Objective: To explore the antibacterial activity of combined use of Shuanghuanglian and cefoperazone sulbactam sodium on resistant strains of Pseudomonas aeruginosa. Methods: The Pseudomonas aeruginosa strains which w...Objective: To explore the antibacterial activity of combined use of Shuanghuanglian and cefoperazone sulbactam sodium on resistant strains of Pseudomonas aeruginosa. Methods: The Pseudomonas aeruginosa strains which were sensitive and resistant to cefoperazone sulbactam sodium were selected to prepare different test bacterial solutions respectively;The experimental liquid of Shuanghuanglian and Cefoperazone Sulbactam Sodium were prepared separately and set as different test groups and control groups;The Drug Sensitivity Tests of Shuanghuanglian and cefoperazone sulbactam sodium at different concentration gradients which were used alone or used in combination were carried out for different strains with sensitivity and resistance, And use standard entry as a reference control. Result: The results of drug sensitivity test of Shuanghuanglian combined with Cefoperazone-Sulbactam sodium against the resistant strains of Pseudomonas aeruginosa were compared with the results of drug sensitivity test of the two separately used, and the difference was statistically significant (P 〈 0.05) [The drug sensitivity test results of Shuanghuanglian and cefoperazone sulbactam sodium to Pseudomonas aeruginosa resistant strains were statistically significant compared with the drug sensitivity test results of Shuanghuanglian and Cefoperazone Sulbactam Sodium used separately (P 〈 0.05)];There was a dependence between strains and concentration in the effect of the combination of the two drugs. Conclusion: The combination of Shuanghuanglian and cefoperazone sulbactam sodium has synergistic antibacterial or bactericidal effect on Pseudomonas aeruginosa resistant strains. .展开更多
To develop near-infrared （NIR） reflectance spectroscopic methods for the quantitative analysis of cefoperazone sodium/ sulbactam sodium from different manufacturers for injection powder medicaments. Various powders ...To develop near-infrared （NIR） reflectance spectroscopic methods for the quantitative analysis of cefoperazone sodium/ sulbactam sodium from different manufacturers for injection powder medicaments. Various powders of cefoperazone sodium/ sulbactam sodium were directly analyzed by non-destructive NIR reflectance spectroscopy using the spectrometer EQUINOX55. Two quantitative methods via integrating sphere （IS） and fiberoptic probe （FOP） models were explored from 6 batches of commercial samples and 42 batches of laboratory samples at a content ranging from 30% to 70% for cefoperazone and 60% to 20% for sulbactam. The root mean square errors of cross validation （RMSECV） and the root mean square errors of prediction （RMSEP） of IS were 1.79% and 2.85%, respectively, for cefoperazone sodium, and were 1.86% and 3.08%, respectively, for sulbactam sodium; and those of FOP were 2.93% and 2.92%, respectively, for cefoperazone sodium, and were 2.23% and 3.01%, respectively, for sulbactam sodium. Based on the ICH guidelines and Ref. 12, the quantitative models were then evaluated in terms of specificity, linearity, accuracy, precision, robustness and model transferability. The non-destructive quantitative NIR methods used in this study are applicable for rapid analysis of injectable powdered drugs from different manufacturers.展开更多
BACKGROUND Respiratory tract infections in the elderly are difficult to cure and can easily recur,thereby posing a great threat to patient prognosis and quality of life.AIM To investigate the therapeutic effects of di...BACKGROUND Respiratory tract infections in the elderly are difficult to cure and can easily recur,thereby posing a great threat to patient prognosis and quality of life.AIM To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection.METHODS Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study(n=37;treated with cefoperazone sodium/sulbactam sodium)or control(n=37;treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support)group.Both groups were treated for 7 d.Time to symptom relief(leukocyte recovery;body temperature recovery;cough and sputum disappearance;and rale disappearance time),treatment effect,and laboratory indexes[procalcitonin(PCT),C-reactive protein(CRP),white blood cell count(WBC),and neutrophil percentage(NE)]before and 7 d after treatment and the incidence of adverse reactions were assessed.RESULTS In the study group,the time to WBC normalization(6.79±2.09 d),time to body temperature normalization(4.15±1.08 d),time to disappearance of cough and sputum(6.19±1.56 d),and time to disappearance of rales(6.68±1.43 d)were shorter than those of the control group(8.89±2.32 d,5.81±1.33 d,8.77±2.11 d,and 8.69±2.12 d,respectively;P=0.000).Total effective rate was higher in the study group(94.59%vs 75.68%,P=0.022).Serum PCT(12.89±3.96μg/L),CRP(19.62±6.44 mg/L),WBC(20.61±6.38×10^(9)/L),and NE(86.14±7.21%)levels of the study group before treatment were similar to those of the control group(14.05±4.11μg/L,18.79±5.96 mg/L,21.21±5.59×10^(9)/L,and 84.39±6.95%,respectively)with no significant differences(P=0.220,0.567,0.668,and 0.291,respectively).After 7 d of treatment,serum PCT,CRP,WBC,and NE levels in the two groups were lower than those before treatment.Serum PCT(2.01±0.56μg/L),CRP(3.11±1.02 mg/L),WBC(5.10±1.83×10^(9)/L),and NE(56.35±7.17%)levels were lower in the study group than in the control group(3.29±0.64μg/L,5.67±1.23 mg/L,8.13±3.01×10^(9)/L,and 64.22±8.08%,respectively;P=0.000).There was no significant difference in the incidence of adverse reactions between the groups(7.50%vs 12.50%,P=0.708).CONCLUSION Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.展开更多
Objective: To investigate the antibacterial effect of baicalin combined with cefoperazone-sulbactam sodium on drug-resistant strains of Pseudomonas aeruginosa. Method: Pseudomonas aeruginosa strains that are sensitive...Objective: To investigate the antibacterial effect of baicalin combined with cefoperazone-sulbactam sodium on drug-resistant strains of Pseudomonas aeruginosa. Method: Pseudomonas aeruginosa strains that are sensitive and resistant to cefoperazone-sulbactam sodium were selected to prepare different test bacterial solutions respectively;The test solutions of baicalin and cefoperazone sulbactam sodium were prepared respectively, and different test groups and control groups were set up;The drug sensitivity tests of different concentration gradients of baicalin and cefoperazone sulbactam sodium used alone and in combination were carried out for different sensitive and drug-resistant strains, and the standard strains were used as parallel control. Result: The drug susceptibility test results of the combined use of baicalin and cefoperazone-sulbactam against Pseudomonas aeruginosa drug-resistant strains were compared with the drug susceptibility results of the two used separately, and the difference was statistically significant (P Pseudomonas aeruginosa.展开更多
Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in viv...Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.展开更多
BACKGROUND The sodium/glucose cotransporter-2 inhibitors(SGLT-2i)and glucagon-like-1 receptor agonists(GLP-1RA)are antidiabetic agents effective both in hemoglobin A1c(HbA1c)reduction(with a low risk of hypoglycemia)a...BACKGROUND The sodium/glucose cotransporter-2 inhibitors(SGLT-2i)and glucagon-like-1 receptor agonists(GLP-1RA)are antidiabetic agents effective both in hemoglobin A1c(HbA1c)reduction(with a low risk of hypoglycemia)and cardiovascular event prevention.In patients with type 2 diabetes,the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.AIM To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.METHODS We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with(1)GLP-1RA on top of SGLT-2i,(2)SGLT-2i on top of GLP-1RA compared to(3)simultaneous addition of both agents.The primary study endpoint was the proportion of participants with HbA1c<7.0%and/or 5%bodyweight reduction.Secondary outcomes included changes in fasting plasma glucose(FPG),prandial plasma glucose,lowdensity lipoprotein cholesterol,estimated glomerular filtration rate(eGFR),and cardiovascular(CV)incidents assessment over a follow-up period of 12 mo.RESULTS The majority of patients were over 65-years-old,had diabetes duration for more than 10 years.The initial body mass index was 39.41±5.49 kg/m2 and HbA1c 8.32±1.26%.Around half of the patients in all three groups achieved target HbA1c below 7%.A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy.The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group(P=0.021),and 5%weight loss was dominantly achieved in the simultaneous therapy group(P=0.044).A composite outcome(reduction of HbA1c below 7%(53 mmol/mol)with 5%weight loss)was achieved in 32.3%of total patients included in the study.Only 18.2%of patients attained composite outcome defined as HbA1c below 7%(53 mmol/mol)with 5%weight loss and low-density lipoprotein cholesterol<2.5 mmol/L.There were no significant differences between treatment groups.No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.CONCLUSION Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control,although it remains to be determined whether simultaneous or sequential intensification is better.展开更多
WS_(2)with layered graphite-like structure as anode for sodium ion batteries has high specific capacity.However,the poor cycling performance and rate capability of WS_(2)caused by the low electronic conductivity and s...WS_(2)with layered graphite-like structure as anode for sodium ion batteries has high specific capacity.However,the poor cycling performance and rate capability of WS_(2)caused by the low electronic conductivity and structure changes during cycles inhibit its practical application.Herein,metallic phase(1T)W_(x)Mo_(1−x)S2(x=1,0.9,0.8 and 0.6)with high electronic conductivity and expanded interlayer spacing of 0.95 nm was directly prepared via a simple hydrothermal method.Specially,1T W_(0.9)Mo_(0.1)S_(2)as anode for sodium ion batteries displays high capacities of 411 mAh g^(-1)at 0.1 A g^(-1)after 180 cycles and 262 mAh g^(-1)at 1 A g^(-1)after 280 cycles and excellent rate capability(245 mAh g^(-1)at 5 A g^(-1)).The full cell based on Na_(3)V_(2)(PO_(4))_(2)O_(2)F/C cathode and 1T W_(0.9)Mo_(0.1)S_(2)anode also exhibits high capacity and good cycling performance.The irreversible electrochemical reaction of 1T W_(0.9)Mo_(0.1)S_(2)with Na ions during first few cycles results in the main products of W-Mo alloy and S.The strong adsorption of W-Mo alloy with polysulfides can effectively suppress the dissolution and shuttle effect of polysulfides,which ensures the excellent cycling performance of 1T W_(0.9)Mo_(0.1)S_(2).展开更多
Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chlorid...Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.展开更多
Sodium 3,5-bis(hydroxyimino)-1-methyl-2,4,6-trioxocyclohexanide C7H5N2NaO5 (I) has been isolated as the only product of the reaction of nitrosation of methylphloroglucinol. The structure of the titled compound has bee...Sodium 3,5-bis(hydroxyimino)-1-methyl-2,4,6-trioxocyclohexanide C7H5N2NaO5 (I) has been isolated as the only product of the reaction of nitrosation of methylphloroglucinol. The structure of the titled compound has been determined from single crystal X-ray diffraction data. The hydrated C7H5N2NaO52.5H2O crystallizes in the monoclinic space group C2/c, with a(?) 16.408(3);b(?) 12.446(3);c(?) 13.716(3);(o) 126.34(3). The planar organic anion exists in a triketo-dihydroxyimino form with the C–O and C–N distances from 1.220(2) to 1.271(2)?? and from 1.292(2) to 1.293?? respectively. In the IR spectrum of I, the sharp absorption band occurred at 1681 cm-1 due to C=O stretching indicating the strong H-interactions. The correlations of theoretical (DFT-B3LYP/aug-cc-pVDZ) and experimental UV-vis absorption spectra in neutral and alkaline ethanolic solutions showed the existence of hydroxyimino-nitroso tautomerism while ionization of I.展开更多
目的:探究阿魏酸钠(SF)通过miR-216b-3p/Nrf2通路对缺氧缺血性脑病(HIE)胚胎大鼠大脑的干预作用以及减轻氧化应激损伤的作用机制。方法:将成年雌性SD大鼠和雄鼠,按照3∶1比例合笼获得怀孕的雌鼠。然后将孕鼠分为假手术组(sham)、缺氧缺...目的:探究阿魏酸钠(SF)通过miR-216b-3p/Nrf2通路对缺氧缺血性脑病(HIE)胚胎大鼠大脑的干预作用以及减轻氧化应激损伤的作用机制。方法:将成年雌性SD大鼠和雄鼠,按照3∶1比例合笼获得怀孕的雌鼠。然后将孕鼠分为假手术组(sham)、缺氧缺血性脑病模型组(HIE)、SF低剂量组(HIE+SF-L)和SF高剂量组(HIE+SF-H)。通过无创止血钳夹闭子宫两侧动脉和卵巢血管法制备胚胎大鼠HIE模型。SF治疗组腹膜腔注射SF。采用HE染色观察胚胎大鼠大脑皮质的病理变化;免疫荧光观察核因子红细胞系2相关因子2(Nrf2)、过氧化还原酶1(PRDX1)的表达情况;Western Blot检测胚胎大鼠脑组织中Nrf2和PRDX1蛋白的表达;real time RT-PCR检测miR-216b-3p的表达以及Nrf2和PRDX1的mRNA表达;WST-8法和TBA法检测脑组织中的超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:与sham组对比,HIE组胚胎大鼠的大脑损伤加重,病理改变明显;HIE组中Nrf2蛋白表达和mRNA水平降低(P<0.05),PRDX1的蛋白水平和mRNA水平显著上调(P<0.05),miR-216b-3p表达水平显著升高(P<0.05);并且Nrf2的平均荧光强度显著降低(P<0.05),PRDX1的平均荧光强度显著增加(P<0.05);SOD活性显著下调,MDA含量显著增加(P<0.05)。与HIE组对比,各剂量SF组的大脑皮质病理结构明显改善,脑损伤减轻;Nrf2和PRDX1的蛋白表达、mRNA水平以及平均荧光强度均显著上升(P<0.05);miR-216b-3p表达水平均显著下调,以SF高剂量组下调最为显著(P<0.05);并且SOD活性显著上调,MDA含量显著下调(P<0.05)。结论:SF通过miR-216b-3p/Nrf2信号通路在HIE的发生发展过程中发挥重要作用,并减轻胚胎大鼠受到的氧化应激损伤。展开更多
文摘Objective: To explore the antibacterial activity of combined use of Shuanghuanglian and cefoperazone sulbactam sodium on resistant strains of Pseudomonas aeruginosa. Methods: The Pseudomonas aeruginosa strains which were sensitive and resistant to cefoperazone sulbactam sodium were selected to prepare different test bacterial solutions respectively;The experimental liquid of Shuanghuanglian and Cefoperazone Sulbactam Sodium were prepared separately and set as different test groups and control groups;The Drug Sensitivity Tests of Shuanghuanglian and cefoperazone sulbactam sodium at different concentration gradients which were used alone or used in combination were carried out for different strains with sensitivity and resistance, And use standard entry as a reference control. Result: The results of drug sensitivity test of Shuanghuanglian combined with Cefoperazone-Sulbactam sodium against the resistant strains of Pseudomonas aeruginosa were compared with the results of drug sensitivity test of the two separately used, and the difference was statistically significant (P 〈 0.05) [The drug sensitivity test results of Shuanghuanglian and cefoperazone sulbactam sodium to Pseudomonas aeruginosa resistant strains were statistically significant compared with the drug sensitivity test results of Shuanghuanglian and Cefoperazone Sulbactam Sodium used separately (P 〈 0.05)];There was a dependence between strains and concentration in the effect of the combination of the two drugs. Conclusion: The combination of Shuanghuanglian and cefoperazone sulbactam sodium has synergistic antibacterial or bactericidal effect on Pseudomonas aeruginosa resistant strains. .
基金National Key Technologies R&D Program Foundation of China (Grant No. 2006BAK04A11)
文摘To develop near-infrared （NIR） reflectance spectroscopic methods for the quantitative analysis of cefoperazone sodium/ sulbactam sodium from different manufacturers for injection powder medicaments. Various powders of cefoperazone sodium/ sulbactam sodium were directly analyzed by non-destructive NIR reflectance spectroscopy using the spectrometer EQUINOX55. Two quantitative methods via integrating sphere （IS） and fiberoptic probe （FOP） models were explored from 6 batches of commercial samples and 42 batches of laboratory samples at a content ranging from 30% to 70% for cefoperazone and 60% to 20% for sulbactam. The root mean square errors of cross validation （RMSECV） and the root mean square errors of prediction （RMSEP） of IS were 1.79% and 2.85%, respectively, for cefoperazone sodium, and were 1.86% and 3.08%, respectively, for sulbactam sodium; and those of FOP were 2.93% and 2.92%, respectively, for cefoperazone sodium, and were 2.23% and 3.01%, respectively, for sulbactam sodium. Based on the ICH guidelines and Ref. 12, the quantitative models were then evaluated in terms of specificity, linearity, accuracy, precision, robustness and model transferability. The non-destructive quantitative NIR methods used in this study are applicable for rapid analysis of injectable powdered drugs from different manufacturers.
文摘BACKGROUND Respiratory tract infections in the elderly are difficult to cure and can easily recur,thereby posing a great threat to patient prognosis and quality of life.AIM To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection.METHODS Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study(n=37;treated with cefoperazone sodium/sulbactam sodium)or control(n=37;treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support)group.Both groups were treated for 7 d.Time to symptom relief(leukocyte recovery;body temperature recovery;cough and sputum disappearance;and rale disappearance time),treatment effect,and laboratory indexes[procalcitonin(PCT),C-reactive protein(CRP),white blood cell count(WBC),and neutrophil percentage(NE)]before and 7 d after treatment and the incidence of adverse reactions were assessed.RESULTS In the study group,the time to WBC normalization(6.79±2.09 d),time to body temperature normalization(4.15±1.08 d),time to disappearance of cough and sputum(6.19±1.56 d),and time to disappearance of rales(6.68±1.43 d)were shorter than those of the control group(8.89±2.32 d,5.81±1.33 d,8.77±2.11 d,and 8.69±2.12 d,respectively;P=0.000).Total effective rate was higher in the study group(94.59%vs 75.68%,P=0.022).Serum PCT(12.89±3.96μg/L),CRP(19.62±6.44 mg/L),WBC(20.61±6.38×10^(9)/L),and NE(86.14±7.21%)levels of the study group before treatment were similar to those of the control group(14.05±4.11μg/L,18.79±5.96 mg/L,21.21±5.59×10^(9)/L,and 84.39±6.95%,respectively)with no significant differences(P=0.220,0.567,0.668,and 0.291,respectively).After 7 d of treatment,serum PCT,CRP,WBC,and NE levels in the two groups were lower than those before treatment.Serum PCT(2.01±0.56μg/L),CRP(3.11±1.02 mg/L),WBC(5.10±1.83×10^(9)/L),and NE(56.35±7.17%)levels were lower in the study group than in the control group(3.29±0.64μg/L,5.67±1.23 mg/L,8.13±3.01×10^(9)/L,and 64.22±8.08%,respectively;P=0.000).There was no significant difference in the incidence of adverse reactions between the groups(7.50%vs 12.50%,P=0.708).CONCLUSION Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.
文摘Objective: To investigate the antibacterial effect of baicalin combined with cefoperazone-sulbactam sodium on drug-resistant strains of Pseudomonas aeruginosa. Method: Pseudomonas aeruginosa strains that are sensitive and resistant to cefoperazone-sulbactam sodium were selected to prepare different test bacterial solutions respectively;The test solutions of baicalin and cefoperazone sulbactam sodium were prepared respectively, and different test groups and control groups were set up;The drug sensitivity tests of different concentration gradients of baicalin and cefoperazone sulbactam sodium used alone and in combination were carried out for different sensitive and drug-resistant strains, and the standard strains were used as parallel control. Result: The drug susceptibility test results of the combined use of baicalin and cefoperazone-sulbactam against Pseudomonas aeruginosa drug-resistant strains were compared with the drug susceptibility results of the two used separately, and the difference was statistically significant (P Pseudomonas aeruginosa.
基金supported by the Natural Science Foundation of Fujian Province,No.2020J02027the National Natural Science Foundation of China,No.31970461the Foundation of NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate,Fujian Maternity and Child Health Hospital,No.2022-NHP-05(all to WC).
文摘Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.
文摘BACKGROUND The sodium/glucose cotransporter-2 inhibitors(SGLT-2i)and glucagon-like-1 receptor agonists(GLP-1RA)are antidiabetic agents effective both in hemoglobin A1c(HbA1c)reduction(with a low risk of hypoglycemia)and cardiovascular event prevention.In patients with type 2 diabetes,the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.AIM To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.METHODS We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with(1)GLP-1RA on top of SGLT-2i,(2)SGLT-2i on top of GLP-1RA compared to(3)simultaneous addition of both agents.The primary study endpoint was the proportion of participants with HbA1c<7.0%and/or 5%bodyweight reduction.Secondary outcomes included changes in fasting plasma glucose(FPG),prandial plasma glucose,lowdensity lipoprotein cholesterol,estimated glomerular filtration rate(eGFR),and cardiovascular(CV)incidents assessment over a follow-up period of 12 mo.RESULTS The majority of patients were over 65-years-old,had diabetes duration for more than 10 years.The initial body mass index was 39.41±5.49 kg/m2 and HbA1c 8.32±1.26%.Around half of the patients in all three groups achieved target HbA1c below 7%.A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy.The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group(P=0.021),and 5%weight loss was dominantly achieved in the simultaneous therapy group(P=0.044).A composite outcome(reduction of HbA1c below 7%(53 mmol/mol)with 5%weight loss)was achieved in 32.3%of total patients included in the study.Only 18.2%of patients attained composite outcome defined as HbA1c below 7%(53 mmol/mol)with 5%weight loss and low-density lipoprotein cholesterol<2.5 mmol/L.There were no significant differences between treatment groups.No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.CONCLUSION Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control,although it remains to be determined whether simultaneous or sequential intensification is better.
基金the support from the National Science Foundation of China(22179071,51772169,51802261,52072217)the Major Technological Innovation Project of Hubei Science and Technology Department(2019AAA164)supported by the Research Project of Education Department of Hubei Province(D20191202)。
文摘WS_(2)with layered graphite-like structure as anode for sodium ion batteries has high specific capacity.However,the poor cycling performance and rate capability of WS_(2)caused by the low electronic conductivity and structure changes during cycles inhibit its practical application.Herein,metallic phase(1T)W_(x)Mo_(1−x)S2(x=1,0.9,0.8 and 0.6)with high electronic conductivity and expanded interlayer spacing of 0.95 nm was directly prepared via a simple hydrothermal method.Specially,1T W_(0.9)Mo_(0.1)S_(2)as anode for sodium ion batteries displays high capacities of 411 mAh g^(-1)at 0.1 A g^(-1)after 180 cycles and 262 mAh g^(-1)at 1 A g^(-1)after 280 cycles and excellent rate capability(245 mAh g^(-1)at 5 A g^(-1)).The full cell based on Na_(3)V_(2)(PO_(4))_(2)O_(2)F/C cathode and 1T W_(0.9)Mo_(0.1)S_(2)anode also exhibits high capacity and good cycling performance.The irreversible electrochemical reaction of 1T W_(0.9)Mo_(0.1)S_(2)with Na ions during first few cycles results in the main products of W-Mo alloy and S.The strong adsorption of W-Mo alloy with polysulfides can effectively suppress the dissolution and shuttle effect of polysulfides,which ensures the excellent cycling performance of 1T W_(0.9)Mo_(0.1)S_(2).
基金supported by a grant from Guangzhou Medical University,No.2008C24
文摘Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.
文摘Sodium 3,5-bis(hydroxyimino)-1-methyl-2,4,6-trioxocyclohexanide C7H5N2NaO5 (I) has been isolated as the only product of the reaction of nitrosation of methylphloroglucinol. The structure of the titled compound has been determined from single crystal X-ray diffraction data. The hydrated C7H5N2NaO52.5H2O crystallizes in the monoclinic space group C2/c, with a(?) 16.408(3);b(?) 12.446(3);c(?) 13.716(3);(o) 126.34(3). The planar organic anion exists in a triketo-dihydroxyimino form with the C–O and C–N distances from 1.220(2) to 1.271(2)?? and from 1.292(2) to 1.293?? respectively. In the IR spectrum of I, the sharp absorption band occurred at 1681 cm-1 due to C=O stretching indicating the strong H-interactions. The correlations of theoretical (DFT-B3LYP/aug-cc-pVDZ) and experimental UV-vis absorption spectra in neutral and alkaline ethanolic solutions showed the existence of hydroxyimino-nitroso tautomerism while ionization of I.
文摘目的:探究阿魏酸钠(SF)通过miR-216b-3p/Nrf2通路对缺氧缺血性脑病(HIE)胚胎大鼠大脑的干预作用以及减轻氧化应激损伤的作用机制。方法:将成年雌性SD大鼠和雄鼠,按照3∶1比例合笼获得怀孕的雌鼠。然后将孕鼠分为假手术组(sham)、缺氧缺血性脑病模型组(HIE)、SF低剂量组(HIE+SF-L)和SF高剂量组(HIE+SF-H)。通过无创止血钳夹闭子宫两侧动脉和卵巢血管法制备胚胎大鼠HIE模型。SF治疗组腹膜腔注射SF。采用HE染色观察胚胎大鼠大脑皮质的病理变化;免疫荧光观察核因子红细胞系2相关因子2(Nrf2)、过氧化还原酶1(PRDX1)的表达情况;Western Blot检测胚胎大鼠脑组织中Nrf2和PRDX1蛋白的表达;real time RT-PCR检测miR-216b-3p的表达以及Nrf2和PRDX1的mRNA表达;WST-8法和TBA法检测脑组织中的超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:与sham组对比,HIE组胚胎大鼠的大脑损伤加重,病理改变明显;HIE组中Nrf2蛋白表达和mRNA水平降低(P<0.05),PRDX1的蛋白水平和mRNA水平显著上调(P<0.05),miR-216b-3p表达水平显著升高(P<0.05);并且Nrf2的平均荧光强度显著降低(P<0.05),PRDX1的平均荧光强度显著增加(P<0.05);SOD活性显著下调,MDA含量显著增加(P<0.05)。与HIE组对比,各剂量SF组的大脑皮质病理结构明显改善,脑损伤减轻;Nrf2和PRDX1的蛋白表达、mRNA水平以及平均荧光强度均显著上升(P<0.05);miR-216b-3p表达水平均显著下调,以SF高剂量组下调最为显著(P<0.05);并且SOD活性显著上调,MDA含量显著下调(P<0.05)。结论:SF通过miR-216b-3p/Nrf2信号通路在HIE的发生发展过程中发挥重要作用,并减轻胚胎大鼠受到的氧化应激损伤。
