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Objective To observe the 24-week survival status of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) treated with plasma exchange (PE) and double plasma molecular adsorption system (DPMAS) alone or in combination, and to establish a predictive model for 24-week prognosis. Methods Related clinical data were collected from 133 patients with HBV-ACLF who received PE and DPMAS alone or in combination in The Affiliated Provincial Hospital of Anhui Medical University from January 2015 to December 2019, and according to the survival status at the 24-week follow-up after treatment, they were divided into survival group with 71 patients and death group with 62 patients. A total of 55 patients with HBV-ACLF who received PE and DPMAS alone or in combination in The Second Affiliated Hospital of Anhui Medical University from January 2018 to January 2020 were enrolled as validation group to validate the performance of the model. Related clinical data included mode of artificial liver support therapy, age, sex, total bilirubin (TBil), international normalized ratio (INR), creatinine (Cr), serum sodium, platelet count (PLT), albumin (Alb), and presence or absence of ascites, hepatorenal syndrome, hepatic encephalopathy, and gastrointestinal bleeding. The t -test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test and the Fisher's exact test were used for comparison of categorical data between groups. The Cox regression model was used to analyze the influencing factors for the prognosis of HBV-ACLF patients after PE and DPMAS alone or in combination and establish a predictive model; the receiver operator characteristic (ROC) curve was plotted and the DeLong method was used to compare the area under the ROC curve (AUC) between the new predictive model and Model for End-Stage Liver Disease (MELD)/MELD combined with serum sodium concentration (MELD-Na) scores. Results At 24 weeks after treatment, 71 patients survived and 62 patients died in the modeling group. The Cox regression analysis showed age (hazard ratio [ HR ]=1.030, P =0.013), TBil ( HR =1.018, P < 0.001), INR ( HR =1.517, P < 0.001), and PLT ( HR =0.993, P =0.04) were independent influencing factors for 24-week survival. According to the results of the Cox regression analysis, a prognostic model for HBV-ACLF patients treated with PE and DPMAS alone or in combination was established as ATIP=0.029×age (years)+0.018×TBil (mg/dL)+0.417×INR-0.007×PLT (10 9 /L). Both the modeling group and the validation group showed that the ATIP model had a better predictive performance than MELD and MELD-NA scores(all P < 0.05). Conclusion Age, TBil, INR, and PLT are independent influencing factors for the 24-week survival of HBV-ACLF patients treated with PE and DPMAS alone or in combination, and the ATIP model has a good performance in predicting the 24-week prognosis of HBV-ACLF patients treated with PE and DPMAS alone or in combination.
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Ferroptosis is an iron-dependent programmed cell death characterized by reactive oxygen species-induced lipid peroxide accumulation, which is different from cell apoptosis, pyroptosis, necrosis or autophagy. Ferroptosis plays an important role in the regulation of tumorigenesis and tumor development. Recent studies have shown that natural medicinal ingredients can induce ferroptosis in tumor cells through glutathione (GSH)/glutathione peroxidase 4 (GPx4) pathway, iron metabolism, lipid metabolism or other mechanisms. It has been reported that more than 30 natural medicinal ingredients can induce ferroptosis in tumor cells with multiple pathways and multiple targets. This article reviews the current research progress on the antitumor effects of natural medicinal ingredients through inducing cell ferroptosis.
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Humans , Apoptosis , Autophagy , Ferroptosis , Neoplasms/drug therapy , Reactive Oxygen SpeciesABSTRACT
Opioids are the main treatment drugs for the patients with moderate and severe cancer pain,and methadone is one of opioid drugs. Compared with the other opioids, methadone has the advantages of low cost, high oral bioavailability and better effect on neuropathic pain. However, methadone also shows such disadvantages as prolonged QT interval and large individual variance in pharmacokinetics. Although the safety of methadone has no difference from the other opioids in the treatment of cancer pain,the lack of knowledge and experience still limits its clinical application. This article aimed to summarize the clinical application of methadone in cancer patients,so as to help clinicians understand and apply methadone better.
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Objective: To investigate the utilization status of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in 11 hospitals of Zhejiang province from 2009 to 2015, and to analyze the use rationality.Methods: The doctor's advice in 40 days annually was collected in 11 hospitals of Zhejiang province from 2009 to 2015, and the drug consumption, frequency of utilization (DDDs), defined daily cost (DDC) and drug utilization index (DUI) were analyzed for the patients with lung cancer treated with EGFR-TKI.Results: Icotinib, erlotinib and gefitinib were the three prevalent EGFR-TKIs used in Zhejiang province, and icotinib started to be used in clinics in 2013.The overall cost of EGFR-TKIs increased year by year during 2009 and 2015, and the total amount of sales increased by 4.67 times in 2015 when compared with that in 2009.Generally, the DDDs value of erlotinib showed a decreasing trend, however, that of icotinib and gefitinib rose year by year during 2009 and 2015.Erlotinib had the highest DDC followed by gefitinib and icotinib.The mean value of DUI of the three targeted drugs was about 1.Conclusion: The utilization of EGFR-TKI is reasonable in 11 hospitals of Zhejiang province with increasing comsuption.
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OBJECTIVE:To provide reference for rational use of cancer pain narcotic drugs in our hospital. METHODS:The amount of narcotic drugs in our hospital was analyzed statistically during second quarter of 2012 to second quarter of 2015. RE-SULTS:12 specifications and 4 dosage forms of narcotic drugs were involved in our hospital during second quarter of 2012 to sec-ond quarter of 2015. Total amount of narcotic drugs was in an increasing tendency. Oxycodone hydrochloride sustained-release tablet was the largest quantity of narcotic drug used and grew fastest. The amount of surgical drugs kept stable,while total amount of oral preparation increased significantly,in particular,a significant increase in Morphine tablets. CONCLUSIONS:The application of narcotic drugs in our hospital is basically reasonable. The preferred oral principle has been implemented,and treatment of cancer pain is more standardized.
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OBJECTIVE:To investigate the status quo and tendency of endocrine therapy drugs in breast cancer patients from 11 hospitals of Zhejiang province during 2010-2015. METHODS:The prescriptions of breast cancer patients in 11 hospitals of Zhe-jiang province were analyzed retrospectively in respects of consumption sum,DDDs,DDC,etc. RESULTS:The consumption sum of endocrine therapy drugs in breast cancer patients from 11 hospitals of Zhejiang province during 2010-2015 increased from 2530192.33 yuan to 6201691.54 yuan,and its proportion in total consumption sum increased from 13.93％ to 17.40％,showing in-creasing tendency. The anastrozole always took up the first place in the list of consumption sum. Tamoxifen,anastrozole and letro-zole took up the top 3 places in the list of DDDs. Goserelin took up the first place in the list of DDC. CONCLUSIONS:The pre-scription amount and consumptionsum of endocrine therapy drugs in breast cancer patients from 11 hospitals of Zhejiang province during 2010-2015 show year-on-year growth trend;and those drugs which are safe,effective,economical and convenient predomi-nate in clinic.
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Objective To explore the efficacy of saxagliptin in the treatment of failed glycemic control of patients with type 2 diabetes mellitus on the basis of established treatments.Methods 172 cases of failed glycemic control of patients with type 2 diabetes mellitus from June 2013 to December 2014 in department of endocrinology of the first hospital of Ningbo were selected and received health education of 8 weeks, then received saxagliptin on the basis of established treatments for a consecutive treatment of 12 weeks.The HbA1c, fasting blood glucose ( FBG), 2-hours postprandial blood glucose (2hPBG), body mass index (BMI), insulin dosage and adverse event were observed.Results The FBG,HbA1c and 2hPBG after treatment of 12 weeks were significantly lower than those pre-treatment[(7.1 ±2.0)vs.(8.3 ±1.6)mmol/L,(10.2 ±2.3)vs.(15.2 ±2.9)mmol/L,(7.0 ±1.5) vs.(8.0 ±1.7)%], with significant difference (all P <0.05), while there was no significant difference in BMI between pre-and post-treatment [(24.4 ±3.0)vs.(24.9 ±2.7)kg/m2].The insulin dose after treatment of 12 weeks was significantly lower than that pre-treatment[(22.6 ±7.9)vs. (32.3 ±8.2) U/d], with significant difference (P <0.05).There were two patients dropout because of the intolerable digestive tract symptom. Conclusion The adding of saxagliptin could control FBG,2hPBG and HbA1c effectively and decrease insulin dose, without gaining weight in the treatment of failed glycemic control of patients with type 2 diabetes mellitus on the basis of established treatments.
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OBJECTIVE:To provide reference for rational use of leucocyte increasing drugs in patients with lung cancer. METHODS:The application of drugs in lung cancer patients in 40 d each year were collected from 11 Zhejiang hospitals during 2009-2014,and then analyzed retrospectively in consumption sum,DDDs,DDC and department distribution,etc. RESULTS:The proportion of consumption sum of leucocyte increasing drugs in total consumption sum decreased generally in 11 Zhejiang hospital during 2009-2014,decreasing from 781 995.50 yuan in 2009(3.28%)to 626 792.80 yuan in 2014(1.53%). Top 3 departments in the list of consumption sum of leucocyte increasing drugs were oncology department(29.00%),radiotherapy department(27.08%) and respiratory medicine department(9.93%). Top 3 drugs in the list of consumption sum during 2009-2014 were recombinant hu-man granulocyte colony-stimulating factor,Coenzyme complex for injection and Leucogen tablets;top 3 drugs in the list of DDDs were Leucogen tablets,Berbamine tablet and recombinant human granulocyte colony-stimulating factor;Coenzyme complex for in-jection,recombinant human granulocyte colony-stimulating factor and human GM-CSF took the first three place in the list of DDC during 2009-2013,and Leucogen tablets were the top one in 2014. CONCLUSIONS:The application of leucocyte increasing drugs in lung cancer patients is decreasing year by year in 11 Zhejiang hospitals,and those with definite therapeutic efficacy and moder-ate price predominate clinical application predominate in the clinical practive.
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Objective To investigate the self-assembly and cellular localization patterns of fila-mentous temperature-sensitive protein Z (FtsZ) in Escherichia coli (E.coli) strains by using FtsZP74R, FtsZG77D and FtsZA81R mutants.Methods YFP or His labeled FtsZ proteins and the plasmids of FtsZ mu-tants were constructed by using molecular clone and site-directed mutagenesis methods.The targeted proteins were purified by affinity chromatography.FL37(△ftsZ-Cat) strains were constructed via linear DNA homol-ogous recombination.Living cell imaging was performed to observe the cellular localization patterns of FtsZ protein and its mutants in E.coli strains.The interactions between FtsZ-FtsZ/FtsZ mutants were examined by coi-mmunoprecipitation assay . The polymerization properties of FtsZ mutants were analyzed by light scattering.The activities of GTPase were monitored by using high performance liquid chromatography.Re-sults The P74, G77 and A81 amino acids were respectively replaced by different polar amino acids to change the amphipathicity of the helix within the domain of FtsZ ( 74-82 ) .The YFP-labeled FtsZP74R , FtsZG77D and FtsZA81R mutants failed to assemble into functional Z-ring structure in E.coli strains.The inter-actions between FtsZ protein and its mutants were weakened or completely disappeared.In addition, in vitro experiments showed that P74R, G77D and A81R mutations caused a decrease in the polymerization efficien-cy of FtsZ monomer.The activity of GTPase was significantly decreased in the FtsZA81R mutant. Conclusion The P74, G77 and A81 were critical amino acids in the function and assembly of FtsZ protein in E.coli strains.Moreover, A81 amino acid regulated the lateral interaction of FtsZ monomer and the activity of GTPase.
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Objective:To explore the influence of chronic cobalt chloride (CoCl2 ) treatment on blood glucose and car-diomyocyte apoptosis in diabetic rats .Methods:In vivo MI model of rat was established using male GK diabetic rats and male Wistar rats (all weighing 200g~250g) .Blood glucose level was measured before model establishment .Af-ter successful operation ,rats were divided into six groups:Wistar sham operation group ,Wistar MI group ,Wistar MI + CoCl2 group ,GK sham operation group ,GK MI group and GK MI + CoCl2 group ,six rats survived in each group at least .After three weeks ,blood glucose level was measured and heart was excised ,expression of Caspase-3 apoptosis gene in ischemic necrosis area was measured .Results:(1) Compared with GK sham operation group and GK MI group on three weeks after operation ,there was significant reduction in blood glucose level [ (27.73 ± 2.58) mmol/L ,(27.87 ± 3.18) mmol/L vs .(16.3 ± 2.15) mmol/L] in GK MI + CoCl2 group ,P0.05 all .Conclusion:Chronic cobalt chloride treatment can decrease blood glucose level and reduce expression of Caspase-3 apoptosis gene in ischemic necrosis area in diabetic rats .
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Objective To explore the expression of interferon-inducible genes (IFIG) in idiopathic inflammatory myopathies (IIM) patients and its clinical significance.Methods Peripheral blood mononuclear cells from 52 IIM patients and 20 healthy controls were extracted.The transcriptional levels of six IFIG genes:oligoadenylate synthetase 1 (OAS-1),IFN-induced protein with tetratricopeptide repeats 1(IFIT1),IFIT4,interferon-inducible-protein 44 (IFI44),radical S-adenosyl methionine domain containing protein 2 (RSAD2) and myxo-virus resistance gene 1 (MX-1) were detected by real-time polymerase chain reaction (PCR).Interferon scores were calculated and compared.The correlations between interferon scores and clinical features of IIM patients were investigated.Non-parametric Mann-Whitney and Spearman analysis were used for statistical analysis.Results In IIM patients,the transcriptional levels of OAS-1 [90.4(40.2,350.8)],IFIT1 [112.7(49.8,151.1)],IFIT4 [127.8(110.4,200.2)],IFI44 [100.3(39.5,160.7)],RSAD2 [100.9(50.2,559.2)] and MX-1 [110.7(60.3,298.9)] were greatly higher than those in healthy controls [4.5(2.1,27.8),21.5(0.4,31.4)i 21.5(0.8,51.2),5.2(0.4,27.8),27.8(17.5,33.5),25.1(15.7,31.8),respectively] (Z=-5.121,-4.359,-5.301,-4.906,-4.348,-4.151; P＜0.01).Meanwhile,interferon scores were significantly elevated in IIM patients [65.7(3.6,136.9),Z=-5.778,P＜0.01],compared with healthy controls [1.2(0.1,3.1)],especially in those with interstitial lung disease [89.3(41.9,176.7),Z=0.544,P＜0.05].Interferon scores were correlated positively with ESR (r=0.234,P＜0.05).Conclusion The mRNA levels of OAS-1,IFIT1,IFIT4,IFI44,RSAD2 and MX-1 are significantly increased in patients with IIM.Interferon score might be used as a new biomarker for IIM patients.
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<p><b>OBJECTIVE</b>To compare the cytotoxic response with respect to different Shengmai injections manufactured by different manufacturers and to find the main reasons that cause the differences.</p><p><b>METHOD</b>L929 cells were cultured with various Shengmai injections which were incubated into serum-supplemented minimum essential medium at different doses. The cellular morphology was observed by phase contrast inverted microscopy and proliferation of the cells was examined using mitochondrial function methyl thiazolyl tetrazolium (MTT) assay. Relative growth rate (RGR) was calculated. Moreover, cytotoxicity was evaluated.</p><p><b>RESULT</b>For Shengmai injections manufactured by 8 manufacturers, cytotoxicity was high, Class 4. The EC value of sample A was high than other samples. This result indicated that sample A is much more toxic than other samples. For the excipients of Shengmai injections, when the concentration of tween 80 is 0.5% of composition of drug products, cytotoxicity was classified as 3-4; while the concentration of tween 80 is 0.062 5% of composition of drug products, the cellular toxicity was classified as 1 (no cellular toxic response). The content of tween 80 of shengmai injection is different during different factories; some of it is higher than 0.5%.</p><p><b>CONCLUSION</b>Cytotoxic results of these various injections were significantly different because of different manufacturers of drug substance and manufacturing process. As an excipient of injection, it showed cytotoxicity when the concentration is higher than 0.062 5%. The content of tween-80 and the degree of cytotoxicity in different Shengmai injections may have a positive correlation.</p>
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Animals , Mice , Cell Proliferation , Drugs, Chinese Herbal , Toxicity , Injections , Tetrazolium Salts , ThiazolesABSTRACT
Objective To investigate the effect and mechanism of different high concentrations glucose(Glu) on the expression of hypoxia-inducible factor 1α(HIF-1α) in cultured neonatal rat eardiomyocytes under hypoxia and non-hypoxia conditions. Methods Neonatal rat cardiomyocytes were cultured for 6 hours under different conditions and were divided into 6 groups:①Negative control group (5.5 mmol/L Glu) ; ②hypoxia mimicking cobalt chloride(Cocl_2) group(5.5 mmol/L Glu + 400 μmol/L cocl_2 ) ;③Different high concentrations Glu groups: (11.1 mmol/L, 22.2 mmol/L, 33.3 mmol/L Glu);④cocl_2 +different high concentrations Glu groups(11.1 mmol/L Glu +400 μmol/L cocl_2,22.2 mmol/L Glu +400 μmol/L cocl_2, 33.3 mmol/L Glu+400 μmol/L cocl_2);⑤High concentrations Glu + antioxidant α-tocopherol group(33.3 mmol/L Glu + 100 μmol/L α-tocopherol) ; ⑥ High concentrations Glu+antioxidant α-tocopherol+cocl_2 group(33.3 mmol/L Glu+400 μmol/L cocl_2+100 μmol/L α-tocopherol). The effect of high concentrations Glu, cocl_2 and high concentrations Glu plus cocl_2 on the expression of HIF- 1α mRNA and protein in cultured neonatal rat cardiomyocytes, as well as the effect of high concentrations Glu plus antioxidant α-tocopherol, high Glu concentrations plus cocl_2 and antioxidant α-tocopherol on the expression of HIF- 1α mRNA and protein were observed. Results 1. Compared with negative control group(5.5 mmol/L Glu), the 'expression of HIF- 1α was increased under cocl_2 mimicked hypoxia(5.5 mmol/L Glu+400 μmol/L cocl_2, 11.1 mmol/L Glu+400 μmol/L cocl_2 ,22.2 mmol/L Glu+400 μmol/L cocl_2,33.3 mmol/L Glu+400 μmol/L cocl_2). 2. The expression of HIF- 1α was increased gradually after the increasing of Glu concentrations(5.5 mmol/L, 11.1 mmol/L, 22.2 mmol/L and 33.3 mmol/L Glu).3.The expression of HIF-1α was decreased gradually after the increasing of Glu concentrations under certain cocl_2 plus different high concentrations Glu (5.5 mmol/L Glu+400 μmol/L cocl_2, 11.1 mmol/L Glu+400 μmol/L cocl_2, 22.2 mmol/L Glu+400 μmol/L cocl_2,33.3 mmol/L Glu+400 μmol/L cocl_2). 4. Under high concentration Glu plus antioxidant α-tocopherol (33.3 mmol/L Glu+100 μmol/L α-tocopherol) ,the expression of HIF- 1α was less increased than the same high Glu concentration(33.3 mmol/L Glu). 5. Under high Glu concentration plus cocl_2 (33.3 mmol/L Glu+400 μmol/L cocl_2), the expression of HIF- 1α increased less than that of the same high Glu concentration plus antioxidant α-tocopherol and cocl_2 (33.3 mmol/L Glu+400 μmol/L Cocl_2+ 100 μmol/L α-tocopherol). Conclusions High glucose increases the expression of HIF-1α under non-hypoxia, but blunts the expression of HIF-1α under hypoxia in cultured neonatal rat cardiomyocytes. Some mechanisms such as ROS (reactive oxygen species) signal transduction system and oxidative stress may be involved in it.
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[ Objective]To observe the curative effects on chronic diseases of respiratory system treated by “winter disease being cured in summer”.[Methods]One hundred and twenty-six patients with chronic diseases of respiratory system were treated by herbal medicine,points application of medicament,and ear points.All the patients were observed and reported after the treatment in detail.[Results]The total effective rate was 90.5%,and with satisfactory effect in long run.[Conclusion]It is reasonable to treat chonic diseases of respiratory system in this way.
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Objective To explore the effect of Jinkui Shenqi pill (JKSQP) on 17?-hydroxylase gene expression in kindney yang deficiency rats. Methods The rats were randomly divided into normal group, tmodel group and JKSQP group. Animal model of kidney yang deficiency was built by adenine. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to observe the effect of JKSQP on 17? -hydroxylase mRNA of adrenal tissue in rats treated at different time points (10, 20, 30 d). Results As compared with the model group, JKSQP can increase gene expression of 17?-hydroxylase in the adrenal of rats (P
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0.05). Conclusion All Nourishing Decoction can enhance the immunity of the body, inhibit the growth of tumor.
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Cardiomyocytes hypoxia resulting from ischemia is a major pathological factor in ischemic heart disease(IHD), and diabetes is one of the most common complications in IHD. myocardial damages aggravate and prognosis is worse in patients with coronary heart disease and diabetes, which is probably concerned with the reduction of hypoxia-inducible factor 1 (HIF-1) expression. But the mechanisms of HIF-1 signal transduction system in diabetes are not clear. In recent years, many studies have indicated that increasing expression and activity of HIF-1? in IHD can promote neovascularization and cardiomyocytes survival, decrease ischemical reperfusion injury and myocardial infarction (MI) size, and increase myocardial function. Therefore regulating expression and activity of HIF-1? becomes a new way to treat IHD. Myocardial infarction models were made in GK diabetes rats through the ligation of left anterior descending coronary artery (LADCA). By using immunohistochemistry staining and RT-PCR methods, results suggested that HIF-1? expression decreased and myocardial infarction size increased in GK diabetes rats combined with MI. When treated with cobalt chloride(CoCl2), blood glucose level decreased, HIF-1? expression increased and myocardial infarction size reduced in GK diabetes rats, which may provide a new insight on treatment of coronary heart disease combined with diabetes by regulating HIF-1 signal transduction system.
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[Objective]To explore the change of serum gastrin and G-cell in gastric antrum in rat model of spleen-qi deficiency and the curative effect of huangqi jianzhong decoction(HQJZD).[Methods]Spleen-qi deficiency syndrome was induced in rats by compound methods.After the models had been established,they were treated by different dosages of HQJZD.And at different time points,serum xylose,creatine phosphokinase,gastrin and G cells were observed.[Results]These indexes in groups of different dosages of HQJZD recovered gradually.Especially after 21 days' treatment,in groups of the middle and the high dosages,these indexes were increasing significantly when compared with those in the model control group(P
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Hanzhihe was the first physician who elucidated the academic thoughts of Treatise on Cold Pathogenic Diseases(Shanghan Lun) during of the Northern Song Dynasty(960-1127).His ideas were involved four aspects.He interpreted the pathogenesis of cold pathogenic diseases,explaining the six meridians by channels and collaterals;paid attention to the syndrome differentiation of pulse tracings and discussed the rules of diaphoresis and purgation;preferred the therapeutic method of warming the middle jiao firstly,taking the medicine by the seasonal disposition;replenished the syndrome differentiation and treatment of stagnated blood syndrome,and originated the effective formula of the Yin jaundice therapy.
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Objective: To explore the effect of buzhong yiqi decoction(BZYQD) with various concentrations at different time points on gastrin(GAS) gene expression level in spleen-qi deficiency rats.Methods: The spleen-qi deficiency rats were randomly divided into the model control group and the low,medium and high dosage of BZYQD groups.Reverse transcriptase polymerase chain reaction was used to observe the effect of BZYQD on the GAS mRNA of gastric antrum in rats treated at different time points(7,14,21d).Results: As compared with that in model control group,the GAS gene expression level were significantly higher both in the medium and high dosage groups(P