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AIM:Using bioinformatics analysis and experiment validation to explore the differential expres-sion genes related to abnormal lipid metabolism in hepatocellular carcinoma(HCC)and the molecular mechanism of pachymaran affecting pyroptosis through squalene epoxidase(SQLE)/nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)/gasdermin D(GSDMD)signaling pathway.METHODS:(1)The GEO,GSEA,DAVID,STRING and GEPIA databases were employed to screen abnormal lipid metabolism-related differentially expressed genes in HCC.(2)The tumor tissues from HCC patients(n=9)were collected to verify the differential expression of SQLE.(3)The inhibitory effect of pachymaran on the viability of human HCC cell line HepG2 was measured by CCK-8 assay.(4)The HepG2 cells were divided into control group and pachymaran(800 mg/L)group.The cell migration was analyzed by wound-healing assay,and RT-qPCR was used to measure SQLE mRNA expression.(5)The HepG2 cells with overexpres-sion of SQLE(OE-SQLE)were divided into 5 groups as follows:control group,overexpression negative control(OE-NC)group,OE-SQLE group,OE-NC+pachymaran group,and OE-SQLE+pachymaran group.The mRNA and protein expres-sion levels of SQLE and pyroptosis-related factors were determined by RT-qPCR and Western blot.Colorimetric method and ELISA were used to measure lactate dehydrogenase(LDH),interleukin-1β(IL-1β)and IL-18 levels.The necrosis of HepG2 cells was analyzed by flow cytometry.RESULTS:The SQLE gene was screened through bioinformatics analysis,and its mRNA expression was significantly increased in tumor tissues from HCC patients(P<0.01).In cell experiments,treatment with 800 mg/L pachymaran for 48 h had a significant inhibitory effect on HepG2 cell viability,and the expres-sion of SQLE mRNA was reduced(P<0.01).After overexpression of SQLE,the mRNA and protein levels of pyroptosis-re-lated factors,necrotic rate,and LDH,IL-1β and IL-18 levels were significantly decreased(P<0.05).After treatment with pachymaran,the above indicators were significantly increased(P<0.05).CONCLUSION:The SQLE is abnormal-ly highly expressed in HCC,and pachymaran can affect the growth of HCC cells by activating the NLRP3/GSDMD pyropto-sis pathway through SQLE.
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The key pathogenesis of coronary heart disease (CHD) is spleen deficiency and phlegm stasis, and dysfunctional high-density lipoprotein (dys-HDL) may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein (HDL), it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL; and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways, namely, mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells, thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency, and spleen deficiency makes foundation for the production of dys-HDL; dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen, resolving phlegm, and dispelling stasis, is proposed as an important principle in the treatment of CHD by traditional Chinese medicine, which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL, thus revealing the scientific connotation of this method, and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.
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ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 (Th17)/regulatory T cell (Treg) and Notch1 signaling pathway in mice with autoimmune thyroiditis (AIT). MethodA total of 60 8-week-old NOD.H-2h4 mice were randomly divided into the normal group, model group, western medicine group (selenium yeast tablet, 32.5 mg·kg-1), and low-dose (4.78 g·kg-1·d-1), middle-dose (9.56 g·kg-1·d-1), and high-dose (19 g·kg-1·d-1) Buzhong Yiqitang groups, with 10 mice in each group. The normal group was fed with distilled water, and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously, the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies (TGAb), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroid hormone (FT4) were detected by enzyme-linked immunosorbent assay (ELISA), and thyroid tissue changes were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt (RORγt), interleukin (IL)-17, forkhead box P3 (FoxP3), IL-10, Notch1, and hair division-related enhancer 1 (Hes1) in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultCompared with the normal group, the thyroid structure of the model group was severely damaged, and lymphocytes were infiltrated obviously. The levels of serum TGAb, FT3, and FT4 contents were significantly increased, and TSH content was significantly decreased (P<0.01). The mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were significantly increased, while those of FoxP3 and IL10 were significantly decreased in the model group (P<0.01). Compared with the model group, thyroid structural damage and lymphocyte infiltration were improved in the treatment groups, and serum TGAb, FT3, and FT4 contents were significantly decreased. TSH content was increased, and mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees (P<0.05, P<0.01), and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice, and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.
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ObjectiveTo explore the effect of Banxia Xiexintang (BXT) on the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase-1) pyroptosis pathway and its downstream factors in rats with ulcerative colitis (UC), and to explain the mechanism of BXT in the treatment of UC. MethodSD rats were randomly divided into normal control group, model group, low- and high-dose BXT groups (6.3, 12.6 g·kg-1·d-1), and salazosulfapyridine (SASP) group (0.42 g·kg-1·d-1), with 7 rats in each group. The UC model was induced by intragastric administration of 2.5% dextran sodium sulfate (DSS) solution for 10 days, followed by drug intervention for 7 days. The general state of rats was observed during the experiment, and the disease activity index (DAI) score was calculated during the administration period. At the end of the experiment, colonic tissues were collected for hematoxylin-eosin (HE) staining to observe the pathological changes and the curative effect of BXT. Real-time fluorescence-based quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA transcriptional levels of NLRP3, Caspase-1, gasdermin D (GSDMD), and interleukin (IL)-1β in colonic tissues. Western blot was used to detect the protein expression of NLRP3, Caspase-1, GSDMD, and IL-1β in colonic tissues to explore the therapeutic mechanism of BXT. ResultCompared with the normal control group, the model group showed increased DAI score, pathological changes in colonic tissues, and up-regulated mRNA and protein expression of NLRP3, Caspase-1, GSDMD, and IL-1β (P<0.05, P<0.01). Compared with the model group, the groups with drug intervention showed reduced DAI scores and improved pathological changes in colonic tissues. The mRNA and protein expression levels of NLRP3, Caspase-1, GSDMD, and IL-1β in colonic tissues of the BXT groups were significantly down-regulated or tended to be down-regulated, especially in the low-dose BXT group (P<0.05, P<0.01). ConclusionBXT can inhibit pyroptosis and alleviate inflammation in rats with UC by regulating the NLRP3/Caspase-1 pathway.
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ObjectiveTo determine the influence of Buzhong Yiqitang on miRNA expression in thyroid tissues of mice with autoimmune thyroiditis (AIT). MethodThirty female 8-week-old NOD.H-2h4 mice were randomly assigned into normal control group, model group, and Buzhong Yiqitang group (BG), 10 in each group. Mice were subjected to a diet containing 0.05% sodium iodide for 8 weeks to build the AIT mouse model. After 8 weeks of administration (ig), samples were collected. A thyroid biopsy was performed on each group of mice, and differential miRNAs in thyroid tissues from each group of mice were analyzed based on experimental validation and bioinformatics. ResultCompared with the conditions of normal control group, thyroid lymphocytes had significant inflammatory infiltration, and there was an increase in serum TgAb level and interleukin(IL)-6 and IL-17 expression and a decrease in IL-1β expression in mice of the model group (P<0.05, P<0.01). In addition, 154 differentially expressed miRNAs were found. Compared with the conditions of model group, the degree of thyroid tissue inflammation was alleviated, and serum TgAb level, and IL-1β, IL-6 and IL-17 expression of mice treated with the Buzhong Yiqitang were reduced (P<0.05, P<0.01). Additionally, 112 differentially expressed miRNAs were identified in the BG group. Validation using real-time polymerase chain reaction(Real-time PCR) showed the same trend for miR-326-3p, miR-128-3p, miR-223-5p, miR-141-3p, miR-871-3p, and miR-204-3p as that obtained from miRNA sequencing. In particular, gene ontology(GO) functions were enriched for regulation of T cell activation, oxidative stress, and miRNA binding. Pathways identified by Kyoto encyclopedia of genes and genomes(KEGG)database tended to be enriched in phosphatidylinositol 3-kinases(PI3K)/protein kinase B(Akt), mitogen-activated protein kinase(MAPK), and cyclic adenosine monophosphate(cAMP) signaling pathways. Based on miRNA prediction differences, three key genes were identified: SMAD3, JAK2, and STAT3. ConclusionBushong Yiqitang might treat autoimmune thyroiditis by regulating 6 miRNAs.
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Neuropathic pain (NP) is a medical problem that has been bothering human beings and seriously affects people's quality of life. Although great progress has been made in the study of NP in recent years, there are still many patients who are ineffective to the existing treatments. At present, drug therapy is still the main method to relieve pain, however, adverse drug reactions has hindered the curative effects of drugs. It is extremely urgent to find new drug targets and reduce the adverse effects of existing drugs. This review will mainly describe the current situation and pathogenesis of neuropathic pain, effectiveness and limitations of existing drugs for treating neuropathic pain, and the current status of drug discovery.
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The chromatic values of the broken-fried and single-fried Gardeniae Fructus Praeparatus(GFP) were measured by the color analyzer to analyze the color variation rule, and the contents of 10 main components were determined by ultra-high performance liquid chromatography(UPLC). The multivariate statistical analysis, Pearson correlation analysis, and discriminant analysis were conducted to investigate the color and components of GFP samples. The experimental results revealed that L~*, a~*, b~*, and E~*ab decreased continuously during processing, and the color of samples gradually deepened. The trend and range of chromatic values during broken-frying and single-frying processes were basically identical. Gardenoside, crocin-Ⅰ(C-Ⅰ), and crocin-Ⅱ(C-Ⅱ) showed an obviously downward trend, while the contents of geniposidic acid and 5-hydroxymethylfurfural(5-HMF) increased significantly. Shanzhiside, deacetyl-asperulosidic acid methyl ester, and geniposide(G2) showed a downward trend. Scandoside methyl ester rose first and fell later. Genipin-1-O-gentiobioside(G1) went through a decrease-increase-decrease trend. The change trends of component contents during broken-frying and single-frying processes were generally consistent, but the change range was different. Among all the components, scandoside methyl ester and G1 showed obvious change. Because of different stir-frying time, the change rate of each component content in the process of broken-frying was higher than that in single-frying process. Additionally, geniposidic acid, gardenoside, scandoside methyl ester, C-Ⅰ, C-Ⅱ, and 5-HMF exhibited a higher correlation with apparent color. On the basis of above findings, the discriminant function of two frying processes was established, which could be applied to the discrimination of broken-fried and single-fried samples. This study analyzed the dynamic quality change rule of GFP during broken-frying and single-frying processes based on color-component correlation analysis, and found the two methods showed consistent change trend, yet with slight difference in the quality of samples. This study can provide data support for the processing of GFP.
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Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Frutas , GardeniaRESUMO
Objective:The correlation between the appearance color of cooked rhubarb samples and the components characterized by high performance liquid chromatography (HPLC) fingerprint was studied to reveal the quality transfer law in the steaming process of processed products with rice-wine. Method:The visual analyzer was used to analyze the change of the appearance color of cooked rhubarb sample powder at different processing time, the common components and their relative peak areas of processed products with rice-wine were identified by HPLC fingerprint, as well as multivariate statistics and Pearson correlation analysis were used to cluster, discriminate and analyze the appearance color and the component variables in HPLC fingerprint. Result:During the processing of cooked rhubarb, the <italic>a</italic><sup>*</sup> (red-green value) of sample powder had no obvious change, but the <italic>L</italic><sup>*</sup> (lightness value), <italic>b</italic><sup>*</sup><italic> </italic>(yellow-blue value) and <italic>E</italic><sup>*</sup><italic>ab </italic>(total chromaticity value) showed a decreasing trend, and the appearance color changed from bright to dark, from yellow to brown. A total of 46 chromatographic peaks in the fingerprint were identified at 254 nm and 280 nm, and 18 of them were identified by comparison with reference standards. The change trend of <italic>L</italic><sup>*</sup>,<italic> b</italic><sup>*</sup><italic> </italic>and <italic>E</italic><sup>*</sup><italic>ab </italic>were positively correlated with the contents of tannins (catechin, epicatechin and ethyl gallate), stilbene glycoside (<italic>trans</italic>-3,5,4′-trihydroxystyryl-4′-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucoside), phenylbutanone glycoside of 4′-hydroxyphenyl-2-butanone-4′-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-[2ʺ-<italic>O</italic>-gallic-6ʺ-<italic>O</italic>-(4ʺ-hydroxy)-cinnamoyl)-glucoside, conjugated anthraquinones (aloe emodin-8-<italic>O</italic>-glucoside, rhein-8-<italic>O</italic>-glucoside, emodin-8-<italic>O</italic>-glucoside) and <italic>ω</italic>-hydroxyemodin (<italic>P</italic><0.05, <italic>P</italic><0.01), and negatively correlated with the contents of free anthraquinones (emodin, aloe emodin and physcion). Compared with 254 nm, the similarities of chromatographic peaks at 280 nm was more obvious, and the number of detected common peaks was more, which could reflect more subtle differences in chemical composition. Conclusion:Tannins, stilbene glycosides and phenylbutanone glycosides are strongly correlated with <italic>L</italic><sup>*</sup>, while anthraquinones are strongly correlated with <italic>b</italic><sup>*</sup>, the decrease of <italic>E</italic><sup>*</sup><italic>ab</italic> is mainly related to the increase of free anthraquinone content and the decrease of catechins, <italic>ω</italic>-hydroxyemodin, stilbene glycosides, conjugated anthraquinone and phenylbutanone glycosides. The change of appearance color index of process samples can reflect the change trend of the contents of medicinal components in cooked rhubarb to some extent.
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Objective:To investigate the mechanism of Xiangsha Liujunzi Tang in improving liver lipid deposition in ApoE<sup>-/-</sup> atherosclerotic (AS) mice by affecting long noncoding RNA-HC (Lnc-HC)/microRNA-130b (miR-130b) in the regulation of cholesterol metabolism. Method:Totolly 10 C57BL/6J mice were selected as normal controls, and 30 healthy ApoE<sup>-/-</sup> mice fed with high fat diet for 12 weeks were then randomly divided into the model group, Xiangsha Liujunzi Tang group(19.12 g·kg<sup>-1</sup>·d<sup>-1</sup>) and simvastatin group(2.275 mg·kg<sup>-1</sup>·d<sup>-1</sup>), with gavage administration for 4 weeks. The serum lipid level of mice was detected by automatic biochemistry analyzer, and the histopathological changes of liver cells were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect expression of long noncoding RNA-HC, and miR-130b. Real-time PCR and Western blot assay were used to detect gene and protein expression of peroxisome proliferator-activated receptor gamma (PPAR<italic>γ</italic>), liver X receptor (LXR), ATP-binding cassette transporters A1 (ABCA1), ATP-binding cassette transporters G1 (ABCG1), ATP-binding cassette transporters G5 (ABCG5), and ATP-binding cassette transporters G8 (ABCG8). Result:Compared with the normal control group, the mice in the model group showed abnormal blood lipids, larger liver cells, obvious fat vacuoles, significantly increased expression of Lnc-HC, miR-130b in liver, and significantly decreased gene and protein expression of PPAR<italic>γ</italic>, LXR, ABCA1, ABCG1, ABCG5, and ABCG8 in mice liver (<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the model group, the abnormal blood lipid levels of the mice in the Xiangsha Liujunzi Tang group and the simvastatin group were improved, and the number of fatty vacuoles of liver cells was significantly reduced, the expression of liver Lnc-HC, miR-130b in Xiangsha Liujunzi Tang group decreased significantly (<italic>P</italic><0.05,<italic>P</italic><0.01), the gene and protein levels of liver PPAR<italic>γ</italic>, ABCA1, ABCG1, ABCG5, ABCG8 in mice of the Xiangsha Liujunzi Tang group and the simvastatin group showed an upward trend. Among them, the gene and protein expression of LXR protein in the liver of the Xiangsha Liujunzi Tang group was significantly up-regulated (<italic>P</italic><0.05). Conclusion:Xiangsha Liujunzi Tang may improve the lipid deposition in the liver of ApoE<sup>-/- </sup>AS mice by affecting Lnc-HC/miR-130b to regulate the cholesterol metabolism process mediated by PPAR<italic>γ</italic>, thus playing a role in preventing and treating AS.
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OBJECTIVES@#Biliary tract cancers (BTCs) are rare but highly fatal. Although the etiology of BTC is poorly understood, gallstones are proposed to be a major risk factor. We conducted a systematic review and meta-analysis to examine the associations between gallstone characteristics and BTC risk. @*METHODS@#We searched the MEDLINE, Embase, and Cochrane Central databases and systematically reviewed cohort and case-control studies published before April 9, 2018. All the included studies reported appropriate risk estimates and confidence intervals (CIs) for associations between the presence, size, number, or duration of gallstones and the risk of BTC, including gallbladder cancer (GBC), extrahepatic bile duct cancer (EBDC), and ampulla of Vater cancer (AOVC). Summary odds ratios (ORs) and their 95% CIs were calculated using a random-effects model in the meta-analysis. Subgroup analyses were conducted to inspect sources of potential heterogeneity, and the Egger test was performed to assess publication bias. @*RESULTS@#Seven cohort studies and 23 case-control studies in Asian, European, and American populations were included. The presence of gallstones was associated with an increased risk of BTC (OR, 4.38; 95% CI, 3.23 to 5.93; I2=91.2%), GBC (OR, 7.26; 95% CI, 4.33 to 12.18), EBDC (OR, 3.17; 95% CI, 2.24 to 4.50), and AOVC (OR, 3.28; 95% CI, 1.33 to 8.11). Gallstone size (>1 vs. <1 cm; OR, 1.88; 95% CI, 1.10 to 3.22) was significantly associated with the risk of GBC. @*CONCLUSIONS@#Gallstone characteristics, such as presence, size, and number, are associated with an increased risk of BTC. However, significantly high heterogeneity in the meta-analyses is a limitation of this study.
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OBJECTIVES@#Biliary tract cancers (BTCs) are rare but highly fatal. Although the etiology of BTC is poorly understood, gallstones are proposed to be a major risk factor. We conducted a systematic review and meta-analysis to examine the associations between gallstone characteristics and BTC risk. @*METHODS@#We searched the MEDLINE, Embase, and Cochrane Central databases and systematically reviewed cohort and case-control studies published before April 9, 2018. All the included studies reported appropriate risk estimates and confidence intervals (CIs) for associations between the presence, size, number, or duration of gallstones and the risk of BTC, including gallbladder cancer (GBC), extrahepatic bile duct cancer (EBDC), and ampulla of Vater cancer (AOVC). Summary odds ratios (ORs) and their 95% CIs were calculated using a random-effects model in the meta-analysis. Subgroup analyses were conducted to inspect sources of potential heterogeneity, and the Egger test was performed to assess publication bias. @*RESULTS@#Seven cohort studies and 23 case-control studies in Asian, European, and American populations were included. The presence of gallstones was associated with an increased risk of BTC (OR, 4.38; 95% CI, 3.23 to 5.93; I2=91.2%), GBC (OR, 7.26; 95% CI, 4.33 to 12.18), EBDC (OR, 3.17; 95% CI, 2.24 to 4.50), and AOVC (OR, 3.28; 95% CI, 1.33 to 8.11). Gallstone size (>1 vs. <1 cm; OR, 1.88; 95% CI, 1.10 to 3.22) was significantly associated with the risk of GBC. @*CONCLUSIONS@#Gallstone characteristics, such as presence, size, and number, are associated with an increased risk of BTC. However, significantly high heterogeneity in the meta-analyses is a limitation of this study.
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Objective::To analysis the effect of Huayu Qutan recipe on myocardial fibrosis in atherosclerotic rabbits based on mitochondrial fusion-lysis. Method::The 36 SPF healthy male rabbits were selected, and 6 rabbits were selected randomly as the normal group, and given normal pellet feed, another 30 rats were fed with high fat diet to establish atherosclerosis model.After successful replication of animal models, they were randomly divided into model group, Huayu Qutan recipe low-dose, medium-dose and high-dose group (4.0, 8.0, 16.0 g·kg-1) and simvastatin group (1.4 mg·kg-1), 6 rats each.Each group was given corresponding drugs according to the dosage, continuous administration for 4 weeks.The serum lipid levels in rabbits of each group were detectived by automatic biochemical analyzer, the degree of myocardial fibrosis was measured by Masson staining, and expression levels of mitochondrial fusion protein 1 (Mitofusin 1), mitochondrial fusion protein 2 (Mitofusin 2), optic atrophy protein 1 (Opa1), promoter protein 1 (Drp1), mitogen 1 (Fis1) in myocardial tissue were detected by immunohistochemistry. Result::Compared with normal group, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) in model group were significantly increased, levels of density lipoprotein cholesterol (HDL-C) were significantly decreased, the expression levels of Mitofusin 1, Mitofusin 2 and Opa1 in myocardial tissue were significantly decreased, the expression levels of Drp1 and Fis1 were significantly increased(P<0.05, P<0.01), compared with model group, the levels of serum TC, TG, LDL-C in simvastatin group and Huayu Qutan recipe low-dose, medium and high-dose group were significantly decreased, levels of HDL-C were significantly increased, the expression levels of Mitofusin 1, Mitofusin 2 and Opa1 in myocardial tissue were significantly increased, the expression levels of Drp1 and Fis1 were significantly decreased (P<0.05, P<0.01), compared with the Huayu Qutan recipe high-dose group, the levels of serum TC, TG, LDL-C in simvastatin group and Huayu Qutan recipe low, medium-dose group were significantly increased, the expression levels of Mitofusin 1, Mitofusin 2 and Opa1 in myocardial tissue were significantly decreased, the expression levels of Drp1 and Fis1 were significantly increased(P<0.05, P<0.01). Conclusion::Huayu Qutan recipe can effectively regulate blood lipid and inhibit myocardial fibrosis in atherosclerotic rabbits, and the higher the dose of Huayu Qutan recipe, the more obvious the effect is, it is speculated that its effect may be related to the regulation of the expression of mitochondrial fusion-lysis related proteins such as Mitofusin1, Mitofusin2 and Opa1, Drp1 and Fis1 in myocardial cells.
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Purpose@#This was a descriptive study to compare the characteristics and outcomes among deceased cancer patients that had do-notattempt-resuscitation (DNAR) agreements in hospice and oncology wards. @*Methods@#Subjects of this study were 250 patients with terminal cancer who died after making DNAR agreements from January 1, 2015 to December 31, 2016 . The subjects were divided into two groups those that died in hospice (n=150) and those that died in oncology wards (n=100). Data were collected from August 2017 to February 2018. Two trained investigators independently reviewed the medical records for subjects using survey tools developed by the researchers (r=.81). @*Results@#Among the general characteristics between two groups, there were differences in age (t=-2.54, p=.012) and education (χ2=5.96, p=.015). Among the disease related characteristics, there were differences in surgery history (χ2=10.09, p=.001), chemotherapy history (χ2=11.08, p=.002) and symptoms (t=5.14, p<.001) between the two groups. Among the treatment related characteristics, there were differences in chemotherapy at death (χ2=9.61, p=.002), radiotherapy at death (χ2=5.60, p=.018) and cardiopulmonary resuscitation (χ2=6.15, p=.029) between the two groups. Among nursing related characteristics, there was a difference in the frequency of nursing intervention after DNAR consent (t=3.72, p<.001) between the two groups. Among outcomes related characteristics, there were differences in consciousness state at the DNAR consent (χ2=64.82, p<.001), self-written consent (χ2=18.26, p=.001), hospitalization days (t=2.31, p=.022) and the cost per day of hospitalization (t=-4.81, p<.001) between the two groups. @*Conclusion@#This study found that the patients, families, and medical staff need to change their perception of hospice and palliative care to prevent medical expenses from rising due to unnecessary life-support treatment while preparing for death with family members.
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Several epidemiological studies suggest a potential association between gallstones or cholecystectomy and hepatobiliary and pancreatic cancers (HBPCs). The aim of this study was to evaluate the risk of HBPCs in patients with gallstones or patients who underwent cholecystectomy in the Korean population. A retrospective cohort was constructed using the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Gallstones and cholecystectomy were defined by diagnosis and procedure codes and treated as time-varying covariates. Hazard ratios (HRs) in relation to the risk of HBPCs were estimated by Cox proportional hazard models. Among the 704,437 individuals who were included in the final analysis, the gallstone prevalence was 2.4%, and 1.4% of individuals underwent cholecystectomy. Between 2002 and 2015, 487 and 189 individuals developed HBPCs in the gallstone and cholecystectomy groups, respectively. A significant association was observed between gallstones and all HBPCs (HR 2.16;95% CI 1.92-2.42) and cholecystectomy and all HBPCs (HR 2.03; 95% CI 1.72-2.39). However, when 1-, 3-, and 5-year lag periods were applied, the HBPC and subsites risk approached zero. A significant association was observed between cholecystectomy and intrahepatic bile duct cancer (IBDC) (HR 2.68; 95% CI 1.63-4.40). When 1-, 3- and 5-year lag periods were applied, the IBDC risk after cholecystectomy was 2.86-fold (95% CI 1.68-4.85), 2.92-fold (95% CI 1.51-5.64), and 4.08-fold (95% CI 1.94-8.61) higher, respectively, than that in the comparison group. In conclusion, gallstone diagnosis and cholecystectomy seem to correlate with HBPCs, especially cholecystectomy and IBDC.
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OBJECTIVE@#To screen the antioxidant small molecular compounds with optimal efficiency of expansing the human hematopoietic stem cells (hHSC) In vitro based on antioxidant small molecular compound database of LKT laboratory, and to verify the effects of these compounds on the biological functions of hHSC.@*METHODS@#The umbilial cord blood CD34 cells were enriched by using the MACS beads; the absolute number and percentage of CD34 cells and CD34 CD49f cells were detected by high throughput flow cytometry after culture of hHSC with compounds in vitro for 1 week, the SR1 (1 μmol/L) was used as positive control, the candidate compounds were screened out; then 4 compounds were selected for follow-up experiments by comprehensive evaluation of concentration, safety and expansion efficacy, the optimal used concentrations of selected compounds were determined through the concentration gradient analysis, and CFC short-term colony-forming cell test was performed by using the determined concentration so as to verify the effect of compounds on the self-renewal, multilineage differentiation.@*RESULTS@#Out of 85 antioxidant small molecular compounds, 4 compounds (C2968, D3331, B1753 and B3358) with obvious expansion efficacy for CD34 cells and CD34 CD49f cells were screened out by high throughput flow cytometry; their optimal concentrations of 4 compounds were 0.5 μmol/L for C2968, 1.5 μmol/L for D3331 and 1.5 μmol/L for B1753 and 15 μmol/L for B3358. The CFC assay showed the colony formation number in compound-treated group significantly increased as compared with control group, moreover the self-renewal and multilineage differentiation were maintained.@*CONCLUSION@#The antioxidant small molecular compounds C2968 (0.5 μmol/L), D3331 (1.5 μmol/L), B1753 (1.5 μmol/L) and B3358 (1.5 μmol/L) possess good expansion efficacy for hHSC, they can maintain hHSC self-renewal, at the same time ensure the multilineage differentiation potentiality of hHSC.
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Humanos , Antígenos CD34 , Antioxidantes , Células Cultivadas , Sangue Fetal , Citometria de Fluxo , Células-Tronco HematopoéticasRESUMO
Objective: To observe the changes of dysfunctional high density lipoprotein cholesterol (dyHDL) and the intervention effect of Xiangsha Liu Junzitang in rats with spleen deficiency and hyperlipidemia, and reveal the effect and mechanism of Xiangsha Liu Junzitang on dyHDL in rats with spleen-deficiency hyperlipidemia. Method: Seventy-five SPF SD rats were randomly divided into normal group, high fat group, spleen deficiency and high fat group, Xiangsha Liu Junzitang low and high dose groups (5.67, 11.34 g·kg-1). In the spleen deficiency and high fat group, as well as Xiangsha Liu Junzitang low and high dose groups, composite method of improper diet and exhaustive swimming was used for 15 days for modeling. After modeling for 15 days, normal group was fed with basic diet, while the high-fat group, spleen-deficiency and high-fat group, the Xiangsha Liu Junzitang low and high dose groups were fed with high-fat diet. After 12 weeks, the Xiangsha Liu Junzitang low dose and high dose groups received corresponding dosage of drugs, while normal group, high fat group and spleen deficiency high fat group received corresponding volume of normal saline. After 4 weeks, the contents of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol cholesterol (LDL-C), and high density lipoprotein cholesterol(HDL-C)were detected by automatic biochemistry analyzer, while D-xylose excretion rate was measured by phloroglucinol method. The morphological changes of liver cells were observed by hematoxylin eosin (HE) staining. The level of PON1, apoA1 and SAA in plasma were detected by enzyme-linked immunosorbent assay (ELISA). Paraoxonase 1(PON1), apolipoprotein A1 (apoA1) and serum amyloid protein A (SAA) gene expression in rats liver were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result: As compared with normal group, the serum TC, TG, and LDL-C levels were significantly increased in the high-fat group and spleen-deficiency high-fat group (PPPPPPD-xylose excretion rate was significantly decreased in the spleen-deficiency and high-fat group (PPPPPPPPConclusion: The lipid disorder in hyperlipidemia rats was aggravated by the spleen deficiency, but was corrected after intervention with Xiangsha Liu Junzitang. and its mechanism may be related to the regulation of the expression of dyHDL-related genes and protein.
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Objective: To investigate the expression changes of mitogen activated protein kinase(MAPK) signaling pathway-related genes in ApoE-/- mice and the intervention effect of Huayu Qutan recipe on them, in order to explore the anti-atherosclerotic(AS) effect and possible mechanism of Huayu Qutan recipe. Method: Fifty ApoE-/- mice were randomly divided into model group, tanshinone ⅡA group (30 mg·kg-1·d-1), and high-dose phlegm group (20 g·kg-1·d-1), the middle-dose group (10 g·kg-1·d-1), and the low-dose group (5 g·kg-1·d-1), and 10 C57BL/6/J mice were included in the blank controls group. Automated biochemical analyzer was used to detect serum triglyceride(TG), cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C) content; hematoxylin-eosin(HE) was used to detect aortic plaque in each group; oil red O was used to detect liver lipid deposition in each group; enzyme-linked immuno sorbent assay(ELISA) was used to determine vascular cell adhesion protein-1(VCAM-1), intercellular adhesion molecule-1(ICAM-1), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) in serum of each group; Western blot was performed to detect c-Jun N-terminal kinase (JNK), phosphorylated c-Jun N-terminal kinase(p-JNK), c-Jun N-terminal kinase(JNK), p38 MAPK, p-p38 MAPK, extracellular regulated protein kinases (ERK), and expression of p-ERK. Result: Compared with the blank control group, serum TC, TG, LDL-C levels in the model group were significantly increased, while HDL-C levels were significantly decreased; aortic plaques were observed in the aortic lumen, and lots of lipid deposition were observed in the liver cells. Serum inflammatory factors TNF-α, IL-6, VCAM-1, ICAM-1 increased(PPα, IL-6, VCAM-1 and ICAM-1 were decreased. The expressions of p-p38 MAPK and p-JNK genes in intravascular associated MAPK signaling pathway were significantly decreased. p-ERK expression trend was not obvious(PConclusion: Huayu Recipe can inhibit the formation of aortic plaque in ApoE-/- mice, and its mechanism may be related to the regulation of vascular MAPK signaling pathway gene expression.
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Objective To evaluate the relationship between p38mitogen-activated protein kinase (p38MAPK) signaling pathway and calcium over-loading during oxygen-glucose deprivation and restoration (OGD/R) in cardiomyocytes of rats.Methods Cardiomyocytes obtained from Sprague-Dawley rats,aged 1-3 days,were cultured and divided into 3 groups (n =27 each) using a random number table method:control group (group C),group OGD/R and p38MAPK inhibitor SB203580 group (group SB).The cells were subjected to OGD for 6 h followed by restoration of O2-glucose supply for 2 h.Ceils were incubated for 1 h with 10 μmol/L SB203580 in group SB.At 2 h of restoration of O2-glucose supply,cell morphology was observed under an inverted microscope,cell viability was measured by the CCK-8 method,the release of lactate dehydrogenase (LDH) in the supernatant was determined by 2,4-dinitrobenzene chromogenic method,intracellular calcium concentration was determined by flow cytometry,and the expression of phosphorylated p38MAPK (p-p38MAPK) and p38MAPK was detected using Western blot.The LDH release rate and p-p38MAPK/p38MAPK ratio were calculated.Results Compared with group C,the LDH release rate,intracellular calcium concentration and p-p38MAPK/p38MAPK were significantly increased,and the cell viability was markedly decreased in group OGD/R and group SB (P<0.05).Compared with OGD/R group,the LDH release rate,intracellular calcium concentration and p-p38MAPK/p38MAPK ratio were significantly decreased,the cell viability was increased (P<0.05),the cell morphology was nearly normal,and the number of cells was increased in group SB.Conclusion p38MAPK signaling pathway can mediate calcium overload after being activated and is involved in the pathophysiological mechanism of OGD/R in cardiomyocytes of rats.
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To investigate the amelioration effect of saponins extracted from Panax japonicas (SPJ) on myocardial fibrosis in natural aging rats and its mechanisms, male SD rats aged 18 months were randomly divided into 3 groups (aging model group, low-dose SPJ group and high-dose SPJ group), with 10 rats in each group. SPJ groups were given SPJ at different doses (10, 60 mg·kg⁻¹·d⁻¹) consecutively for 6 months, meanwhile, aging model group was treated with the equal volume of saline for 6 months until 24 months old. Another 10 rats aged 6 month were used as young control group. The changes of myocardial morphological were observed by haematoxylin-eosin (HE) staining. Masson staining was used to observe the changes of collagen deposition in rat hearts. RT-PCR was used to detect the mRNA expression levels of myofibroblast marker α-SMA, collagen-related protein COL1α2, COL3α1 and matrix metalloproteinase MMP2, MMP9. Western blot was used to test the changes of the protein expressions of TGF-β1, p-Smad3, IL-1β and TNF-α in heart tissues. SPJ can effectively improve the arrangement of myocardial fibers, decrease inflammatory infiltration and reduce collagen deposition in aging rats. SPJ can effectively down-regulate the mRNA expression levels of COL1α2, COL3α1, α-SMA, MMP9, MMP2 and inhibit the protein expressions of TGF-β1, p-Smad3, TNF-α, IL-1β in the natural aging heart tissues. SPJ can effectively alleviate myocardial fibrosis in natural aging rats, and its mechanisms was related to the inhibition of the protein expressions of TGF-β1, p-Smad3 and the reduction of myocardial inflammation in rat hearts.
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Animais , Masculino , Ratos , Fibrose , Panax , Ratos Sprague-Dawley , Saponinas , Transdução de Sinais , Proteína Smad3 , Fator de Crescimento Transformador beta1RESUMO
We studied the disinfection effect of a new ultraviolet (UV) sterilizer and its utilization on ultrasound probe surfaces. Carrier quantitative germicidal tests, simulated on-the-spot trials, and organic substance influence tests were used to carry out experimental observation. Artificially infected probes were disinfected using the sterilizer or a germicidal lamp for comparison. The total number and types of bacteria were determined and identified. Our results demonstrated the sterilizer had the best disinfection effect among three different disinfection methods in hospital. The sterilizer has been used in a hospital setting for 2 years with no notable damage to the ultrasound probe instrument. It has the advantages of fast disinfection, high disinfection effect, and good compatibility with the ultrasound instrument, worthy of being a promoted application in medical institutions.