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1.
Clin Sci (Lond) ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922199

RESUMO

Acute myeloid leukemia (AML) is a malignant disorder of haemopoietic stem cells. AML can escape immunosurveillance of natural killer (NK) by gene mutation, fusions and epigenetic modification. The mechanism of AML immune evasion is not clearly understood. Here we show that CD48 high expression is a favorable prognosis factor that is downregulated in AML patients, which can help AML evade from NK cell recognition and killing. Furthermore, we demonstrate that CD48 expression is regulated by methylation and that a hypomethylating agent can increase the CD48 expression, which increases the NK cells killing in vitro. Finally, we show that CD48 high expression can reverse the AML immune evasion and activate NK cells function in vivo. This study suggests that a combination the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.

2.
Res Vet Sci ; 128: 308-314, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901569

RESUMO

As most pathogens invade the bodies through the mucosa, it is crucial to develop vaccines that induce mucosal immunity. To this end, we generated a safe and effective vaccine candidate that displayed fimbrial protein 987P of enterotoxigenic Escherichia coli (ETEC) on the surface of Lactobacillus casei (L.casei) CICC 6105 by using poly-γ-glutamate synthetase A (PgsA) as an anchoring matrix. After gavage inoculation of the recombinant strain pLA-987P/L.casei into specific-pathogen-free (SPF) BALB/c mice, high levels of mucosal immunoglobulin A (IgA) were induced in fecal samples, intestine and lung lavage fluids and systemic immunoglobulin G of IgG subclasses (IgG1, IgG2b, and IgG2a) was produced in serum. T-cell proliferation assays showed the stimulation index (SI) of the groups immunized with pLA-987P/L.casei to be significantly higher than that of the control group. The recombinant L.casei promoted T cells to produce both Th1 and Th2 cytokines, while the number of splenic IL-4 Spot forming cells (SFC) exceeded the number of IFN-γ SFC by 2.26-fold (P < .01). >83.3% of the vaccinated mice were protected from challenge with a lethal dose of virulent strain C83916. These results indicate that the recombinant L.casei expressing ETEC 987P fimbrial protein could elicit a protective immune response against ETEC 987P infection effectively.

3.
Genes Brain Behav ; : e12639, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925923

RESUMO

Schizophrenia and substance involvement frequently co-occur in individuals, and a bidirectional relationship between the two has been proposed; shared underlying genetic factors could be an alternative explanation. This study investigated the genetic overlap between schizophrenia and substance involvement, including tobacco, alcohol, and betel nut use. The study subjects were recruited from the Taiwan Biobank, and genome-wide genotyping data was available for 18 327 participants without schizophrenia. We calculated the Psychiatric Genomics Consortium-derived polygenic risk score (PRS) for schizophrenia in each participant. The significance of the schizophrenia PRS associated with substance involvement was evaluated using a regression model with adjustments for gender, age, and population stratification components. The modified effect of gender or birth decade was also explored. The schizophrenia PRS was positively associated with lifetime tobacco smoking in women (OR in per SD increase in PRS = 1.12 with 95% CI 1.04-1.20, P = 0.002), but not in men (OR = 0.99 with 95% CI 0.95-1.04, P = 0.74), and the gender-PRS interaction reached significance (P = 0.006). The OR between PRS and lifetime tobacco smoking increased with the birth decade (p of birth decade-PRS interaction = 0.0002). In women, OR increased from 0.97 (P = 0.85) for subjects with a birth decade before 1950 to 1.21 (P = 0.04) for subjects with a birth decade after 1980; in men, the corresponding OR increased from 0.88 (P = 0.04) to 1.13 (P = 0.11). There was no association between schizophrenia PRS and alcohol/betel nut use phenotypes. This study provides evidence for the genetic overlap between schizophrenia and tobacco use in women, and this overlap was stronger in the younger population. This article is protected by copyright. All rights reserved.

4.
FASEB J ; 34(1): 1319-1330, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914610

RESUMO

Posttranslational modifications enhance the functional diversity of the proteome by modifying the substrates. The UFM1 cascade is a novel ubiquitin-like modification system. The mutations in UFM1, its E1 (UBA5) and E2 (UFC1), have been identified in patients with microcephaly. However, its pathological mechanisms remain unclear. Herein, we observed the disruption of the UFM1 cascade in Drosophila neuroblasts (NBs) decreased the number of NBs, leading to a smaller brain size. The lack of ufmylation in NBs resulted in an increased mitotic index and an extended G2/M phase, indicating a defect in mitotic progression. In addition, live imaging of the embryos revealed an impaired E3 ligase (Ufl1) function resulted in premature entry into mitosis and failed cellularization. Even worse, the embryonic lethality occurred as early as within the first few mitotic cycles following the depletion of Ufm1. Knockdown of ufmylation in the fixed embryos exhibited severe phenotypes, including detached centrosomes, defective microtubules, and DNA bridge. Furthermore, we observed that the UFM1 cascade could alter the level of phosphorylation on tyrosine-15 of CDK1 (pY15-CDK1), which is a negative regulator of the G2 to M transition. These findings yield unambiguous evidence suggesting that the UFM1 cascade is a microcephaly-causing factor that regulates the progression of the cell cycle at mitosis phase entry.

6.
Leuk Lymphoma ; : 1-10, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31916883

RESUMO

The prognostic significance of loss of X chromosome (-X) in t(8;21) acute myeloid leukemia (AML) remains unclear. We evaluated the role of -X in 158 female patients with t(8;21) AML collected retrospectively from 15 Chinese AML study groups. Patients with -X accounted for 25.3% and showed a significantly higher complete remission rate, better 3-year cumulative incidence of relapse (25.2 vs. 50.5%, p = 0.013), relapse-free survival (69.4 vs. 44.7%, p = 0.025), and overall survival (77.4 vs. 52.7%, p = 0.026) compared with those without -X. Patients with -X were more likely to achieve minimal residual disease negativity (risk ratio = 1.62; p = 0.020). A Multivariate analysis adjusting for age, white blood cell, KIT-D816 mutation, high-dose cytarabine consolidation therapy, and allogeneic hematopoietic stem-cell transplantation showed -X to be an independent favorable prognostic factor. Our results suggest that -X may be associated with better outcomes in patients with t(8;21) AML.

7.
J Hum Genet ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31907389

RESUMO

Delta opioid receptor (DOR) is well known to be involved in heroin dependence. This study tested the hypothesis that single nucleotide polymorphisms (SNPs) in the opioid receptor delta 1 (OPRD1) gene coding region are associated with treatment responses in a methadone maintenance therapy (MMT) cohort in Taiwan. Three hundred forty-four MMT patients were recruited. Diastolic/systolic blood pressure, heart rate, methadone dosage, and plasma concentrations of methadone were recorded. Twenty-five SNPs located within the OPRD1 genetic region were selected and genotyped from the genomic DNA of all 344 participants. After pairwise tagger analyses, tagger SNP rs204047 showed a significant association with methadone dosage (P = 0.0019), and tagger SNPs rs204047 and rs797397 were significantly associated with plasma R, S-methadone concentrations (P < 0.0006) in patients tested negative in the urine morphine test, which indicated patients with a better response to MMT. The major genotype carriers showed a higher methadone dosage and higher plasma concentrations of R, S-methadone than the minor genotype carriers. The results indicated that OPRD1 genetic variants were associated with methadone dosage and methadone plasma concentration in MMT patients with a negative morphine test result.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31900519

RESUMO

A new highly specific high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method coupled to microdialysis sampling was developed and validated for simultaneous determination of L-ephedrine, D-pseudoephedrine, L-methyl-ephedrine, cinnamic acid, liquiritin, amygdalin, and glycyrrhizic acid both in rat blood and brain after oral administration of Mahuang decoction in this paper. An Agilent Zorbax SB-C18 using the 0.1% formic acid water solution and acetonitrile as mobile phase with a gradient elution was applied to the chromatographic separation. The ion transitions were quantified in positive mode for D-pseudoephedrine, L-ephedrine, L-methylephedrine, and diphenhydramine (internal standard), while negative mode for liquiritin, glycyrrhizic acid, amygdalin, cinnamic acid, and prednisolone (internal standard). Several parameters of the method including linearity, accuracy, precision, stability, and matrix effect were within acceptable ranges. The results showed the LC-MS/MS method coupled to microdialysis sampling can be utilized for the pharmacokinetic studies of these seven ingredients in vivo. According to the pharmacokinetic results, the pharmacokinetic parameters of L-ephedrine, D-pseudoephedrine, L-methylephedrine, glycyrrhizic acid, cinnamic acid, liquiritin, and amygdalin were totally different in rat blood and brain, the bioavailability of ephedrine and amygdalin in the blood and brain was higher, while the MRT of ephedrine was the shortest. In the rat brain, the elimination rate of three Ephedra alkaloids was lower than that of the remaining four components. This research offered more basic pharmacokinetic information on the safety mechanisms of Mahuang decoction.

9.
J Food Drug Anal ; 28(1): 115-123, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31883599

RESUMO

Tumor cell-induced platelet aggregation (TCIPA) is a mechanism that involves the protection of tumor cells in the circulation and the promotion of tumor cell invasion and metastases. The C-type lectin-like receptor 2 (CLEC-2) that binds podoplanin (PDPN) is on the platelet surface and facilitates the TCIPA. Selective blockage of the PDPN-mediated platelet-tumor cell interaction is thereby a plausible strategy for inhibiting metastases. In a search for antagonists of PDPN- and tumor cell-induced platelet aggregation, traditional Chinese medicines were screened and it was found that the water extract of Artemisia argyi leaves selectively inhibited the PDPN-induced platelet aggregation. Bioactivity-guided fractionation analysis was performed for defining a polysaccharide-containing fraction (AAWAP) characterized by inhibition of PDPN activity and tumor cell-induced platelet aggregation. The pharmacological effects of AAWAP on PDPN-activated CLEC-2 signaling were determined by using Western blot and alpha screening analyses. AAWAP was non-toxic to the cells and platelets and it suppressed PDPN- and tumor cell-induced platelet aggregation by irreversibly blocking the interaction between PDPN and CLEC-2 in a dose-dependent manner. These findings indicate that AAWAP is an antagonist of the PDPN-CLEC-2 interaction. This action by AAWAP may result in the prevention of tumor cell metastases, and if so, could become an effective pharmacological agent in treating cancer patients.

10.
Arch Insect Biochem Physiol ; 103(1): e21626, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562754

RESUMO

Insects can produce various antimicrobial peptides (AMPs) upon immune stimulation. One class of AMPs are characterized by their high proline content in certain fragments. They are generally called proline-rich antimicrobial peptides (PrAMPs). We previously reported the characterization of Spodoptera litura lebocin-1 (SlLeb-1), a PrAMP proprotein. Preliminary studies with synthetic polypeptides showed that among the four deductive active fragments, the C-terminal fragment SlLeb-1 (124-158) showed strong antibacterial activities. Here, we further characterized the antibacterial and antifungal activities of 124-158 and its four subfragments: 124-155, 124-149, 127-158, and 135-158. Only 124-158 and 127-158 could agglutinate bacteria, while 124-158 and four subfragments all could agglutinate Beauveria bassiana spores. Confocal microscopy showed that fluorescent peptides were located on the microbial surface. Fragment 135-158 lost activity completely against Escherichia coli and Staphylococcus aureus, and partially against Bacillus subtilis. Only 124-149 showed low activity against Serratia marcescens. Negative staining, transmission, and scanning electron microscopy of 124-158 treated bacteria showed different morphologies. Flow cytometry analysis of S. aureus showed that 124-158 and four subfragments changed bacterial subpopulations and caused an increase of DNA content. These results indicate that active fragments of SlLeb-1 may have diverse antimicrobial effects against different microbes. This study may provide an insight into the development of novel antimicrobial agents.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Insetos/farmacologia , Spodoptera/química , Animais , Peptídeos Catiônicos Antimicrobianos/química , Bacillus subtilis/efeitos dos fármacos , Beauveria/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Proteínas de Insetos/química , Serratia marcescens/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
11.
Bioresour Technol ; 296: 122290, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31677404

RESUMO

Three-dimensional biofilm electrode reactors (3D-BERs) with high treatment efficiency were constructed to treat wastewater containing sulfadiazine (SDZ) and ciprofloxacin (CIP) coexposure with Zinc (Zn). The results showed that coexposure to target antibiotics and Zn increased the absolute and relative abundances of target antibiotic resistance genes (ARGs). Additionally, the target ARG abundances were higher on cathode of 3D-BER compared with ordinary anaerobic reactor while the abundances of total ARGs were decreased in the effluent. Meanwhile, redundancy analysis results revealed that the composition of bacteria carrying ARGs was greatly influenced in the cathode by the accumulation of Zn and antibiotic, which dominated the changes of ARG abundances. Additionally, ARGs with their host bacteria revealed by network analysis were partially deposited on electrode substrates when being removed from wastewater. Thus, 3D-BER exhibits capability of simultaneously eliminating antibiotic and Zn, and greatly reduces the risks of ARGs spread.


Assuntos
Antibacterianos , Ciprofloxacino , Bactérias , Biofilmes , Resistência Microbiana a Medicamentos , Eletrodos , Genes Bacterianos , Características de Residência , Sulfadiazina , Águas Residuárias , Zinco
12.
Bioresour Technol ; 296: 122352, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31708385

RESUMO

The aim of this work was to study reverse solute flux (RSF) from osmotic membrane bioreactor (OMBR) and consequent solute buildup in the feed side. A polyelectrolyte (PAA-Na) served as a draw solute (DS) to minimize RSF in OMBRs. In addition, a bioelectrochemical system (BES) was employed to drive accumulated cations from the feed/anode side into the cathode compartment, subsequently achieving PAA-Na DS recovery with the aid of high catholyte pH. Compared to the 1 M NH4HCO3 DS, the 0.48 g mL-1 PAA-Na DS produced consistently stable water flux, enhanced water recovery and increased ammonium removal efficiency. Due to a dynamic balance between PAA removal and continuing RSF, the residual PAA concentration was 72 mg L-1 on the feed side (27.0% of TOC). These results demonstrate the advantages of integrating a PAA-Na DS with a BES to mitigate RSF and to support further development of OMBR technology.


Assuntos
Polieletrólitos , Purificação da Água , Reatores Biológicos , Membranas , Membranas Artificiais , Osmose
13.
In Vivo ; 34(1): 469-478, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882515

RESUMO

Background/Aim: Whole-body positron-emission tomography/computed tomography with the glucose analog 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG-PET/CT) has been used to screen examinees for underlying malignancy in many countries. The aim of this study was to compare the potential value of FDG-PET/CT application in asymptomatic individuals with those with suspected malignancy. Patients and Methods: A total of 9,408 examinees underwent whole-body FDG-PET/CT at our hospital from July 2006 to August 2013. Three thousand and seven hundred asymptomatic individuals and 848 individuals with laboratory and clinical/radiologicaI suspicion of malignancy who had undergone FDG-PET/CT for cancer screening were recruited. The final confirmation of cancer and outcomes were based on a pathological report and continuous follow-up. Results: Forty-five out of 3,700 asymptomatic individuals (1.2%) had proven malignancy, and 42 of them (93.3%) were found by FDG-PET/CT. Two hundred and twelve out of 848 with suspected malignancy (25%) had proven malignancy, and 196 of them (92.5%) were detected by FDG-PET/CT. Most of these cancers in asymptomatic individuals were clinically at an early stage. The discovery rate in asymptomatic individuals and those with suspected malignancy was 1.1% and 23.1%, respectively. The overall survival of patients with cancer diagnosed with PET/CT was higher than those with suspected malignancy (78.6% vs. 48.5%, p<0.001). Patients with a resectable lesion, early-stage disease, and lower maximal standardized uptake value had significantly better survival than those without. Conclusion: FDG-PET/CT is useful in the early diagnosis of cancer and thus might improve the survival rates of these patients. Considering the costs and risk of radiation exposure, it would be better used as a priority in patients with laboratory and clinical/radiologic suspicion of malignancy.

14.
Hemodial Int ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804777

RESUMO

INTRODUCTION: Leptin is an adipokine secreted from adipocytes that mediate lipid metabolism and inflammation. This cross-sectional study investigated the relationship between serum leptin level and nutrition status evaluated by malnutrition-inflammation score (MIS) among patients undergoing hemodialysis (HD). METHODS: This study included 100 patients on HD. Nutritional status was based on MIS (malnutrition ≥7 points). Body composition, biochemistry data, and serum leptin level were evaluated. FINDINGS: Of 100 subjects, 33 (33.0%) were categorized as having malnutrition. Compared with subjects in the well-nourished group, those in the malnutrition group had on average an older age, longer HD duration, and lower height, weight, body mass index, waist circumference, body fat mass, serum triglyceride level, and creatinine level. Serum leptin levels were also significantly lower in the malnutrition group (P < 0.001), whereas C-reactive protein (CRP) levels were higher (P = 0.002). Multivariable linear regression analysis revealed that HD duration (ß = 2.06, P = 0.009), serum leptin level (ß = -5.16, P < 0.001), CRP level (ß = 3.33, P < 0.001), and albumin level (ß = -1.95, P = 0.008) were factors independently associated with MIS. The discriminative power of serum leptin level to predict malnutrition was 0.834 (95% confidence interval: 0.747-0.901, P < 0.001). DISCUSSION: Low serum leptin level was associated with malnutrition, and serum leptin level may be a valuable marker for nutrition assessment in patients undergoing HD.

15.
Sci Total Environ ; : 135096, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31806312

RESUMO

Cadmium (Cd) is one of the most hazardous trace metals, and rapeseed is a major oil crop over the world with considerable lignocellulose residues applicable for trace metal phytoremediation and cellulosic ethanol co-production. In this study, we examined that two distinct rapeseed cultivars could accumulate Cd at 72.48 and 43.70 ug/g dry stalk, being the highest Cd accumulation among all major agricultural food crops as previously reported. The Cd accumulation significantly increased pectin deposition as a major factor for trace metal association with lignocellulose. Meanwhile, the Cd-accumulated rapeseed stalks contained much reduced wall polymers (hemicellulose, lignin) and cellulose degree of polymerization, leading to improved lignocellulose enzymatic hydrolysis. Notably, three optimal chemical pretreatments were performed for enhanced biomass enzymatic saccharification and bioethanol production by significantly increasing cellulose accessibility and lignocellulose porosity, along with a complete Cd release for collection and recycling. Hence, this study proposed a mechanism model interpreting why rapeseed stalks are able to accumulate much Cd and how the Cd-accumulated stalks are of enhanced biomass saccharification. It has also provided a powerful technology for both cost-effective Cd phytoremediation and value-added bioethanol co-production with minimum waste release.

16.
BMC Plant Biol ; 19(1): 545, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818257

RESUMO

BACKGROUND: Carica papaya is a trioecious plant species with a genetic sex-determination system defined by sex chromosomes. Under unfavorable environmental conditions male and hermaphrodite exhibit sex-reversal. Previous genomic research revealed few candidate genes for sex differentiation in this species. Nevertheless, more analysis is still needed to identify the mechanism responsible for sex flower organ development in papaya. RESULTS: The aim of this study was to identify differentially expressed genes among male, female and hermaphrodite flowers in papaya during early (pre-meiosis) and later (post-meiosis) stages of flower development. RNA-seq was used to evaluate the expression of differentially expressed genes and RT-qPCR was used to verify the results. Putative functions of these genes were analyzed based on their homology with orthologs in other plant species and their expression patterns. We identified a Male Sterility 1 gene (CpMS1) highly up-regulated in male and hermaphrodite flower buds compared to female flower buds, which expresses in small male flower buds (3-8 mm), and that might be playing an important role in male flower organ development due to its homology to MS1 genes previously identified in other plants. This is the first study in which the sex-biased expression of genes related to tapetum development in the anther developmental pathway is being reported in papaya. Besides important transcription factors related to flower organ development and flowering time regulation, we identified differential expression of genes that are known to participate in ABA, ROS and auxin signaling pathways (ABA-8-hydroxylases, AIL5, UPBEAT 1, VAN3-binding protein). CONCLUSIONS: CpMS1 was expressed in papaya male and hermaphrodite flowers at early stages, suggesting that this gene might participate in male flower organ development processes, nevertheless, this gene cannot be considered a sex-determination gene. Due to its homology with other plant MS1 proteins and its expression pattern, we hypothesize that this gene participates in anther development processes, like tapetum and pollen development, downstream gender specification. Further gene functional characterization studies in papaya are required to confirm this hypothesis. The role of ABA and ROS signaling pathways in papaya flower development needs to be further explored as well.

17.
Ann Hematol ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828376

RESUMO

The optimal rabbit anti-thymocyte globulin (rATG) graft-versus-host disease (GVHD) prophylaxis regimen in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT) remains to be elucidated. In this prospective study, we used low-dose rATG for GVHD prophylaxis in patients or donors aged ≥ 40 years with hematological malignancies receiving MSD-PBSCT. rATG was administered to 40 patients at an intravenous dose of 5 mg/kg divided over day 5 and day 4 before graft infusion. No graft failure occurred. Median times to leukocyte engraftment and platelet engraftment were 11.0 days and 13.9 days. The cumulative incidence of grades 2-4 and grades 3-4 acute GVHD at day +100 was 30.0% and 2.6%. The 2-year cumulative incidence of extensive chronic GVHD and severe chronic GVHD was 11.4% and 14.7%. 93.5% (29/31) of patients had discontinued immunosuppressive medication within 3 years after transplantation. The 2-year cumulative incidence of transplant-related mortality (TRM) and relapse was 14.0% and 22.6%. The cumulative incidence of cytomegalovirus reactivation, Epstein-Barr virus reactivation, and fungal infection was 22.3%, 12.9%, and 12.5%. Kaplan-Meier estimates for overall survival, disease-free survival, and GVHD-free and relapse-free survival 3 years after transplantation were 68.9%, 68.9%, and 54.0%. rATG for GVHD prophylaxis is tolerable and efficacious at a 5 mg/kg total dose administered over 2 days (days -5 to -4) in patients receiving allogeneic MSD-PBSCT.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31828667

RESUMO

BACKGROUND AND OBJECTIVE: Dan-Hong injection, which comprises extracts of Salvia miltiorrhiza and Carthamus tinctorius, promotes blood circulation and reduces blood stasis. Combination of S. miltiorrhiza and C. tinctorius is more effective in treating cerebral ischemia than S. miltiorrhiza alone. This study aimed to examine the pharmacokinetic characteristics of four active ingredients of S. miltiorrhiza and C. tinctorius, namely danshensu (DSS), hydroxysafflor yellow A (HSYA), and salvianolic acid A (SAA) and B (SAB) in normal and cerebral ischemia rats. METHODS: Normal and cerebral ischemia rats were injected via the tail vein with each active ingredient, and blood was collected through the jaw vein at different time points. The plasma concentration of the compatibility group was analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using Pharmacokinetic Kinetica 4.4 software. RESULTS: The pharmacokinetics of the four active ingredients in the normal and cerebral ischemia rats were consistent with a two-compartment model. The area under the concentration-time curve was higher in normal rats than in cerebral ischemia rats, with a highly significant difference for SAA (P < 0.01). Clearance rates were lower in normal rats than in cerebral ischemia rats, with DSS showing the most significant difference (P < 0.01). Furthermore, there were significant differences between normal and cerebral ischemia rats in the distribution phase-elimination half life for DSS, SAA, and HSYA, as well as in the apparent volume of distribution for the central compartment for DSS and HSYA (P < 0.01). The plasma concentrations of the four active ingredients were higher in normal rats than in cerebral ischemia rats. CONCLUSION: Cerebral ischemia rats showed higher drug clearance rates and longer retention times than normal rats, which may be due to destruction of the blood-brain barrier during cerebral ischemia-reperfusion. The four active ingredients likely integrated and interacted with each other to affect target sites in the brain to protect against cerebral ischemic injury.

19.
Oncology ; : 1-8, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31794969

RESUMO

OBJECTIVES: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC. METHODS: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis. RESULTS: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84-5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11-3.65, p = 0.02) were independent prognostic factors. CONCLUSION: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.

20.
Exp Ther Med ; 18(6): 4583-4590, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31798698

RESUMO

This study aimed to explore the improvement of hip replacement combined with alendronate sodium on the condition of patients with osteoporotic femoral neck fracture and factors affecting the efficacy of patients. In total, 140 patients with femoral neck fracture from July 2015 to October 2017 in the Affiliated Xuzhou Hospital of Jiangsu University were collected. Of these, 61 patients were treated with hip replacement as the control group and 79 patients were treated with alendronate sodium as the observation group on the basis of the control group. ELISA was used to detect levels of carboxy-terminal opeptide of type I collagen (CTX-I) and bone alkaline phosphatase (BALP) in serum of patients before and after treatment. Harris score was used to compare the clinical efficacy of patients after treatment. Changes in the expression of CTX-I and BALP before and after treatment were compared between the two groups, and the correlation between CTX-I and BALP levels and Harris score was analyzed. According to the clinical efficacy of patients, the two groups were divided into the significant effect group and poor effect group. Risk factors affecting the efficacy of patients were analyzed, and the ROC of subjects with risk factors was drawn. After treatment, the expression of BALP in serum increased significantly compared with that before treatment, and the expression of CTX-I decreased significantly. After treatment, the expression of BALP in serum in the observation group was significantly higher than that in the control group (P<0.05). Multivariate analysis revealed that age, time of operation, CTX-I after treatment and BALP after treatment were independent risk factors affecting the efficacy of patients. In conclusion, hip replacement combined with alendronate sodium can effectively improve the clinical efficacy of patients, and age, time of operation, CTX-I after treatment and BALP after treatment are found to be independent risk factors affecting the postoperative efficacy of patients.

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