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ObjectiveMalignant tumor has become a serious public health problem， threatening human health. Chinese herbal medicine has become a research focus as it is "simple， convenient， inexpensive， and effective" and exerts anti-tumor effect through "multiple components， multiple targets， and multiple pathways". This paper reviews the anti-tumor effect of triterpenes， polysaccharides and other compounds in Poria， which is expected to serve as a reference for research on the anti-tumor effect of Poria. MethodBasic research， clinical observation， and reviews were retrieved from PubMed， Google Scholar， and China National Knowledge Infrastructure （CNKI） （1995—2022） with the keywords of Poria and malignant tumor. ResultThe main active components of Poria such as triterpenes represented by pachymic acid and polysaccharides represented by pachyman had extensive pharmacological effects in inhibiting the proliferation of malignant tumors， inducing apoptosis， suppressing invasion and metastasis， regulating the immune function， and improving the quality of life. In addition， the cultivation method， medicinal part， growth environment， and harvest cycle of the medicinal plant， and dosage form and processing method of Poria affected the content of different active components. ConclusionThe active components of pachymic acid and triterpenoids have great potential in antitumor， which， however， face the challenges in innovation and quality clinical trials. The lack of quality control standard of Poria may affect the anti-tumor effect， and efforts should be made to formulate specific standard for quality control. The antitumor of Poria is science-based and thus it has broad application prospect. Nevertheless， more efforts should be made before the practical application.
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Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.
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Animals , Mice , Proto-Oncogene Proteins c-akt , Phosphatidylinositol 3-Kinases , Prediabetic State , Vascular Endothelial Growth Factor A , Interleukin-6 , Transcriptome , Tumor Suppressor Protein p53 , Insulin , CholesterolABSTRACT
OBJECTIVE To explore the material basis and potential mechanism of Kazakh classic prescription Wuzdekh （WZDK） in the treatment of enteritis. METHODS LC-MS/MS technology was used to analyze the chemical components in WZDK. Through network pharmacology and molecular docking technology， the main chemical components of WZDK were screened and the target was predicted； therapeutic effect and target of WZDK on acute enteritis were verified through in vivo experiments. The acute enteritis model of mice was induced by dextran sulfate sodium salt； the general condition of the mice was observed during administration and the disease activity index （DAI） score was calculated； pathological changes of the intestine and mRNA expression of core target were validated by HE staining and quantitative real-time PCR. RESULTS A total of 316 chemical components were obtained by LC-MS/MS. The core targets of network pharmacological analysis mainly included interleukin 1β（IL- 1β）， protein kinase B1 （AKT1）， tumor protein p53 （TP53）， IL-6， tumor necrosis factor （TNF） and so on. The results of molecular docking showed that chemical components such as mairin， lappadilactone， costunolide and dehydrocostus lactone were stable in binding to the core target. The results of in vivo experiment showed that， compared with model group， high dose （5.00 g/kg） of WZDK could significantly reduce the DAI score （P＜0.05）， improve inflammatory cell infiltration and mucosal tissue damage of colon tissue， and significantly down-regulated mRNA expressions of IL-6， TNF-α， IL-1β and TP53 in colon tissue（P＜ 0.05 or P＜0.01）. CONCLUSIONS Chemical components of WZDK such as mairin， lappadilactone， costunolide and dehydrocostus lactone may play the role of improving the imbalance of local inflammatory factors in the intestine and repairing damage of colonic mucosal tissue by down-regulating mRNA expressions of TNF-α， IL-6， IL-1β and TP53 in colon tissue.
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Objective:To determine the expression of transglutaminase 2 (TGM2) in peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD), and to analyze its correlation with AD-related inflammatory factors and disease severity.Methods:A total of 29 AD patients and 15 healthy controls were collected from the First Affiliated Hospital of Fujian Medical University from July 2020 to January 2021. Ten milliliters of peripheral blood samples were collected from each subject, so was the clinical information, including age, gender, course of disease, eosinophil counts, basophil counts, total IgE levels, Scoring AD index (SCORAD), etc. PBMCs were isolated by density gradient centrifugation. Fluorescence-based quantitative PCR was performed to determine the mRNA expression of TGM2 and AD-related inflammatory factors (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17, thymic stromal lymphopoietin [TSLP], P2RX7 [purinergic receptor P2X, ligand-gated ion channel, 7], etc.) in PBMCs from 29 AD patients and 15 healthy controls, and flow cytometry to determine TGM2 protein expression on PBMCs. Mann-Whitney U test was used to analyze differences between groups, and Spearman correlation analysis to evaluate the correlation. Results:The relative mRNA expression of TGM2 in PBMCs did not differ between the AD group and control group ( M[ Q1, Q3]: 0.509 [0.325, 0.958] vs. 0.475 [0.328, 1.051], U = 210.50, P = 0.872). Compared with the control group, the AD group showed significantly decreased IL-4 mRNA expression (0.171[0.049, 0.449] vs. 0.824 [0.397, 1.378], P < 0.001), but significantly increased mRNA expression of IL-8 and IL-13 ( P = 0.011, 0.006, respectively). Spearman correlation analysis showed that the mRNA expression level of TGM2 in PBMCs was positively correlated with the mRNA expression levels of IL-4 and P2RX7 in the AD group ( rs = 0.42, 0.40, P = 0.024, 0.034, respectively), while there were no correlations between TGM2 mRNA expression and AD severity-related indicators (all P>0.05), such as age (21[16, 29] years), course of disease (4[1,10] years), eosinophil counts (0.33[0.18, 0.65] × 10 9/L), basophil counts (0.04[0.03, 0.06] × 10 9/L], SCORAD scores (60.5[46.98, 66.13] points), and serum total IgE levels (373 [40, 1 815] IU/ml). The relative protein expression levels of TGM2 on the surface of PBMCs did not differ between the AD group and control group (54.9 [47.6, 62.8] vs. 55.55 [51.5, 60.25], U = 112.00, P = 0.922) ], and no correlations were observed between the protein expression of TGM2 on PBMCs and AD severity-related indicators in the AD group (all P > 0.05) . Conclusion:No significant differences were observed in TGM2 mRNA expression in PBMCs or TGM2 protein expression on the surface of PBMCs between the AD patients and healthy controls, and there were no correlations between the TGM2 mRNA and protein expression and AD severity.
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Objective:To investigate the prevalence of malnutrition in elderly patients with neurological diseases and the of nutrition, and to explore their association with clinical outcomes.Methods:A retrospective study was conducted to analyze 566 elderly patients with neurological diseases in the database of the "National Multicenter Survey on the Dynamic Changes of Nutritional Status of Hospitalized Patients" by using the Global leadership Initiative on Malnutrition(GLIM)criteria and subjective global assessment(SGA). The two diagnostic tools for malnutrition were compared to explore the correlation between malnutrition and clinical outcomes.Results:Based on the GLIM criteria, 83 cases were diagnosed with malnutrition and the incidence of malnutrition was 14.66%(83/566), with 14.72%(48/326)in men and 14.58%(35/240)in women.Patients with moderate malnutrition accounted for 8.30%(47/566)and patients with severe malnutrition accounted for 6.36%(36/566). According to the SGA, the incidence of moderate malnutrition(SGA Grade B)was 15.55%(88/566), the incidence of severe malnutrition(SGA Grade C)was 1.94%(11/566), and all cases of malnutrition(SGA Grade B+ C)accounted for 17.49% of the participants(99/566). The total length of hospital stay was(15.46±6.49)days in the malnutrition group and(13.55±5.09)days in the non-malnutrition group, with a statistical difference between the two groups( t=-3.02, P<0.01). The body weight of the malnutrition group was significantly lower than non-malnutrition group[(52.0±8.5)kg vs.(65.2±9.6)kg, t=12.92, P<0.01]. There were also statistically significant differences in BMI(19.1±2.7 kg/m 2vs.23.9±2.6 kg/m 2, t=15.48, P<0.01), upper arm circumference[(22.3±2.5)cm vs.(28.3±3.9)cm, t=7.01, P<0.01], and lower leg circumference[(28.9±3.4)cm vs.(32.5±3.3)cm, t=6.81, P<0.01]between the two groups.Laboratory tests showed that there were significant differences in lymphocytes[(5.0±8.5)×10 9/L vs.(9.4±11.8)×10 9/L, t=3.61, P<0.01]and albumin[(38.5±4.4)g/L vs.(40.7±5.1)g/L, t=3.18, P<0.01]between the malnutrition group and the non-malnutrition group.The correlation between GLIM and SGA was good, and the consistency was reasonable(AUC=0.711). Conclusions:The incidence of malnutrition in elderly patients with neurological diseases is relatively high; The GLIM criteria are suitable for the diagnosis of malnutrition in elderly patients with neurological diseases, and the diagnostic results have a good correlation with those of SGA.Malnutrition is associated with anthropometric measurements, laboratory indicators, and clinical outcomes.
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Objective:To analyze the correlation between nutritional status and frailty and sarcopenia in geriatric inpatients (GIPs) planning to receive major hepatopancreatobiliary (HPB) surgery.Methods:From December, 2020 to September, 2022, GIPs who were planning to receive major HPB surgery were recruited. Nutritional assessment was performed using nutritional risk screening 2002 (NRS-2002) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Frailty and sarcopenia assessment were performed using Fried frailty phenotype (FFP) and Asian Working Group for Sarcopenia (AWGS) 2019 consensus on sarcopenia diagnosis and treatment. The prevalence and concurrence of malnutrition, frailty and sarcopenia were investigated, and the correlation between nutritional status and frailty and sarcopenia was analyzed.Results:A total of 144 participants at the mean age of (70.10±7.44) years were included. The prevalence of nutritional risk, malnutrition, and severe malnutrition were 73.6% ( n ?=?106), 68.1% ( n ?=?98), and 34.7% ( n ?=?50) respectively. The prevalence of frailty was 20.8% ( n ?=?30) and that of sarcopenia was 35.4% ( n ?=?51). The prevalence of severe malnutrition increased significantly in older participants and the prevalence of nutritional risk, malnutrition and severe malnutrition decreased significantly with higher BMI. The prevalence was 35.4% (51/144) for concurrent sarcopenia and malnutrition, 19.4% (28/144) for frailty and malnutrition, 14.6% (21/144) for sarcopenia and weakness, and 14.6% (21/144) for sarcopenia, malnutrition, and weakness. There was a positive correlation between nutritional risk and frailty ( r = 0.603, P < 0.001). The risk of pre-frailty and frailty in the nutritional risk group was higher than that in the non-nutritional risk group ( χ 2 = 31.830, P < 0.001). The risk of pre-frailty and frailty in the malnutrition group was higher than that in the normal nutrition group ( χ 2 = 36.727, P < 0.001). Logistic regression analysis showed that the risk of frailty in patients with severe malnutrition was 12.303 times higher than that in patients with normal nutrition status (95% CI: 2.592 to 58.409, P = 0.002). The risk of sarcopenia in the nutritional risk group was higher than that in the non-nutritional risk group ( χ 2 = 13.982, P < 0.001). The risk of sarcopenia in the malnutrition group was higher than that in the normal nutrition group ( χ 2 = 37.066, P < 0.001). Conclusions:The prevalence and concurrence rate of malnutrition, frailty, and sarcopenia are high in GIPs undergoing major HPB surgery. GIPs with malnutrition are susceptible to frailty.
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Objective:To study the association of frailty status with nutritional risk and the effect on clinical outcomes among elderly surgical inpatients.Methods:Elderly inpatients from the surgery department of Beijing Hospital were enrolled from January to June 2021. Frail scale and nutritional risk screening 2002 (NRS 2002) were used for frailty evaluation and nutrition risk screening. The influence of frailty and associated nutrition risk in elderly surgical inpatients was analyzed.Results:487 elderly surgical patients were included, of whom 131 cases were in the non-frailty group, 279 cases were in the pre-frailty group and 77 cases were in the frailty group, according to the Frail scale score. 146 cases were at nutritional risk, of whom 8 (6.1% of 131) were in the non-frailty group, 87 (31.2% of 279) in the pre-frailty group and 51 (66.2% of 77) were in the frailty group. According to univariate/multivariate logistic regression analysis of frailty in elderly surgical patients, a higher NRS 2002 score, older age, and the presence of multiple concurrent diseases (≥ 5) were significantly associated with frailty ( P < 0.001). The Frail scale score was positively correlated with NRS 2002 score ( r = 0.448, P < 0.01). Multiple comparisons showed that frailty had statistically significant effects on hospital stay and medical costs in elderly surgical patients ( P < 0.05). Conclusions:The prevalence of frailty is higher in elderly surgical patients, and the prevalence of nutritional risk increases with the progression of frailty. Frailty can lead to prolonged hospital stays and increased hospital costs in elderly surgical patients.
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Objective:To retrospectively investigate the incidence of malnutrition in patients with gastric cancer in China, and to explore the applicability of Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria.Methods:Data were extracted from National Multi-center Investigation and Study on Dynamic Changes of Nutritional Status of Inpatients database led by Geriatric Nutrition Support Group of the Chinese Society of Parenteral and Enteral Nutrition. A retrospective analysis in patients with gastric cancer was conducted. Involuntary weight loss, low body mass index (BMI) and muscle mass loss were adopted as phenotypic indicators in GLIM criteria for malnutrition diagnosis and the application of GLIM criteria for malnutrition diagnosis in patients with gastric cancer was evaluated.Results:In a total of 563 gastric cancer patients, 203 cases were diagnosed with malnutrition per GLIM criteria and 193 cases without malnutrition were identified as control using 1:1 propensity score matching. There were significant differences in body weight, BMI, right calf circumference, right hand grip strength, total cholesterol, hemoglobin, albumin and total protein between malnutrition group and non-malnutrition group ( P < 0.05). After muscle mass loss was removed from the phenotype indicators in GLIM criteria, the hospitalization duration in patients with malnutrition was (16.15±7.04) days compared with (14.28±6.70) days in patients without malnutrition, demonstrating statistically significant difference ( χ2= 0.442, P = 0.007). Conclusions:Gastric cancer patients showed high incidence of malnutrition. The cut-off value of calf circumference reported in foreign populations may be unsuitable to apply in Chinese population. Further clinical researches are needed to determine the optimal cut-off calf circumference value for Chinese individuals.
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Objective:To analyze the relationship between nutritional status and frailty among elderly inpatients from cardiology department.Methods:A cross-sectional study was conducted in a total of 519 patients aged 65-92 years old who were admitted to cardiology department between September 2018 and February 2019. Mini nutritional assessment short form (MNA-SF) was used to assess the nutritional status. Fried phenotype was used to assess frailty status. The nutritional status and frailty in patients with different diseases, age and body mass index were analyzed, as well as the nutritional status of patients in different frailty strata.Results:The mean age was 75.12 years (range: 65-92 years). The prevalence of malnutrition risk was 28.9% (150/519), malnutrition 3.3% (17/519) and frailty 23.5% (122/519). When stratified by disease, the subgroup with chronic heart failure showed the highest prevalence of malnutrition and frailty (63.6% and 50.0%, respectively). The prevalence of malnutrition risk (22.8%, 35.5%), malnutrition (3.0%, 3.6%) and frailty (15.3%, 32.3%) were higher in patients ≥ 75 years compared with those aged 65 years - 75 years. MNA-SF score was negatively correlated with age( r = -0.134, P = 0.002). Fried phenotype score was positively correlated with age ( r = 0.319, P < 0.01). As for stratification based on BMI, the majority (62.6%) patients were overweight or obese (BMI ≥ 24.0 kg/m 2) and the prevalence of malnutrition risk in this subgroup was 21.2% (69/325). The prevalence of malnutrition risk in patients with normal BMI was 38.7% (70/181). The subgroup with BMI<18.5 were either at malnutrition risk or with malnutrition. MNA-SF score was positively correlated with BMI ( r = 0.353, P < 0.01). There was no significant difference in the prevalence of pre-frailty and frailty among different BMI groups. The prevalence of malnutrition was the highest in the frailty group (8.2%), followed by the pre-frailty group (2.0%). Fried phenotype score was negatively correlated with MNA-SF score( r = -0.291, P < 0.01). Logistic regression analysis showed that frailty was an independent risk factor for malnutrition, and the risk of malnutrition in frailty patients was 4.818 (95% CI:1.701～13.644) times higher than that in non-frailty patients. Conclusions:The prevalence of malnutrition risk and frailty was high in the elderly inpatients from cardiology department. Frailty patients had a higher incidence of malnutrition and required more attention.
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Objective:To investigate the protective effect of overexpressed tripartite motif containing (TRIM27) on severe acute pancreatitis (SAP) in mice and its possible mechanism.Methods:Twenty-four mice were randomly divided into the sham operation + control virus group (AAV-GFP group), sham operation + overexpression of TRIM27 group (AAV-TRIM27 group), SAP + control virus group (SAP+AAV-GFP group), SAP + overexpression of TRIM27 group (SAP + AAV-TRIM27 group), with 6 mice in each group. SAP model of mice was established by intraperitoneal injection of L-arginine (4 mg/kg). The sham operation group was injected with equal volume of normal saline, and the virus group was injected with control or TRIM27 overexpression adeno-associated virus (2×10 11 μg/ per mice). The serum and pancreatic tissue samples were collected 72 h after modeling. The levels of serum amylase, lipase, tumor necrosis factor α (TNF-α), interleukin-1b (IL-1b), IL-6, macrophage chemoattractant protein-1 (MCP-1) and the expression of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) in pancreatic tissue were detected by enzyme-linked immunosorbent assay. Hematoxylin eosin staining was used to observe the pathological damage of pancreatic tissue. The expressions of myeloperoxidase (MPO) and Ly6g positive inflammatory cells in mouse pancreas were observed by immunohistochemistry. The expression of p-p65, p65, p-ASK1, ASK1, p-JNK, JNK, p-p38 and p38 in pancreatic tissue were detected by Western blot. Results:The expression of TRIM27 in pancreatic of mice was significantly down regulated after SAP ( P<0.05); after overexpression of TRIM27 by adeno-associated virus, the expression of TRIM27 in mouse pancreas was significantly up-regulated ( P<0.05). There was no significant difference in the indexes of mice between the AAV-GFP group and AAV-TRIM27 group ( P>0.05). Compared with the SAP + AAV-GFP group, the levels of serum amylase, lipase, TNF-α, IL-1b, IL-6 and MCP-1 in mice of the SAP + AAV-TRIM27 group were significantly decreased, MDA in pancreatic tissue was decreased, SOD and GSH were increased, MPO and Ly6g inflammatory cells were significantly decreased, and p-p65, p-ASK1, p-JNK, and p-p38 protein expression were down regulated. Conclusions:Overexpression of TRIM27 alleviates SAP in mice by inhibiting inflammatory response and oxidative stress, and its mechanism may be through inhibiting NFκB/MAPK signaling pathway.
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ObjectiveTo observe the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation， apoptosis， and migration of cancer-relative endothelial （CRE） cells， and to decipher the mechanism of XLJDP in regulating angiopoietin2 （Ang2） to maintain CRE cell homeostasis and inhibit tumor neovascularization. MethodHuman umbilical vein endothelial cell line （HUVEC-c） was induced into CRE cells in the human colorectal cancer HCT-116 cell-conditioned medium. The CRE cells were assigned into the blank group， conditioned medium group， and XLJDP groups （1， 2， 3 g·L-1） and treated for 48 h. The proliferation of CRE cells was detected by methyl thiazolyl tetrazolium （MTT） colorimetry. The morphological changes of CRE cells were observed via an inverted microscope. The apoptosis rate was detected by flow cytometry. Wound healing test and Transwell migration assay were employed to detect the 2D/3D migration ability of CRE cells. The protein levels of vimentin， N-cadherin， matrix metalloproteinase-9 （MMP-9）， and Ang2 in CRE cells were measured by Western blot. ResultThe MTT results showed that the cell viability was higher in the conditioned medium group than in the blank group （P<0.05）. Compared with the conditioned medium group， XLJDP decreased the cell proliferation rate （P<0.01） and changed the cell morphology. The total apoptosis rates of all the XLJDP groups were higher than that of the conditioned medium group （P<0.01）. The 2D and 3D migration abilities of the conditioned medium group were higher than those of the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations weakened the 2D migration ability （P<0.01） and medium- and high-concentration XLJDP weakened the 3D migration ability （P<0.01）. The protein levels of N-cadherin， Vimentin， MMP-9， and Ang2 were up-regulated in the conditioned medium group compared with those in the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations down-regulated the protein level of Ang2 （P<0.05， P<0.01）， and medium- and high-concentration XLJDP down-regulated those of N-cadherin， vimentin， and MMP-9 protein （P<0.01）. ConclusionXLJDP may inhibit the proliferation， migration， differentiation， and apoptosis of CRE cells by down-regulating the expression of Ang2， inhibiting tumor neovascularization， and maintaining the cell homeostasis.
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ObjectiveTo study the effect of Xianlian Jiedu prescription （XLJDP） on the activation of nuclear transcription factor-κB （NF-κB） signaling pathway induced by bromodomain-containing protein 4 （Brd4） in hypoxic microenvironment and to explore its mechanism in inhibiting the proliferation of colorectal cancer HT-29 cells. MethodThe human colorectal cancer HT-29 cells were cultured in a hypoxic incubator or normoxia incubator and treated with XLJDP at 0.8，1，1.2，1.6，3.2，6.4，and 12.8 g·L-1 for 48 h， respectively. Following the detection of cell vitality using methyl thiazolyl tetrazolium （MTT） colorimetry， the effects of XLJDP （1.25，2.5，and 5 g·L-1） on the cell mitochondrial membrane potential were determined using a fluorescent probe （JC-1）， and the apoptosis of colorectal cancer HT-29 cells was detected by flow cytometry. The cell colony formation assay and 5-ethynyl-2'-deoxyuridine （EDU） staining were conducted to test the proliferation of colorectal cancer HT-29 cells. The Western blot was carried out to measure the expression levels of Brd4 and its downstream relevant proteins such as c-Myc and hexamethylene bisacetamide-inducible protein 1 （HEXIM1）， as well as the effects of XLJDP on related proteins in the NF-κB signaling pathway. ResultCompared with the blank control group， XLJDP at 0.8，1，1.2，1.6，3.2，6.4，and 12.8 g·L-1 inhibited the vitality of colorectal cancer HT-29 cells （P<0.05 ， P<0.01）， with the median inhibitory concentration （IC50） under the hypoxic condition higher than that under the normoxia condition. Compared with the blank control group， XLJDP at 1.25，2.5，and 5 g·L-1 significantly decreased the mitochondria membrane potential， enhanced the apoptosis （P<0.05，P<0.01）， and lowered the number of cell colonies and also the EDU-positive cells （P<0.05， P<0.01）. The results of Western blot showed that compared with the blank control group， XLJDP at 1.25，2.5，and 5 g·L-1 down-regulated Brd4， c-Myc， p-NF-κB p65， and p-IκBα protein expression to varying degrees and up-regulated the expression of HEXIM1 （P<0.05， P<0.01）. ConclusionIn the hypoxic microenvironment， XLJDP inhibits the proliferation of colorectal cancer HT-29 cells regulated by Brd4， which may be related to its inhibition of the activation of NF-κB signaling pathway.
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ObjectiveTo explore the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation and glycolysis of human colorectal cancer HCT-116 cells and the underlying mechanism. MethodHCT-116 cells were cultured with XLJDP and then the survival rate was examined by methyl thiazolyl tetrazolium （MTT） assay. The effect on the HCT116 cell proliferation was detected by colony formation assay and 5-ethynyl-2′-deoxyuridine （EDU） incorporation assay. The amount of glucose consumed by HCT-116 cells was measured by glucose test kit， and the amount of produced lactic acid was determined by lactic acid test kit 48 h after the treatment with XLJDP. The expression of glycolysis-related proteins mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）， glucose transporter 1 （GLUT1）， and lactate dehydrogenase （LDHA） was detected by Western blot. ResultThe half-maximal inhibitory concentration （IC50） of XLJDP against HCT-116 cells was 6.82 g·L-1. Compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L-1） inhibited the proliferation of HCT-116 cells （P<0.05， P<0.01）. Moreover， compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L-1） suppressed glucose uptake and lactic acid production in a dose-dependent manner （P<0.05， P<0.01）. The expression of p-mTOR/mTOR， LDHA， and GLUT1 was down-regulated by XLJDP （P<0.05， P<0.01）. ConclusionXLJDP can significantly inhibit the proliferation and the Warburg effect of glycolysis in colorectal cancer cells by regulating the mTOR signaling pathway and the down-regulating the expression of LDHA， GLUT1， and other key proteins and enzymes in glycolysis.
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ObjectiveTo analyze the transcriptome characteristics of Xianlian Jiedu prescription （XLJDP） in the intervention of colorectal carcinoma by high-throughput cDNA-sequencing （RNA-seq）. MethodNinety male C57BL/6 mice were randomly divided into the control group， colorectal carcinoma due to dampness， heat， stasis， and toxin model group， and XLJDP group， with 30 mice in each group. Mice in the model group and XLJDP group were fed a high-fat diet and provided with azoxymethane and dextran sodium sulfate （AOM/DSS） for inducing colorectal carcinoma. Those in the XLJDP group were further treated with intragastric administration of 12.9 g·kg-1 XLJDP since the day of modeling for 112 days. The colorectal tissues were collected from each group 4 h after the last drug treatment and stained with hematoxylin-eosin （HE） and methylene blue for observing the pathological changes. The total RNA was extracted from colorectal tissues for RNA-Seq-based transcriptome profiling， followed by gene oncology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis and the screening and verification of differentially expressed genes. ResultCompared with the model group， XLJDP significantly relieved the colorectal congestion and edema and decreased tumor number and volume in mouse colorectal tissues. The methylene blue staining results indicated that XLJDP significantly suppressed the development of aberrant crypt foci （ACF，P<0.01）. As revealed by HE staining， XLJDP significantly alleviated the injury and dysplasia of colorectal tissues. Transcriptome analysis identified 615 differentially expressed genes （446 up-regulated and 169 down-regulated） between the model group and the blank group and 54 differentially expressed genes （29 up-regulated and 25 down-regulated） between the XLJDP group and model group. XLJDP mainly affected the expression of NIMA-related protein kinase 7 gene （Nek7， P<0.01）， Mucin 16 （Muc16， P<0.01）， SiahE3 ubiquitin protein ligase family member 3 （Siah3， P<0.01）， regenerating islet-derived protein 3-gamma （Reg3g， P<0.01）， RNA polymerase Ⅱ elongation factor-associated factor 2 （Eaf2， P<0.01）， transforming growth factor‐alfa gene （TGF-α， P<0.05）， secretoglobin family 1A member 1 （Scgb1a1， P<0.05）， family with sequence similarity 227 member B （Fam227B， P<0.05）， cytochrome P450 family 2 subfamily c polypeptide 40 （Cyp2c40， P<0.01）， and ankyrin repeat and EF-hand domain containing protein 1 （Ankef1， P<0.05）. Enrichment analysis showed that intestinal epithelial cell proliferation， metabolism of xenobiotics by cytochrome P450， and arachidonic acid metabolism signaling pathway were significantly enriched. ConclusionXLJDP is able to interfere with colorectal tumorigenesis and development due to dampness， heat， stasis， and toxin in mice， which has been proved by transcriptome analysis to be related to the regulation of metabolism-related pathways.
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Objective@#To explore the effect of puberty on refractive development of children and adolescents and its interaction with outdoor activities, near work and the use of electronic products, so as to provide a reference for strategies for intervening myopia.@*Methods@#Cluster sampling method was used to select 776 students aged 7-13 from a nine year consistent school in Shanghai to participate and were followed up for 2 years. All participants underwent cycloplegic refraction and ocular axial length measurement once a year, as well as pubertal development, average daily outdoor time, near work time and time of electronic products usage. The influencing factors and interaction effects of refractive parameters in different puberty stages were analyzed by generalized estimation equation.@*Results@#At baseline, 634 children participated in cycloplegic refraction, of which 350 were myopic (55.2%). There were significant differences in axial length, average daily outdoor time, near work time and time of using electronic products at different stages of puberty ( F = 4.10 ，4.24，5.54，9.20， P <0.05). There was interaction between puberty and outdoor time on axial length development ( β =0.133, P < 0.05), and the interaction between puberty and the time of near work or using electronic products was not statistically significant ( P >0.05).@*Conclusion@#Puberty may play a regulatory role in the relationship between outdoor time and refractive development among Chinese children and adolescents.
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The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 μm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 μL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.
Subject(s)
Chemometrics , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid , Scutellaria , Tandem Mass Spectrometry/methodsABSTRACT
Objective:To analyze the correlation among nutritional status, sarcopenia and frailty in elderly inpatients with chronic cardiovascular disease.Methods:A cross-sectional study was conducted in a total of 147 patients aged 65-88 years old who were hospitalized for chronic cardiovascular disease between September 2018 and February 2019. Nutritional status was assessed by mini nutritional assessment short form (MNA-SF), frailty by FRAIL scale and sarcopenia by criteria from Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. The prevalence and overlapping prevalence of nutritional status, frailty and sarcopenia were analyzed, as well as the influence of nutritional status on frailty and sarcopenia.Results:The mean age was 74.45 (range: 65-88). The prevalence was 25.9% (38/147) for risk of malnutrition, 1.4% (2/147) for malnutrition, 37.4% (55/147) for risk of sarcopenia, 6.8% (10/147) for sarcopenia, 55.8% (82/147) for pre-frailty and 10.2% (15/147) for frailty. When stratified by disease, the subgroup with chronic heart failure showed the highest prevalence of malnutrition risk, sarcopenia risk, sarcopenia and frailty (66.7%, 50%, 16.7% and 50.0%, respectively). The prevalence of sarcopenia risk and sarcopenia increased with age. Age was negatively correlated with calf circumference ( r = -0.219, P = 0.008), grip strength ( r = -0.307, P < 0.01) and walking speed ( r = -0.390, P < 0.01) and was positively correlated with the five times sit-to-stand test time ( r = 0.406, P < 0.01). The prevalence of frailty also increased with age and age was positively correlated with the FRAIL score ( r = 0.232, P = 0.005). As for stratification based on BMI, the majority (63.9%) patients were overweight or obese (BMI ≥ 24.0) and the prevalence of malnutrition risk in this subgroup was 20.2% (19/94). The prevalence of malnutrition risk in patients with normal BMI was 32.0% (16/50). The subgroup with BMI < 18.5 were either at malnutrition risk or with malnutrition. MNA-SF score was positively correlated with BMI ( r = 0.334, P < 0.01). The prevalence of sarcopenia risk and sarcopenia in patients with BMI ≥ 24.0 kg/m 2 was 23.4% (22/94) and 2.1% (2/94), that in normal BMI subgroup was 62.0% (31/50) and 14.0% (7/50), and that in BMI < 18.5 subgroup was 66.7% (2/3) and 33.3% (1/3). BMI was positively correlated with calf circumference ( r = 0.659, P < 0.01) and ASMI ( r = 0.367, P < 0.01). The overlapping prevalence of sarcopenia risk/sarcopenia and malnutrition risk/malnutrition was 13.6% (20/147), that of pre-frailty/frailty and malnutrition risk/malnutrition was 21.8% (32/147), and that of sarcopenia risk/sarcopenia and pre-frailty/frailty was 26.5% (39/147). The overlapping prevalence of sarcopenia risk/sarcopenia, malnutrition risk/malnutrition and pre-frailty/frailty was 10.9% (16/147). MNA-SF score was negatively correlated with FRAIL score ( r = -0.316, P < 0.01). The prevalence of pre-frailty/frailty in the malnutrition risk/malnutrition group was higher than that in the subgroup with normal nutritional status (80.0% vs. 60.7%, χ 2 = 4.808, P = 0.028). The prevalence of sarcopenia risk/sarcopenia in the malnutrition risk/malnutrition group tended to be higher than that in the subgroup with normal nutritional status (50.0% vs. 33.6%, χ 2 = 3.302, P = 0.069). Logistic regression analysis showed that the risk of pre-frailty/frailty was 2.585 (95% CI: 1.087 to 6.147) times higher in the malnutrition risk/malnutrition group. Conclusions:The prevalence and overlapping prevalence of malnutrition risk, pre-frailty and sarcopenia risk was high in the elderly inpatients hospitalized for chronic cardiovascular disease. Patients with malnutrition risk/malnutrition had a higher incidence of pre-frailty/frailty and required close attention.
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Objective:The aim of the present study was to observe the effects of liralutide on body composition and muscle function in adult obese patients with type 2 diabetes.Method:A total of 63 adult obese type 2 diabetic patients who were (52.6±9.7) years of age and with body mass index (BMI) of ≥28 kg/m 2 were enrolled. The patients were randomly assigned into two groups. On the basis of maintaining the original hypoglycemic regimen, patients in the control group ( n=24) were given dietary guidance only, and those in the treatment group ( n=39) were injected with liraglutide. All patients were followed up for a period of 12 weeks. Blood glucose, glycosylated hemoglobin(HbA1c) and insulin levels, liver and kidney function, body composition assessed with electrical impedance methods, and grip strength measured by a grip meter for muscle function were detected at the baseline and the end of the study. Results:Compared with those in the control group, the reductions in HbA1c [(-1.54±2.10) % vs.(-0.53±0.84) %], body weight [(-3.46±4.2) kg vs.(-0.34±3.66) kg], body fat mass [(-1.97±2.98) kg vs.(-0.01±2.16) kg] and visceral fat area [(-0.01±2.16) cm 2 vs.(0.34±6.39) cm 2] were more pronouced in liraglutide treated group (all P<0.05). However, no changes could be observed in muscle mass and grip strength after liraglutide treatment. Conclusions:In addition to reducing blood glucose, body weight and fat mass, treatment with lilaluptide had no impact on muscle mass and muscle function. Therefore, liralutide is suitable for obese patients with type 2 diabetes, especially for weight management patients who are at risk of muscle loss.
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Objective:To analyze the prevalence of malnutrition in stable-phase elderly patients with chronic obstructive pulmonary disease (COPD) using the Global Leadership Initiative on Malnutrition (GLIM) criteria.Methods:Using cross-sectional survey, 60 elderly patients with COPD in stable phase were investigated, with 72 elderly patients without COPD in the same age group selected as controls. Differences in basic characteristics, anthropometric indicators, hematology indicators and body composition were compared between the two groups. According to the GLIM diagnostic criteria for malnutrition, the first step is nutritional risk screening, the second step is to diagnose malnutrition, and the third step is to determine severe malnutrition. The prevalence of malnutrition and severe malnutrition were investigated.Results:The levels of total protein, albumin, creatinine, and lymphocyte percentage in the elderly stable COPD group were significantly lower than those in the control group. The nutritional risk and the prevalence of malnutrition in elderly COPD patients were significantly higher than those in the control group, and the prevalence of severe malnutrition was higher .Conclusions:Elderly stable COPD patients of different age groups have a higher nutritional risk. The onset age of malnutrition is younger than that of non-COPD patients and early intervention is required.
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Objective:To investigate the predictive value of dynamic platelet and hemagglutination-related parameters in patients with acute pancreatitis (AP).Methods:The patients admitted to the Department of Emergency Surgery in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2020 were analyzed. According to the inclusion criteria and exclusion criteria, patients with AP were retrospectively enrolled. According to the Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis (Shenyang, 2019), the patients were divided into two groups: severe acute pancreatitis (SAP group) and non-severe acute pancreatitis (non-SAP group) [including mild acute pancreatitis (MAP) and moderate severe acute pancreatitis (MSAP)]. A normal distribution of the maximum and mean aggregation rates of dynamic platelets (arachiidonic acid), plateletcrit (PCT) and bedside index for severity in acute pancreatitis (BISAP) scores and other measurement data were tested by t test, while measurement data of prothrombin time (PT), fibrinogen (FIB) and D-dimer that did not conform to normal distribution were tested by Mann-Whitney U test. χ 2 test was used for the counting data such as sex, age and etiology of patients in the two groups. The prognostic value of statistically significant indicators for non-SAP group and SAP group was further analyzed by receiver operating characteristic (ROC) curve. Results:A total of 146 patients with AP were enrolled, including 50 patients in SAP group and 96 in non-SAP group. The maximum and average aggregation rates of dynamic platelet (aracidonic acid) in the SAP group were (71.76±17.62) % and (67.91±18.10) %, PT (12.02±1.33) s, FIB (4.76±2.08) g/L, D-dimer (3.75±6.04) μg/L, PCT (0.23±0.08) %, and BISAP scores (1.42±1.18), which were all significantly higher than those in the non-SAP group [the maximum and average aggregation rates of dynamic platelet (arachiidonic acid) (46.65±20.11) % and (42.50±20.71) %, PT (11.50±1.51) s and FIB (3.91±1.48) g/L, D-dimer (1.00±1.37) μg/L, PCT (0.19±0.06) %, BISAP scores (0.45±0.66)] (all P<0.05). According to area under the ROC curve, the maximum and average aggregation rates of dynamic platelets (arachiidonic acid) in serum of patients with SAP were 0.83 and 0.82, respectively, and the sensitivities were 0.56 and 0.68, respectively. The specificity was 0.99 and 0.81, respectively, which was better than PT, FIB, D-dimer, PCT and BISAP scores in predicting the severity of AP. Conclusions:The maximum and average aggregation rates of dynamic platelets (arachidonic acid), PT, FIB, D-dimer, PCT and BISAP scores can be used as predictors of the severity of acute pancreatitis. The maximum and average aggregation rates of dynamic platelets (arachiidonic acid) were the best in predicting the severity of AP.