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Purpose@#Nurses play an important role in ensuring patient rehabilitation and are involved in all aspects of multidimensional rehabilitation.Therefore, strengthening rehabilitation nursing education is vital to ascertain high-quality rehabilitation and optimum outcomes. This study examined the effectiveness of a new teaching reform—a modified Six-Sigma-based training program—against a conventional educational program on rehabilitation specialist nurses’ core competencies, post-training performance, and satisfaction. @*Methods@#A quasi-randomized controlled trial was conducted to assess the effectiveness of the modified training program. We recruited 56 learners from the 2020 training course at the Hunan Rehabilitation Specialist Nurse Training Base as the control group. Sixty learners from the base’s 2021 training course were recruited as the intervention group. Data were collected in a consistent manner from both groups after the training program was implemented. @*Results@#Those who underwent the modified training program showed better improvement in all core competencies than those who underwent the conventional training program (p < .05); the scores for theoretical knowledge, clinical nursing lectures, reviews, and nursing case management improved significantly following the teaching reform (p < 0.05). Further, overall satisfaction as well as base management and theoretical teaching satisfaction improved significantly (p < .05). @*Conclusion@#The modified training program strengthens rehabilitation nurses’ base management abilities; enhances their core competencies; expands their interest in and breadth, depth, and practicability of theoretical courses; and updates the teaching methods.
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Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.
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Adulto , Adolescente , Humanos , Prognóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Estudos Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T , Doadores não RelacionadosRESUMO
Objective: To develop asolvent extraction-direct mercury analyzer method for determination of methylmercury in urine. Methods: After the urinehydrolyzesd by hydrobromic acid, methylmercury was extracted by tolueneand reverse-extracted from L-cysteine solution, it was then detectedbydirect mercuryanalyzer. Results: The linear range was 0.2-50.0 μg/L, and the related coefficient was 0.9999. The relative standard deviations (RSD) within the group were 5.04%-6.64%, and the RSD between the group were 5.65%-8.11 %. The average recovery efficiencies were 85.4%-95.5%. The detection limitation was 0.0482 μg/L and the quantification concentrations was 0.1607 μg/L. Conclusion: The method, which has low detection limit, high sensitivity, easy to operate, is stability for the determination of methylmercury in urine.
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Mercúrio , Compostos de MetilmercúrioRESUMO
This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 μmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.
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Osteogênese , Subunidade alfa 1 de Fator de Ligação ao Core/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cálcio/metabolismo , Diferenciação Celular , RNA Mensageiro/metabolismo , Proliferação de Células , OsteoblastosRESUMO
ObjectiveTo investigate the effect of xenon post-conditioning on autophagy after spinal cord ischemia/reperfusion injury (SCIRI) in rats and its relationship with protein kinase B (Akt) signaling pathway. MethodsA total of 30 male rats were randomized into sham-operated group (sham group), spinal cord ischemia/reperfusion injury group (I/R group) and I/R + xenon post-conditioning group (Xe group), with ten rats in each group. In the latter two groups, SCIRI was induced by clamping the abdominal aorta for 85 minutes followed by reperfusion for four hours. Xe group inhaled xenon and oxygen (1∶1) for one hour at one hour after initiation of reperfusion, while the other groups inhaled nitrogen and oxygen (1∶1) for one hour. After the reperfusion, they were assessed with Basso-Beattie-Bresnahan (BBB) scale and slanting board test. And then, their spinal cords of L3-5 were obtained. Nissl staining was used to count the number of normal neurons. Western blotting was used to detect the protein expression of Akt, p-Akt, p62, Beclin 1, microtubule-associated protein 1 light chain 3 (LC3) Ⅰ, LC3 Ⅱ. The mRNA expression of Beclin 1, p62 and LC3 Ⅱ in the spinal cord was measured with reverse transcription real-time quantitative polymerase chain reaction. ResultsCompared with the sham group, the BBB score and the maximum inclination of the slanting board test decreased, the count of normal neurons decreased, the protein expression of p62 and the p-Akt/Akt ratio decreased (P < 0.01), the protein and mRNA expression of Beclin 1 and LC3 Ⅱ, and the LC3 Ⅱ/LC3 Ⅰ ratio increased, the p62 mRNA expression decreased (P < 0.01) in the I/R group. Compared with the I/R group, the BBB score and the maximum inclination of the slanting board test increased, the count of normal neurons increased, the protein expression of p-Akt and p62 increased, the p-Akt/Akt ratio increased, the protein and mRNA expression of Beclin 1, LC3 Ⅱ and LC3 Ⅱ/LC3 Ⅰ ratio decreased, and the mRNA expression of p62 increased (P < 0.01) in Xe group. ConclusionXenon post-conditioning may relieve SCIRI in rats, which is related to activating Akt signaling pathway to inhibit autophagy.
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Objective To explore the influence of family history of diabetes and central obesity on prediabetes(Pre-DM)and their interaction.Methods Based on the REACTION studyduring August December 2011 in Dalian,2587 individuals aged≥40 with normal blood glucose(BG)were divided into newly diagnosed Pre-DM(n=522)and BG normal group(NC,n=2065)during follow-up.The influence of family history of DM and central obesity on prediabetes and their interaction were analyzed.Results The age,SBP,DBP,BMI,WC,HDL-C,LDL-C,TG,ALT,GGT,FPG,2 hPG,HbA1c,FIns,HOMA-IR,SUA and the incidence of hypertension,fatty liver disease,dyslipidemia,overweight/obesity and central obesity in Pre-DM group were all higher than those in NC group(P<0.05).Multivariate logistic regression analysis showed that family history of diabetes and central obesity were risk factors for Pre-DM.After adjustment,no significant multiplicative interaction was shown between diabetes family history and central obesity on the risk of Pre-DM(P=0.764).Quantitative analysis of interaction showed that RERI=0.110,S=1.112 and AP=0.053,suggesting that DM family history and central obesity have no significant additive interaction on the risk of Pre-DM.Conclusion The family history of DM and central obesity are both associated with the occurrence of Pre-DM,but there is no significant interaction.
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italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC50 values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.
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Rice stripe virus (RSV) transmitted by the small brown planthopper causes severe rice yield losses in Asian countries. Although viral nuclear entry promotes viral replication in host cells, whether this phenomenon occurs in vector cells remains unknown. Therefore, in this study, we systematically evaluated the presence and roles of RSV in the nuclei of vector insect cells. We observed that the nucleocapsid protein (NP) and viral genomic RNAs were partially transported into vector cell nuclei by utilizing the importin α nuclear transport system. When blocking NP nuclear localization, cytoplasmic RSV accumulation significantly increased. In the vector cell nuclei, NP bound the transcription factor YY1 and affected its positive regulation to FAIM. Subsequently, decreased FAIM expression triggered an antiviral caspase-dependent apoptotic reaction. Our results reveal that viral nuclear entry induces completely different immune effects in vector and host cells, providing new insights into the balance between viral load and the immunity pressure in vector insects.
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Animais , Núcleo Celular , Hemípteros/metabolismo , Insetos Vetores/genética , Insetos , Proteínas do Nucleocapsídeo/metabolismo , Oryza , Doenças das Plantas , Tenuivirus/metabolismo , Replicação ViralRESUMO
Acute leukemia (AL) is a kind of malignant clonal disease of hematopoietic stem cells. Rearrangement of mixed lineage leukemia (MLL) gene can be observed in about 5%-10% of AL patients. Currently, AL patients with MLL-rearrangements (MLL-r) lack effective treatment and are usually associated with poor prognoses. Recent studies have shown that many epigenetic regulators are directly or indirectly involved in the occurrence and development of AL carrying MLL-r (MLL), which provides a biological basis for the use of epigenetic regulation strategies to treat MLL. In this review, we start from the epigenetic regulation mechanism of MLL, and select representative drug targets to briefly analyze the relationship between each target and MLL and summarize the development progress of their inhibitors, hoping to provide reference for the subsequent research and development of drugs for the treatment of MLL.
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Background At present, the evaluation of water quality in public swimming places mostly adopts the single index evaluation method, ignoring the possible correlation between the indicators, the problem of information overlap between the indicators, and the differences between the swimming places with single or multiple unqualified water quality indicators. Objective To evaluate water quality in public swimming places in Chongqing objectively, intuitively, and comprehensively. Methods In 2020, a stratified random sampling method was used to investigate seven water quality indicators of 112 public swimming places in the central urban area, the new downtown urban area, the northeastern area, and the southeastern area of Chongqing. The selected indicators were free residual chlorine, turbidity, pH, free residual chlorine in disinfection pool of feet, urea, total plate count, and coliform bacteria. Principal component analysis was utilized to comprehensively evaluate water quality of swimming places by calculating principal component characteristic values and comprehensive evaluation values. Results The qualification rates of free residual chlorine, turbidity, pH, free residual chlorine in disinfection pool of feet, urea, total plate count, and coliform bacteria were 91.30%, 89.40%, 91.30%, 91.30%, 99.00%, 95.20%, and 86.50%, respectively, and the P50 values were 0.455 mg·L−1, 0.59 NTU, 7.352, 6.63 mg·L−1, 0.78 mg·L−1, 8 CFU·mL−1, and 0 CFU·100mL−1, respectively. The results of principal component analysis showed that KMO=0.573, P<0.001; four principal components were extracted, the eigenvalues of each principal component were 2.990, 1.624, 0.854, and 0.617, respectively, and the cumulative contribution rate was 86.928%. The comprehensive values of Banan District, Beibei District, Bishan District, Fengdu County, Fengjie County, Jiangbei District, Nan'an District, Nanchuan District, Pengshui County, Qianjiang District, Rongchang District, Shizhu County, Tongnan District, Wanzhou District, Yongchuan District, Yuzhong District, Changshou District, and Zhongxian County were −0.139, 0.228, 0.587, 0.042, −3.365, 0.587, 0.597, 0.587, 0.587, 0.189, −1.127, −0.201, −0.181, 0.587, 0.416, 0.587, 0.587, −0.098, and 0.043, respectively. The comprehensive evaluation values (P50) of the central urban area, the new downtown urban area, the southeastern area, and the northeastern area of Chongqing were 0.587, 0.587, −0.181, and 0.043, respectively. Conclusion The hygienic status of water in public swimming places in Chongqing is above average in China, but there are still potential health problems in turbidity and bacterial pollution in the southeastern area and Fengjie County of Chongqing.
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The α-conotoxins are peptide toxins that are identified from the venom of marine cone snails and they hold outstanding potency on various subtypes of nicotinic acetylcholine receptors (nAChRs). nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, so nAChR dysfunctions have been involved in a variety of severe pathologies. Four types of α-3/5 conotoxins MI, MIA, MIB and MIC have been found from Conus magus. Among them, the activity and selectivity of MIA and MIB have not been well studied. In this study, four α-3/5 conotoxins MI, MIA, MIB and MIC were synthesized by solid peptide synthesis method, and the bioactivities of them were screened by double electrode voltage clamp electrophysiology. The results showed that MIA and MIB selectively inhibited muscle type acetylcholine receptors with IC50 values of 14.45 and 72.78 nmol·L-1, respectively, which are slightly weaker than MI and MIC. Molecular docking results have shown MIA and MIB interact with muscle-type nAChRs with similar mechanism. The reasons for activity differences may relate to the size of the N-terminal amino acids. Together, the conotoxins MIA and MIB may have the potential to develop as a tool for detect the function of muscle type nAChRs, as well as the diagnosis or treat of related diseases.
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Objective:To analyze and discuss the application value and teaching effect of simulate patients (SP)-assisted problem-based learning (PBL) combined with team-based learning (TBL) mode in pediatric first aid teaching, in order to provide a new reference for the reform of standardized residency training and teaching mode of pediatrics in the new era in China.Methods:A total of 103 residents who participated in the standardized training in the Department of Pediatrics of Hunan Children's Hospital from January 2018 to December 2020 were selected as the research objects, and they were divided into the control group (50 cases) and the experimental group (53 cases). The control group adopted the previous teaching mode of residents, while the experimental group adopted the SP-assisted PBL combined with TBL mode. In this study, SPSS 22.0 software was used for t test and chi-square test. Results:The examination scores of the experimental group in the theoretical knowledge of pediatric first aid, clinical thinking and skills, and application of pediatric first aid skills were higher than those in the control group [(86.98±3.42), (85.69±5.13), (89.62±4.75)] vs. [(77.23±4.16), (81.16±3.96), (76.54±5.78)], with statistically significant differences between the two groups ( P<0.05). The questionnaire survey showed that the clinical thinking and pediatric emergency skills, doctor-patient communication ability, teamwork ability and other aspects of the experimental group were significantly better than those of the control group ( P<0.05). Conclusion:The SP-assisted PBL combined with TBL mode can produce positive effects in the standardized residency training of pediatrics, which will help residents better master pediatric first aid skills, improve their clinical comprehensive capabilities, and be more conducive to improving the quality of pediatric residency training, which is worth promoting in the new era.
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Objective:To observe the changes of skeletal muscle indexes in elderly patients with type 2 diabetes complicated with sarcopenia treated with sitagliptin and acarbose.Methods:A total of 60 patients over 60 years old with type 2 diabetes complicated with sarcopenia in Dalian Municipal Central Hospital from January 2019 to January 2020 were selected and divided into two groups by random number table method.One group received sitagliptin and metformin,and the other group received acarbose and metformin. The changes of skeletal muscle indexes, glucagon-like peptides-1 (GLP-1), insulin resistance index (HOMA-IR) and inflammatory indexes were compared between the two groups at baseline and 36 weeks after treatment.Results:After treatment, the skeletal muscle index (SMI) of sitagliptin group was increased (5.94 ± 1.52 vs. 5.99 ± 1.52), and the difference was statistically significant ( P<0.05). Muscle strength and SMI decreased in acarbosse group (18.75 ± 4.64 vs. 17.72 ± 4.44, 6.09 ± 1.74 vs. 6.00 ± 1.71), with statistical significance ( P<0.05). GLP-1 increased in sitagliptin group, 0 min: (10.65 ± 1.68) pmol/L vs. (12.41 ± 1.88) pmol/L; 60 min: (22.79 ± 2.85) pmol/L vs. (25.51 ± 2.79) pmol/L; 120 min: (24.26 ± 2.94) pmol/L vs. (29.49 ± 2.91) pmol/L; 180 min: (11.68 ± 1.84) pmol/L vs. (12.88 ± 1.83) pmol/L. There were significant differences ( P<0.05). HOMA-IR and CRP decreased: 4.73 ± 3.04 vs. 3.16 ± 2.41, (2.39 ± 0.50) mg/L vs. (2.33 ± 0.43) mg/L, and the differences were statistically significant ( P<0.05). HOMA-IR in acarbose group decreased after treatment (5.80 ± 3.94 vs. 4.00 ± 1.63), and the difference was statistically significant ( P<0.05). Comparison between the two groups after treatment, the decreased value of muscle strength in sitagliptin group was less than that in acarbose group, and the difference was statistically significant ( P<0.05). GLP-1 and overall GLP-1 area under the curve in sitagliptin group were higher than those in acarbose group (67.64 ± 6.81 vs. 58.98 ± 6.72), with statistical significance ( P<0.05). HOMA-IR and CRP in sitagliptin group were lower than those in acarborose group: 3.16 ± 2.42 vs. 4.00 ± 1.63, (2.33 ± 0.43) mg/L vs. (2.41 ± 0.70) mg/L, with statistical significances ( P<0.05). Conclusions:Sitagliptin therapy improves muscle mass and protects muscle strength in elderly patients with type 2 diabetes mellitus and sarcopenia.
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Objective:To observe the therapeutic effect of echinacoside (ECH) on liver injury and glucose metabolism disorder in sepsis rats induced by cecal ligation and puncture (CLP), and to explore its possible mechanism.Methods:Forty eight male Sprague Dawley (SD) rats were randomly divided into four groups: sham group (sham), model group (CLP), treatment group (CLP+ ECH) and inhibitor group (CLP+ ECH+ EX527). The sham group only received laparotomy, and the model group underwent CLP. The treatment group was intragastric administration of echinacea (30 mg/kg) every day after CLP modeling. The inhibitor group was injected with silence information regulator 1 (SIRT1) inhibitor EX527 (5 mg/kg) one hour before CLP, and then treated the same as the treatment group. Fasting blood glucose, insulin and serum biochemical indexes were detected in virous groups. The serum levels of interleukin (IL)-1 β, IL-6 and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). 2′, 7′- dichlorofluorescein diacetate (DCFH-DA) staining was used to observe the production of reactive oxygen species (ROS) in liver tissue of rats in each group; hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue in each group; The expressions of SIRT1, glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and phosphorylated protein ki-nase B(p-AKT) were detected by Western blot.Results:Compared with sham group, the levels of serum glucose, serum insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), ROS, IL-1β, IL-6 and TNF-α in model group increased, while the liver glycogen and survival rate decreased (all P<0.05). After echinacoside treatment, the serum glucose, serum insulin, ALT, AST, ROS , IL-1β, IL-6 and TNF-α levels decreased, and the liver glycogen and survival rate increased (all P<0.05); After SIRT1 inhibitor intervention, the levels of serum insulin, ALT, AST, IL-6 and ROS in the inhibitor group increased ( P<0.05). HE staining showed that there were infiltration and necrosis of inflammatory cells in the liver tissue of model group, and echinacoside could significantly reduce the focal and massive necrosis; Western blot showed that compared with the sham group, the expression levels of SIRT1, p-STAT3 and p-AKT protein in the model group decreased, while the expression levels of G6Pase and PEPCK protein increased ( P<0.05); After echinacoside treatment, the expression levels of SIRT1, p-STAT3 and p-AKT increased, while the expression levels of G6Pase and PEPCK decreased ( P<0.05). After SIRT1 inhibitor intervention, the expression of SIRT1, p-STAT3 and p-AKT protein decreased, and the expression of G6Pase and PEPCK protein increased in the inhibitor group ( P<0.05). Conclusions:Echinacoside is a potential therapeutic agent for sepsis associated liver injury and glucose metabolism disorders, which may play a role by targeting SIRT1 to activate STAT3 and AKT in the liver.
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With the application of high throughput sequencing and other technologies, in recent years people have found that bacteria are not only the causative factors of common breast diseases such as mastitis, but also may be involved in the occurrence and development of breast cancer. There are unique bacterial communities in the internal tissues of the breast, and their existence may be related to the incidence of breast cancer. Recent studies have found that intestinal flora may also affect the incidence of breast cancer by regulating estrogen and other pathways. Further exploration of the influence of bacteria on breast cancer will provide new ideas for diagnosis and treatment of breast cancer.
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GeXIVA[1,2] is a new type of conotoxin recently discovered in the transcriptome of Conus generalis and it is expected to be used clinically as a new type of analgesic. This study established and verified a sandwich enzyme-linked immunosorbent assay method for the marine drug GeXIVA[1,2] in the plasma of rats and Beagle dogs. The mouse monoclonal antibody 4B2 and biotin-labeled rabbit polyclonal antibody 2# were developed. The checkerboard method was used to optimize the antibody pairing concentration, minimum dilution ratio, incubation temperature, and incubation time to establish an antibody sandwich ELISA detection method. Verify the established testing methods. The established ELISA method has a quantitative range of 1.25-80 ng·mL-1 in rat and Beagle plasma. The precision, accuracy, selectivity, specificity, stability, dilution linearity, and hook effect all meet the requirements for biological sample analysis. All the procedures for the animal experiments were approved by the Animal Ethics Committee of the Institute (Permit Number: IACUC-DWZX-2020-698). This method can support the preclinical pharmacokinetic study of the marine drug GeXIVA.
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The cyanuric chloride linkers have been used for cyclizing polypeptide, but not used for α-conotoxin, the peptides with rich disulfide bonds and more amino acid residues. In this study, cyclic peptides c[A10L]PnIA-1-4 were synthesized efficiently by lysine assisted cyanuric chloride linkers with 28.92%-52.00% yields. The activity evaluation showed that the IC50 values of c[A10L]PnIA-1 against α7 and α3β2 nAChR subtypes were 5 and 7 times higher than [A10L]PnIA respectively, and the subtype selectivity was maintained. The results of circular dichroism show that this cyclization method had no significant effect on its secondary structure. Compared with the commonly used head-to-tail cyclization in conotoxin cyclization, this method has the advantages of rapid reaction and high yield, which is expected to be further applied to the cyclization study of various α-conotoxins.
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italic>α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems, and is closely related to a variety of neurological diseases and inflammation response. α-Conotoxin [A10L]PnIA, as an antagonist targeting α7 nAChR, plays an important role in studying the physiological and pathological processes involved in α7 nAChR. [A10L]PnIA was labeled with fluorescein 5-carboxytetramethylrhodamine, and the active peptide ([A10L]PnIA-F) was obtained by a two-step oxidative folding procedure in vitro. The Xenopus oocyte expression system and the two-electrode voltage clamp technique were used to identify the potency of [A10L]PnIA-F fluorescent peptide, and its cytotoxicity was detected by mouse macrophages and CCK8 method. The molecular weight of [A10L]PnIA-F fluorescent peptide was identified by mass spectrometry as 2 077.28 Da, which was consistent with the theoretical value. Electrophysiological determination of its half-maximal inhibitory concentration (IC50) for α7 nAChR is 17.32 nmol·L-1, which is consistent with [A10L]PnIA (IC50, 13.84 nmol·L-1). The cytotoxicity test results showed that within the concentration range of 5 nmol·L-1 to 10 μmol·L-1, there was no significant inhibition on the growth of mouse macrophages. The results showed that the α-conotoxin fluorescent probe [A10L]PnIA could provide pharmacological tools for the research of α7 nAChR-related neurophysiological and pathological mechanisms.
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Dendrobium huoshanense is a precious medicinal plant belonging to Dendrobium of Orchidaceae. It is a special medicinal material and extremely scarce in Huoshan county, Anhui province. At present, D. huoshanense has been greatly protected, which also makes it possible to industrialize relying on tissue culture and artificial cultivation technology. Three main planting methods were utilized for cultivating D. huoshanense including facility cultivation, under forest cultivation and simulative habitat cultivation. Firstly, the three cultivation modes and technical characteristics of D. huoshanense were compared and analyzed, and it was found that the ecological environment of D. huoshanense cultivated in the simulated environment was closer to that of wild D. huoshanense. Secondly, based on comparing the characters and quality of three cultivation modes, the results showed that the shape of D. huoshanense cultivated in simulated environment was more similar to that of "grasshopper thigh" recorded in Bencao Jing Jizhu, and its quality was better than that of facilities and under forest cultivation. The comprehensive benefit comparison of three modes showed that the simulated cultivation had high income, the lowest input-output ratio and significant economic benefit. The quality of cultivated D. huoshanense was further evaluated from four aspects of "excellent environment" "excellent shape" "high quality" "excellent effect", which summarized the comprehensive advantages of simulative habitat cultivation of D. huoshanense as follows: the original habitat and site environment of simulated wild D. huoshanense, the closer shape to the wild, the more content of main medicinal components, and higher economic benefit and better efficacy. The quality of D. huoshanense was improved by the use of simulative habitat cultivation, which has practical significance to guide its large-scale cultivation.
Assuntos
Dendrobium , Ecossistema , Florestas , Plantas MedicinaisRESUMO
OBJECTIVE@#To investigate the clinical and immunological features of cardiac involvement in patients with anti-synthetase syndrome (ASS).@*METHODS@#In the study, 96 patients diagnosed with ASS hospitalized in the Department of Rheumatology and Immunology, Peking University People's Hospital from April 2003 to November 2020 were included. The patients were divided into two groups according to whether they were accompanied with cardiac involvement. Demographic features, clinical characteristics (Gottron's sign/papules, muscle damage, etc.), comorbidities, laboratory indices (creatine kinase, inflammatory indicators, immunoglobulin, complement, lymphocyte subset, autoantibodies, etc.) were collected and the differences between the two groups were analyzed statistically.@*RESULTS@#The prevalence of cardiac involvement in the patients with ASS was 25.0% (24/96). The ASS patients complicated with cardiac involvement presented with elevated cardiac troponin I (cTnI, 75.0%, 18/24), pericardial effusion (33.3%, 8/24), reduction of left ventricular function (33.3%, 8/24) and valves regurgitation (33.3%, 8/24). The age of onset of the patients with cardiac involvement was older than that of the patients without cardiac involvement [(54.58±10.58) years vs. (48.47±13.22) years, P=0.043). Arthritis was observed less frequently in the patients with cardiac involvement than those without cardiac involvement (37.5% vs. 61.1%, P=0.044). In addition, rapidly progressive interstitial lung disease (54.2% vs. 30.6%, P=0.037) was observed more frequently in the patients with cardiac involvement than those without cardiac involvement. As compared with the ASS patients without cardiac involvement, C-reactive protein (CRP) [(13.55 (8.96, 38.35) mg/L vs. 4.60 (1.37, 17.40) mg/L, P=0.001], and lactate dehydrogenase (LDH) [408.0 (255.0, 587.0) U/L vs. 259.5 (189.8, 393.8) U/L, P=0.007] were significantly higher in the patients with cardiac involvement. Anti-Ro-52 antibody was detected more commonly in the ASS patients with cardiac involvement compared with the patients without cardiac involvement (91.7% vs. 69.4%, P=0.029). No significant differences were found in the comorbidities, alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), erythrocyte sedimentation rate (ESR), ferritin (Fer), immunoglobulin G (IgG), complement 3 (C3), complement 4 (C4), lymphocyte subset between the two groups.@*CONCLUSION@#Cardiac involvement is common in ASS, mainly manifested as myocardial damage. It is necessary to be aware of cardiac complications in patients with elevated CRP, elevated LDH and positive anti-Ro-52 antibody.