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ObjectiveTo investigate the effect of Yishen Tongluo prescription （YSTLP） on apoptosis of renal tubular epithelial cells and explore the mechanism based on endoplasmic reticulum stress pathway of protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4）/transcription factor C/EBP homologous protein （CHOP）. MethodThe db/db mice were randomly divided into model group， valsartan group （10 mg·kg-1）， and low， middle， high-dose YSTLP groups （1， 2.5， 5 g·kg-1）. Samples were collected after eight weeks of drug intervention. In addition， db/m mice in the same litter served as the control group. Human renal tubular epithelial cells （HK-2） were cultured in vitro and divided into the control group， advanced glycated end-product （AGE） group， and AGE + low， middle， and high-dose YSTLP groups （100， 200， 400 mg·L-1）. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect the apoptosis rate of HK-2 cells. Methylthiazolyldiphenyl-tetrazolium bromide （MTT） assay was conducted to detect the viability of HK-2 cells. Calcium fluorescence probe staining and luciferase reporter gene method were adopted to detect the luciferase activity of folded protein response element （UPRE） and endoplasmic reticulum stress. Immunohistochemical （IHC） analysis was carried out to measure the protein expressions of phosphorylated PKR （p-PERK）， CHOP， and ATF4. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of CHOP and X-box binding protein 1 （XBP1） in mouse kidney and HK-2 cells. Western blot was used to detect the protein expression level of p-PERK， PERK， CHOP， ATF4， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and cleaved Caspase-3 in mouse kidney and HK-2 cells. ResultIn the cellular assay， HK-2 cell viability was significantly reduced， and the apoptosis rate was elevated in the AGE group compared with the control group （P<0.01）. The mRNA and protein expression levels of apoptosis-related factor Bcl-2 were significantly reduced （P<0.01）， and those of Bax were significantly increased （P<0.01）. The protein expression level of cleaved Caspase-3 was significantly increased （P<0.01）. Compared with the AGE group， YSTLP administration treatment resulted in elevated cell viability and reduced apoptosis rate （P<0.01）. The mRNA and protein expression levels of Bcl-2 were significantly elevated in a time- and dose-dependent manner （P<0.01）， and those of Bax were significantly reduced in a time- and dose-dependent manner. The protein expression level of cleaved Caspase-3 was significantly reduced in a time- and dose-dependent manner （P<0.01）. The intracellular Ca2+ imbalance and UPRE luciferase fluorescence intensity were increased in the AGE group compared with the control group （P<0.01）. The mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 were significantly increased （P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the AGE group， YSTLP effectively improved intracellular Ca2+ imbalance in HK-2 cells and decreased UPRE luciferase fluorescence intensity in a dose-dependent manner （P<0.01）. It reduced the mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 （P<0.01） and the protein expression levels of intracellular p-PERK， CHOP， and ATF4 in a dose- and time-dependent manner （P<0.01）. In animal experiments， the protein expression level of Bcl-2 was significantly reduced（P<0.01）， and that of cleaved Caspase-3 and Bax was significantly increased in the model group compared with the control group （P<0.05）. The protein expression level of Bcl-2 was dose-dependently elevated， and that of cleaved Caspase-3 and Bax was dose-dependently decreased in the YSTLP groups compared with the model group （P<0.01）. Compared with the control group， the mRNA expression levels of CHOP and XBP1 were significantly elevated in the model group （P<0.05， P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the model group， YSTLP significantly decreased the mRNA expression levels of CHOP and XBP1 （P<0.01） and the protein expression levels of p-PERK， CHOP， and ATF4 （P<0.01）. ConclusionYSTLP can effectively inhibit endoplasmic reticulum stress and improve apoptosis of renal tubular epithelial cells， and its mechanism may be related to the regulation of the PERK/AFT4/CHOP pathway.
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Objective:To screen the main active components of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression; To predict the key targets and signaling pathways; To establish a multi-level network structure and comprehensively reveal the synergistic mechanism of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression.Methods:Main components of Danggui Buxue Decoction were searched in TCMSP detabase, combined with literature reports to supplement and improve information. The protein targets of compounds were standardized in the UniProt protein database. Myelosuppression targets were obtained by querying TTD database, GeneCards database, DrugBank detabase and OMIM database. The effective components and common targets of Danggui Buxue Decoction were screened, and the protein-protein interaction (PPI) network of intersection targets was analyzed by String platform to construct the PPI network of effective components and disease targets. Gene ontology (GO) analysis and enrichment pathway analysis of Kyoto gene and genome encyclopedia (KEGG) of key target proteins were conducted through Metascape data platform. Both the results of GO and KEGG analysis were presented. AutoDock software was used for molecular docking to explore the interaction between core targets and active components, and the results were imported into PyMOL software for visual analysis.Results:Danggui Buxue Decoction has a total of 22 active components of Chinese materia medica for improving chemotherapy-induced myelosuppression, 294 potential targets, 3 301 disease targets, and 210 common targets of Chinese materia medica and diseases. Core targets were obtained through network topology analysis and molecular docking. The first five were ESR1, MAPK1, RELA, AKT1, PIK3R1; GO enrichment results obtained 2 430 biological processes, 125 cellular components and 217 molecular functions, including responses to inorganic substances, membrane rafts, micro-organisms membrane region, transcription factor binding, etc.; KEGG enriched 385 pathways, of which cancer pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, etc. were the main signaling pathways; molecular docking results showed that β-sitosterol has the best binding performance with HSP90AA1, formononetin and RELA in astragalus when it was in Angelicae Sinensis Radix.Conclusion:Danggui Buxue Decoction regulates ESR1, MAPK1, RELA, AKT1 and other core targets through various active components such as quercetin, formononetin, and β-sitosterol. PI3K-AKT and other related signaling pathways can improve chemotherapy-induced myelosuppression and provide a basis for its clinical application.
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Objective:To investigate the risk factors of early neurological deterioration (END) in patients with minor ischemic stroke caused by large vessel occlusion (LVO) and the impact of rescue endovascular thromboectomy (REVT) on clinical outcomes of patients with END at discharge.Methods:Consecutive patients with acute minor ischemic stroke caused by LVO within 24 h of onset in the Third Affiliated Hospital, Soochow University from January 2021 to March 2023 were retrospectively enrolled. Minor ischemic stroke was defined as baseline National Institute of Health Stroke Scale (NIHSS) score ≤5 at admission. END was defined as an increase of ≥4 in the NIHSS score within 24 h after the best medical management. The modified Rankin Scale was used to evaluate the clinical outcomes of patients with END at discharge. 0-2 was defined as a good outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for END and the impact of REVT on clinical outcomes in patients with END. Results:A total of 75 patients with minor ischemic stroke caused by LVO were included, of which 31 (41.3%) developed END and 13 (41.9%) underwent REVT after END. Multivariate logistic regression analysis showed that internal carotid artery occlusion was an independent risk factor for END (odds ratio 4.304, 95% confidence interval 1.213-15.270; P=0.024), and REVT was an independent protective factor for good outcomes in patients with END (odds ratio 0.068, 95% confidence interval 0.006-0.774; P=0.030). Conclusions:The incidence of END is higher in patients with minor ischemic stroke caused by LVO, and internal carotid artery occlusion is an independent risk factor for the occurrence of END. Providing REVT after END may improve the clinical outcomes of patients with END at discharge.
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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death, and most patients with HCC are diagnosed at an advanced stage. Before 2017, tyrosine kinase inhibitors were the main drugs for the treatment of advanced hepatocellular carcinoma. With the emergence of immune checkpoint inhibitors (ICIs), immunotherapy has gradually brought new hope to such patients. At present, the combination of ICIs and other systemic or local treatments has become a potential strategy for the treatment of advanced hepatocellular carcinoma, and some of these combinations have been included in large-scale clinical trials. The main challenges of immunotherapy for advanced hepatocellular carcinoma include the exploration of predictive biomarkers, management of immune-related adverse events, and exploration of effective combination regimens. This article provides the latest research progress on the single or combined use of ICIs and other immunotherapy for hepatocellular carcinoma and discusses the limitations of current research and clinical application and the future development direction.
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OBJECTIVE To investigate the improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steatohepatitis （NASH）. METHODS Normal human liver LO2 cells were induced to steatosis by free fatty acid， then were divided into normal group， model group， silybin group （100 μmol/mL）， T. yunnanensis ethanol extracts （TYS） group （50 μg/mL）， T. yunnanensis ethyl acetate extracts （TYSA） group （50 μg/mL）， and T. yunnanensis n-butanol extracts （TYSB） group （50 μg/mL）. After 24 hours of drug intervention， the deposition of lipid droplets was observed in LO2 cells in each group. The contents of total cholesterol （TC）， triacylglycerol （TG）， malondialdehyde （MDA） and glutathione （GSH）， the activities of aspartate transaminase （AST）， alanine transaminase （ALT） and superoxide dismutase （SOD）， the mRNA expressions of Kelch-like ECH-associated protein 1（ Keap1）， nuclear factor E2-related factor 2（ Nrf2） and heme oxygenase 1（ HO- 1） were detected. NASH rat model was induced by a high-fat diet， and then divided into normal group， model group， silybin group （12.6 mg/kg）， TYS group （80 mg/kg）， TYSA group （80 mg/kg） and TYSB group （80 mg/kg）， with six rats in each group. The liver indexes of rats in each group were calculated after 6 weeks of drug intervention. The liver histopathological changes were observed， and the contents of TC， TG， HDL-C and LDL-C， AST and ALT activities in serum， the contents of MDA and GSH， SOD activities in liver tissue were detected. RESULTS Compared with model group， TYS， TYSA and TYSB could reduce lipid droplet deposition， intracellular TC， TG and MDA contents， AST and ALT activities， and increase SOD activity， GSH content， and Keap1， Nrf2， HO-1 mRNA expression levels in LO2 cells after steatosis to varying degrees， with some differences being statistically significant （P＜0.05）. They also significantly improved liver injury in NASH model rats， reduced their liver indexes， TC， TG， LDL-C and MDA contents， AST and ALT 1-042） activities， and increased HDL-C （except for TYS and TYSB）， GSH contents and SOD activity， with TYSA having the most significant effect （P＜0.05）. CONCLUSIONS TYS， TYSA and TYSB have a certain improvement effect on NASH， among which TYSA has the most obvious effect. Its mechanism of action may be related to upregulating the Keap1/Nrf2/HO-1 signaling pathway and inhibiting oxidative stress
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Background@#and Purpose We performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of genetically proxied AMP-activated protein kinase (AMPK) activation, which is the target of metformin, on functional outcome following ischemic stroke onset. @*Methods@#A total of 44 AMPK-related variants associated with HbA1c (%) were used as instruments for AMPK activation. The primary outcome was the modified Rankin Scale (mRS) score at 3 months following the onset of ischemic stroke, evaluated as a dichotomous variable (3–6 vs. 0–2) and subsequently as an ordinal variable. Summary-level data for the 3-month mRS were obtained from the Genetics of Ischemic Stroke Functional Outcome network, including 6,165 patients with ischemic stroke. The inverse-variance weighted method was used to obtain causal estimates. The alternative MR methods were used for sensitivity analysis. @*Results@#Genetically predicted AMPK activation was significantly associated with lower odds of poor functional outcome (mRS 3–6 vs. 0–2, odds ratio [OR]: 0.06, 95% confidence interval [CI]: 0.01–0.49, P=0.009). This association was maintained when 3-month mRS was analyzed as an ordinal variable. Similar results were observed in the sensitivity analyses, and there was no evidence of pleiotropy. @*Conclusion@#This MR study provided evidence that AMPK activation by metformin may exert beneficial effects on functional outcome following ischemic stroke.
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@#The human gut microbiota regulates many host pathophysiological processes including metabolic, inflammatory, immune and cellular responses. In recent years, the incidence and mortality of lung cancer have increased rapidly, which is one of the biggest challenges in the field of cancer treatment today, especially in non-small cell lung cancer. Animal models and clinical studies have found that the gut microbiota of non-small cell lung cancer patients is significantly changed compared with the healthy people. The gut microbiota and metabolites can not only play a pro-cancer or tumor suppressor role by regulating immune, inflammatory responses and so on, but also be related with radiotherapy and chemotherapy of non-small cell lung cancer and the resistance of immunotherapy. Therefore, gut microbiota and related metabolites can be both potential markers for early diagnosis and prognosis in patients with non-small cell lung cancer and novel therapeutic targets for targeted drugs. This study will review the latest research progress of effect of gut microbiota on non-small cell lung cancer, and provide a new diagnosis and treatment ideas for non-small cell lung cancer.
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Objective Optimizing the extraction process of prescription medicinal materials of hospital preparation of compound Yangshe granules. Methods A high performance liquid chromatograph (HPLC) quantitative method was established for deacetyl asperulosidicacid methyl ester (DME) and ferulic acid (FC) of the active ingredient. Based on the content of DME, FC and the yield of extract, the extraction process of compound Yangshe granule extract was optimized using central composite design-response surface methodology. Results The established HPLC method of quantification of active components in compound Yangshe granules met the requirements of method validation. The optimal extraction process optimized by central composite design-response surface methodology were as follows: the weight of extraction solvent was 12 times of the medicinal slices, the alcohol concentration was 73% and the extraction time was 60 min. Conclusion In this study, the quantitative method of active components in compound Yangshe granule by HPLC has been successfully established, and the optimized extraction process is simple and easy to operate with good repeatability.
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The mortality and disability of patients with acute basilar artery occlusion (ABAO) are extremely high without endovascular therapy. However, there is a lack of clear criteria for screening people who benefit from endovascular therapy for patients with ABAO. A large number of studies have shown that the collateral circulation status is crucial to judge the clinical outcome of patients with ABAO after endovascular therapy. The posterior circulation collateral scoring systems have been proposed according to different imaging methods. This article reviews the posterior circulation collateral scores and thier predictive value in ABAO patients treated with endovascular therapy.
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Objective:To explore the mechanism of lysosomal membrane permeabilization(LMP)inuranyl acetate-induced death of human kidney proximal tubular epithelial HK-2 cells.Methods:HK-2 cells were exposed to uranyl acetate at concentrations of 100, 300 and 600 μmol/L for 24 h, then in tracellular reactive oxygen species (ROS)and mitochondrial superoxide were measured by DCFH-DA and MitoSOX probe, respectively. HK-2 cells were divided into four groups: blank control group, NAC or CA-074 Me group, uranyl acetate exposure group and uranyl acetate exposure plus NAC or CA-074 Me group. Two-color immune of luorescence staining was used to detect the co-localization of galectin-1 and lysosomal associated membrane protein-1 (LAMP-1) to measure the extent of LMP, and to detect the non- co-localization of cathepsin B and LAMP-1 to reflect the release of cathepsin B in lysosomes. Calcein-AM/PI double staining method was used to detect cell death. One-color immune of luorescence staining of cleaved-caspase-3 expression was used to detect apoptosis. Results:Intracellular ROS and mitochondrial superoxide levels were significantly increased in HK-2 cells after exposure with 100, 300 and 600 μmol/L uranyl acetate for 24 h, about 1.1-2.5 times or 4.0-28 times, respectively( tROS=17.98, 11.84, 11.75, P< 0.05; tmitochondrial superoxide=6.14, 16.02, 13.06, P< 0.05), and they also increased with uranyl acetate concentrations ( tROS=10.10, 10.37, 5.59, P< 0.05; tmitochondrial superoxide=21.50, 15.16, 5.93, P< 0.05). The percentage of co-localization of galectin-1 and LAMP-1 and the percentage of non- co-localization of cathepsin B and LAMP-1 were markedly increased in HK-2 cells after exposure with 600 μmol/L uranyl acetate for 24 h, 5.4-6.7 times or 1.5-2.1 times, respectively ( tGalectin-1=15.85, 12.70, P< 0.05; tCathepsin B=5.95, 6.69, P< 0.05), but these increases were inhibited by NAC ( tGalectin-1=4.74, P<0.05; tCathepsin B=4.51, P< 0.05). Moreover, the cell death rate and the cleaved-caspase-3 expression level were also significantly increased in HK-2 cells after exposure with 600 μmol/L uranyl acetate for 24 h, about 28-47 times or 2.4-6.0 times, respectively( tPI=30.40, 10.34, P<0.05; tCleaved-caspase-3=18.49, 9.52, P<0.05), and these increases were obviously diminished by CA-074 Me ( tPI= 6.76, P<0.05; tCleaved-caspase-3=13.47, P<0.05). Conclusions:Exposure to uranyl acetate induces a burst of intracellular ROSthat leads to LMP and consequently causes leakage of cathepsin B from lysosomes to cytoplasm, in turn triggering the lysosomal-dependent cell death and mitochondrial-regulated apoptosis of HK-2 cells.
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Objective:To investigate the effects of inhibition of Wnt/ β-catenin signaling pathway on paraquat (PQ)-induced transition of human lung fibroblast cell line MRC-5 and related molecular mechanisms.Methods:The MRC-5 cells were divided into three groups. Control group: without drug treatment; PQ group: the cells were treated by PQ (50 μmol/L) for 72 hours to establish cell transition model; PQ+DKK1 group: the cells were treated with PQ (50 μmol/L) and DKK1 (10 ng/mL) for 72 hours. Then, the cells were collected, and the transition related signatures including α-SMA, Vimentin and Collagen I were detected by immunofluorescence and Western blot (WB); Meanwhile, the expression levels of Wnt pathway-related molecules including β-catenin, Cyclin D1 and WISP1 were determined by WB, immunofluorescence and real-time fluorescence quantitative PCR (RT-PCR) during the transition; In addition, the inhibitor of Wnt/β-catenin pathway Dickkopf-1 (DKK1) was applied to block the signaling. Then the expression changes of β-catenin, cyclin D1 and WISP1 were detected by WB to verify the inhibitory effect, and the transition marker molecules including α-SMA, Vimentin and Collagen I were also determined by WB.Results:After 72 hours, compared with the Control group, the expression levels of α-SMA, Vimentin and Collagen I of MRC-5 cells in PQ group were increased significantly ( P<0.05); The expression levels of β-catenin, Cyclin D1 and WISP1 of MRC-5 cells in PQ group were significantly up-regulated ( P<0.05); DKK1 could inhibit the high expression of α-SMA, Vimentin and Collagen I of MRC-5 cells during PQ-induced transition ( P<0.05). Conclusions:DKK1 could inhibit PQ-induced transition of lung fibroblasts by interference with Wnt/β-catenin signaling, which was expected to further inhibit pulmonary fibrosis caused by PQ.
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ObjectiveThe pulmonary edema （PE） model where the disease was located in the viscera was established according to the treatment principle that patients with the disease location inside should be treated with descending and sinking medicine， combined with changes in the disease tendency， to verify the scientificity of descending and sinking properties of Descurainiae Semen Lepidii Semen （SD）， and to preliminarily elucidate the scientific connotation of descending， ascending， floating and sinking of Chinese medicine. MethodSixty male SD rats were randomly divided into normal control group， model group （20 mg·kg-1）， positive drug group （dexamethasone， 0.075 mg·kg-1） and SD low （1.167 g·kg-1）， medium （2.334 g·kg-1）and high （4.668 g·kg-1） dose groups. The PE model was established by intrapleural injection of 1% carrageenan （2 mL·kg-1）. The evaluation indexes （lung autopsy， amount of pleural effusion， number of white blood cells， lung wet/dry weight ratio， lung water content and lung permeability） were tested to determine the optimal dose of SD decoction for intervention of PE. The relevant indexes of the five major systems （central nervous system， respiratory system， circulatory system， digestive system and urinary system） closely related to the body's Qi movement were detected and changes in the disease tendency in PE rats were analyzed， to determine the descending， ascending， floating and sinking properties of SD. In addition， histopathological changes were investigated by hematoxylin-eosin （HE） staining， and types and numbers of inflammatory cells and mediators were detected to preliminarily explore the mechanism of SD in improving PE. ResultCompared with the conditions in the normal control group， the amount of pleural effusion， number of white blood cells in pleural effusion， lung wet/dry weight ratio， lung water content and lung permeability were increased （P<0.01） in the model group， where the rats presented cough， dyspnea， shortness of breath and arched back， and a small number of them had wet nose and bubble liquid in nostrils. In the autopsy of the rats in the model group， the lungs were enlarged or accompanied by congestion and plenty of pink bubble liquid appeared at the trachea. Compared with the conditions in the model group， SD reduced the amount of pleural effusion， number of white blood cells in pleural effusion， lung coefficient， lung wet/dry weight ratio and lung water content （P<0.01）， and improved pulmonary edema symptoms such as damage， inflammation and infiltration around the lumen， thickening of the trachea， and accumulation of edema fluid， and the SD medium dose group had the best effect on the treatment of PE. In terms of respiratory system， compared with the normal control group， the model group had reduced latent time of cough and asthma （P<0.05， P<0.01） and elevated number of cough and wheezing （P<0.01）. The three SD groups had increased latent time of cough and asthma and decreased number of cough and wheezing （P<0.01）. In terms of urinary system， compared with the normal control group， the model group presented decreased urine volume. The SD low， medium and high dose groups had increased urine volume （P<0.05， P<0.01）， but they had no effect on perspiration. In terms of digestive system， compared with the conditions in the normal control group， the gastric residual rate and gastrin （GT） level were increased （P<0.05， P<0.01）， and the gastric emptying rate and small intestine transit rate were decreased （P<0.01）. The SD low dose group had elevated small intestine transit rate （P<0.01）， and the SD high and medium groups had enhanced gastric emptying rate and small intestine transit rate （P<0.01）， reduced gastric residual rate， lowered GT level to promote gastrointestinal movement and transportation （P<0.01）， and increased motilin （MTL） level to promote gastric emptying in rats （P<0.05， P<0.01）. In terms of circulatory system， compared with the normal control group， the model group displayed reduced left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS） and cardiac output （CO） （P<0.01）， and elevated tendency of heart rate， systolic blood pressure （SBP， P<0.01） and diastolic blood pressure （DBP， P<0.05）. Compared with the model group， the SD low dose group increased LVEF and decreased DBP （P<0.05）， while the SD medium dose group increased LVEF， LVFS， CO and SBP （P<0.01） and decreased DBP （P<0.05）， and the SD high dose group increased LVFS （P<0.01） and decreased SBP （P<0.01） and DBP （P<0.05）. In terms of central nervous system， compared with the conditions in the normal control group， the standing times dropped in the model group （P<0.01）. SD reduced the movement distance， movement time， standing times and activity time in the center of the open field， and increased the rest time and activity time at the edge of the open field （P<0.05， P<0.01）. Moreover， compared with the normal control group， the model group had serious inflammatory infiltration around the lung lumen， thickened trachea with accumulated edema fluid， seriously damaged lung tissue， increased number of white blood cells and percentage of neutrophils in blood （P<0.01）， elevated percentage of monocytes， interleukin-4 （IL-4）， immunoglobulin E （IgE） level and reactive oxygen species （ROS） level in lung tissue （P<0.05，P<0.01）， and decreased IFN-γ in alveolar lavage fluid （P<0.01）. Compared with the model group， SD decreased the number of white blood cells， neutrophil accumulation， pulmonary congestion and interstitial edema， IFN-γ and IL-4 levels in alveolar lavage fluid and ROS level in lung tissue， and increased IgE level （P<0.05， P<0.01）. ConclusionSD had a significant improvement effect on PE model where the disease was located in the viscera. It could regulate the excretion of water by purgation， regulate Qi movement and expel Qi stagnation by descending and sinking lung Qi， and promote purification and descent of lung qi to make Qi movement downward. This indicated SD had the descending and sinking properties. The medium dose of SD decoction exerted the best effect， and its mechanism of action might be through regulating the neutrophil inflammatory response.
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OBJECTIVE To study the improvement effects of different polar parts fro m total f lavonoids of Scutellaria amoena on non-alcoholic fatty liver disease （NAFLD）model rats. METHODS The total flavonoids of S. amoena （SAF）were extracted by reflux extraction with ethanol ，suspended with water ，and then extracted with ethyl acetate and n-butanol in order to obtain the extraction parts of SAF （recorded as SAFA and SAFB respectively ）. Thirty-six rats were randomly divided into normal group （n＝ 6）and modeling group （n＝30）. Modeling group was given high-lipid diet to induce NAFLD model. After modeling ，modeling group was randomly divided into model group （normal saline ），fenofibrate group （positive control ，20 mg/kg），SAF group （300 mg/kg），SAFA group （300 mg/kg）and SAFB group （300 mg/kg）；they were given relevant intragastical administration ，once a day，for consecutive 6 weeks. After last administration ，the liver index was calculated ；the levels of total cholesterol （TC）， triacylglycerol（TG），aspartate transaminase （AST），alanine transaminase （ALT），high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C） in serum ，the levels of superoxide dismutase （SOD），glutathione peroxidase （GSH-Px），malondialdehyde（MDA），interleukin-1β（IL-1β），IL-6 and tumor necrosis factor-α（TNF-α）in liver tissue were detected；the pathomorphological changes of liver tissue were observed. RESULTS Compared with normal group ，the liver index ， the levels of TC ，TG，AST，ALT，LDL-C，MDA，IL-1β， IL-6 and TNF-α in serum/liver tissue of model group were all increased significantly （P＜0.05）， while the levels of HDL-C，SOD and GSH-Px were all decreased significantly （P＜0.05）. Compared with model group ，except there was no statistical significance in the serum levels of HDL-C and ALT in SAFA group （P＞0.05），above indexes in serum/liver tissue of rats in groups of polar parts from total flavonoids of S. amoena were significantly improved （P＜0.05）；inflammatory cell infiltration and fatty vacuoles in liver tissue were significantly improved. Compared with SAF group and SAFA group ，the levels of TC，TG，AST，MDA，IL-6 and TNF-α were decreased significantly in SAFB group（P＜0.05），while the level of SOD was increased significantly （P＜0.05）；pathomorphological changes of liver tissue were improved more significantly. CONCLUSIONS Each polar part from total flavonoids of S. amoena can improve NAFLD by regulating oxidative stress and inhibiting the secretion of inflammatory factors. The n-butanol polar part has more obvious effect .
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ObjectiveTo investigate the clinical characteristics of leprosy-related neuritis with bullous pemphigoid after treatment of paucibacillary leprosy. MethodsThe treatment of leprosy reaction combined with bullous pemphigoid of a cured case of leprosy was analysed. ResultsFive years after standard treatment for leprosy， erythema and vesicles appeared in the limbs without obvious inducement， and the disease became more and more severe. With clinical diagnosis and pathological examination， pemphigoid was confirmed， and the patients were given hormone treatment for leprosy reaction and anti-immunotherapy， as well as symptomatic supportive treatment. ConclusionLeprosy reaction and pemphigoid are both related to immunity， but the occurrence of both at the same time is relatively rare， so in the clinical process we should attach great importance to early detection， early diagnosis and prompt treatment to prevent further harm to the patient.
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OBJECTIVE To study the effects of ginsenoside Rb 1（G-Rb1）on epithelial-mesenchymal transition （EMT）of renal tubular epithelial cells and its potential mechanism. METHODS The growth factor β1（TGF-β1）10 ng/mL was used to induce EMT of human renal tubular epithelial cells HK- 2. The morphological changes of HK- 2 cells were observed after treated with 10， 20，30 μmol/L G-Rb1 for 48 h. The transcriptional activities of biovector SBE in human embryonic kidney cell HEK 293 were determined after 24 h treatment with 1.0，2.5，5.0，10，20，30 μmol/L G-Rb1. Effects of above concentration of G-Rb 1 on the viability of HK- 2 cells were determined after 24 h of treatment. mRNA expressions of α-smooth muscle actin （α-SMA），collagen Ⅰ （COL-Ⅰ）and fibronectin （FN）in HK- 2 cells were detected after treated with 10，20，30 μmol/L G-Rb1 for 24 h. The expressions of α-SMA，Smad3，p-Smad3，COL-Ⅰ，FN and E-cadherin were detected after treated with 10，20，30 μmol/L G-Rb1 for 24 h. RESULTS G-Rb1 of 10-30 μmol/L significantly inhibited TGF-β1-induced EMT in HK- 2 cells and the increase of transcriptional activities of biovector SBE induced by TGF-β1（P＜0.05），but had no effects on relative activities of HK- 2 cells（P＞0.05）. The protein and mRNA expressions of α-SMA，COL-Ⅰ and FN ， the protein expressions of Smad 3 and p-Smad 3 were significantly up-regulated induced by TGF-β1（P＜0.05），while the protein expression of E-cadherin was significantly down- regulated（P＜0.05）；G-Rb1 could effectively reverse aboveprotein or mRNA expressions. CONCLUSIONS G-Rb1 can protect renal tubular epithelial cells from EMT induced byxiezhishen TGF-β1 to a certain extent ，which may be related to inhibiting the activation of TGF-β1/Smad3 signaling pathway.
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Radiotherapy is still a major part of the program about treating various head and neck cancers. While improving the survival rate of head and neck cancer patients, radiotherapy can cause the decline of learning, memory, orientation and other functions, seriously, even lead to dementia, namely radiation induced cognitive dysfunction (RICD), which has become a critical factor affecting the quality of life for patients. Because of occult onset and unclear pathogenesis, so far there is few effective preventive and therapeutic tools for RICD. In this paper, the latest research progress on the pathogenesis and treatments of RICD is summarized.
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Objective:To discuss the effect of optimized catheter management strategy on reducing the incidence of catheter-related adverse events in interhospital patients transition with extracorporeal membrane oxygenation (ECMO).Methods:A historical control trial was conducted. The patients transferred with ECMO to the Second Affiliated Hospital of Nanchang University from January 2018 to December 2020 were enrolled. From January 2019 to December 2020, 38 patients with interhospital transport using optimized catheter management strategy were as observation group; from January to December in 2018, 30 patients with routine catheter management method were selected as the control group. The incidence of catheter-related adverse events during transition was compared between the two groups.Results:There were no significant differences in clinical data such as age, number of catheters, transit time, transit distance, ECMO operation time between the observation group and the control group [age (years old): 58.26±10.38 vs. 54.00±16.61, number of catheters (roots): 6.03±1.32 vs. 5.51±1.37, transit time (hours): 2.48±0.30 vs. 2.51±0.39, transfer distance (kilometers): 155.27±20.45 vs. 165.56±25.62, ECMO operating time (days): 8.47±1.28 vs. 9.11±1.99, all P > 0.05]. The incidence of catheter-related adverse events in the control group was 26.67% (8/30), among them, 2 patients had ECMO catheter discount after getting over the bed, causing the flow alarm; 1 patient's central venous catheter (CVC) was not placed with U-shape and twisted, the vasopressors were not entered in time, which caused hypotension; 3 patients had more bleeding at the puncture points and film crimping; the urinary catheters were clamped in 2 patients and not opened in time. In the observation group, the patients did not have catheter-related adverse events during transition. There was statistically significant difference in the incidence of catheter-related adverse events between the two groups (χ 2 = 7.814, P < 0.05). Conclusion:The implementation of optimized catheter management strategy can greatly reduce the incidence of catheter-related adverse events and provide an effective safety guarantee for the interhospital transit of ECMO patients.
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OBJECTIVE：To study the antioxidan t activity and lipid-lowering effect of ethanol extract and its different solvent extracts from the stems and leaves of Scutellaria amoena . METHODS ：The stem and leaves of S. amoena was extracted with 95％ ethanol to obtain ethanol extract ，and then extracted with petroleum ，ethyl acetate and n-butanol to obtain corresponding different solvent extracts. Using vitamin C （Vc）as positive control ，the antioxidant activities of ethanol extract ，petroleum ether extract ， ethyl acetate extract and n-butanol extract from the stems and leaves of S. amoena were determined by hydroxyl radical ，superoxide anion radical and DPPH radical scavenging method ，and the IC 50 was calculated. Steatosis L 02 hepatocyte model was established with fat emulsion. Using fenofibrate （20 μg/mL）as positive control ，the effects of high and low concentration （100 and 50 μg/mL） ethanol extract ，ethyl acetate extract and n-butanol extract from the stems and leaves of S. amoena on the contents of TC and TG in cells were investigated. RESULTS ：The order of scavenging ability to hydroxyl radicals was n-butanol extract ＞ethyl acetate extract＞Vc＞ethanol extract ＞petroleum ether extract ；IC50 of them were 0.15，0.17，0.35，0.75，1.17 mg/mL，respectively. The order of scavenging ability to superoxide anion radical was Vc ＞n-butanol extract ＞ethyl acetate extract ＞ethanol extract ＞ petroleum ether extract ；IC50 of them were 0.034，0.55，0.75，3.32，3.73 mg/mL，respectively. The order of DPPH scavenging ability to DPPH radical was Vc ＞n-butanol extract ＞ethyl acetate extract ＞ethanol extract ＞petroleum ether extract ；IC50 of them were 0.003 2，0.028，0.033，0.048，0.057 mg/mL， respectively. The ethanol extract ，ethyl acetate extract and n-butanol extract from the stems and leaves of S. amoena could significantly decrease the contents of TC and TG in steatosis L 02 hepatocytes （P＜0.01）. The order of lipid-lowering ability was n-butanol extract （low dose ）≈fenofibrate＞ethyl acetate extract （high dose ）＞ethanol extract （high dose ）＞ n-butanol extract （high dose ）＞ethyl acetate extract （low dose ）＞ethanol extract （low dose ）. CONCLUSIONS ：The ethanol extract ， petroleum ether extract ，ethyl acetate extract and n-butanol extract from the stems and leaves of S. amoena show good antioxidant activity and lipid-lowering effect （except for petroleum ether extract ）. Ethyl acetate extract and n-butanol extract possess the strongest antioxidant activity and lipid-lowering effect.
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Objective:To assess the radiosensitivity of polyvinylpyrrolidone (PVP) modified tantalum carbide (Ta 4C 3) nanosheets in human triple-negative breast cancer MDA-MB-231 cells in vitro. Methods:PVP-modified Ta 4C 3 nanosheets were synthesized and characterized. The uptake of fluoresceine isothiocyanate(FITC) labeled Ta 4C 3-PVP nanosheets in MDA-MB-231 cells was examined by fluorescent microscope. The toxicity of Ta 4C 3-PVP in the cells was measured by CCK-8 assay.These cells were divided into 4 groups: control group, Ta 4C 3-PVP group, irradiation group alone and Ta 4C 3-PVP plus irradiation group. The colony formation assay was used to evaluate the radiosensitivity. The levels of intracellular reactive oxygen species (ROS) and lipid oxidation production, malondialdehyde (MDA), were detected with an automatic microplate reader.γH2AX foci and mitotic catastrophe were observed by immunofluorescence staining. Results:Ta 4C 3-PVP nanosheets with a single-layer flaky shape were successfully synthesized. The hydrodynamic diameter and thick of Ta 4C 3-PVP nanosheets were about 143.93 nm and 1.35 nm, respectively. The FITC labeled Ta 4C 3-PVP nanosheets were uptaken by MDA-MB-231 cells, which was mainly distributed in the cytoplasm.Treatment of Ta 4C 3-PVP nanosheets at concentrations up to 400 μg/ml was noncytotoxic to MDA-MB-231 cells. The colony formation assay showed that pretreatment with Ta 4C 3-PVP at 50 and 100 μg/ml moved the survival curve of the irradiated cells downward in a concentration-dependent manner, compared to irradiation group alone. The sensitization enhancement ratio (SER D0 ) of Ta 4C 3-PVP at 50 and 100 μg/ml were 1.21 and 1.45, respectively.The intracellular ROS level in Ta 4C 3-PVP plus irradiation group was significantly higher than that in irradiation group alone at 2 and 12 h after irradiation ( q=20.01, 7.193, P<0.05). The percentage of positive cells with more than five γH2AX foci in Ta 4C 3-PVP plus irradiation group was higher than that of irradiation group alone at 1, 4 and 8 h after irradiation ( q=36.78, 14.87, 8.217, P<0.05). The content of MDA in Ta 4C 3-PVP plus irradiation group was significantly higher than that of irradiation group alone at 24 and 48 h after irradiation ( q=14.02, 7.015, P<0.05). The percentage of cells that succumbed to mitotic catastrophe in Ta 4C 3-PVP plus irradiation group was significantly higher than that in irradiation group alone at 72 h after irradiation ( q=16.33, P<0.05). Conclusions:Ta 4C 3-PVP nanosheets could enhance the radiosensitivity of human triple-negative breast cancer MDA-MB-231 cells through an increase of the intracellular ROS induced by irradiation.
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Objective:To compare the consistency and detection capability of seven 2019-nCoV nucleic acid detection kits, and provide reference for detection method selection of clinical laboratory and diagnosis of new coronavirus pneumonia.Methods:Two batches of pharyngeal swab samples were collected from tenpatients with confirmed infection of 2019-nCoV and 10 suspected patients with negative 2019-nCoV test results during January 29 to February 5, 2020 in Shenzhen Luohu People′s Hospital. Seven kinds of kits were labeled as ato g and used for nucleic acid detection respectively to evaluate the consistency of the test results of the clinical samples. A 2019-nCoV positive specimen was selected and diluted to 5-concentration gradient plates (Level-1 to 5) with RNase-free water. The positive detection rate and intra-batch repeatability of different brands of kits were compared.Results:The negative and positive coincidence rates of twenty clinical samples tested by six kinds of kits were 100%, and the positive and negative coincidence rate was 8/10 and 10/10 for the other kit, respectively. The results of intra-batch repeatability showed the CVs of viral loads tested by these seven kits were all less than 5%. In the concentration range of Level-1 to 3, the detection capability for open reading frame (ORF)1ab gene of Kit b,d and f was lower than Kit a,c,e and g, and the detection capability of kit e and g was the highest (14/15). The detection capability for N gene of Kit a (15/15) was higher than the other 5 kits. The comprehensive analysis of the detection capability for ORF1ab and N gene showedthat Kit d had the lowest detection capability (ORF1ab:40%,N:53%), and there was no significant difference in the detection capability of Kit a, b, c, e, and f.Conclusions:There was no significant difference in the accuracy and repeatability of the seven kits for positive samples with high viral loads, and the detection performance was good; but some kits had poor detection capability for weak positive samples. It is suggested that the weak positive samples should be rechecked by at least two manufacturers′ kits to ensure the accuracy of the results.