p><b>METHODS</b>Uninephrectomized male Wistar rats were used to induce diabetes by intraperitoneal injection of streptozocin (65 mg x kg(-1)). Puerarin was given daily by intraperitoneal injection from the third day of induction of diabetes for 16 weeks. Using in situ hybridization and immunohistochemistry to detect MMP-2, TIMP-2 mRNA expressions and MMP-2, TIMP-2, collagen IV and Laminin expressions in diabetic kidneys with image analysis system, Flow cytometry was used to detect the expressions of TGFbeta1, MMP-2 and TIMP-2.</p><p><b>RESULTS</b>Compared with those in kidneys of control group, expressions of MMP-2 mRNA and proteins were lower, while the expressions of both TGFbeta1 and TIMP-2 were higher in the diabetic kidney (P < 0.05). The level of MMP-2 expression was advanced, while expression of TIMP-2 was reduced by puerarin treatment (P < 0.05).</p><p><b>CONCLUSION</b>Puerarin showed some renal protective effect on diabetic nephropathy, partly through inhibition of excessive deposition of glomeruli extracellular matrix by up-regulating MMP-2 and down-regulating TIMP-2 expressions besides reducing the blood glucose.</p>