Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dysfunctions related to thinking, learning, and memory of the brain. AD has multiple pathological characteristics with complicated causes, constructing a suitable pathological model is crucial for the research of AD. Microfluidic chip technology integrates multiple functional units on a chip, which can realize microenvironmental control similar to the physiological environment. It is well applied in the construction of pathological model, early diagnosis as well as drug screening of AD. This paper focuses on the construction of AD microfluidic chips model from the perspective of cell type, culture formats and the chips structure as well as the research progress of microfluidic chips in AD application based on the pathological characteristics of AD, which will provide a reference for further elucidation of AD mechanism and drug development.

Objective:To investigate the changes of the distribution and drug resistance profile of bacteria from ICU children with lower respiratory tract infection (LRTI) in Suzhou City, Jiangsu Province from 2017 to 2022.Methods:From January 2017 to December 2022, a cross-sectional observational study on the bacterial spectrum analysis among intensive care unit (ICU) children with LRTI was conducted in Children′s Hospital of Soochow University. The bacteria was cultivated by culture methods from sputum samples, and identified by MALDI-TOF mass spectrometry. Drug sensitivity tests were performed by the VITEK2 Compact fully automated analysis system and the paper slide method. The χ2 test or Fisher′s exact probability was used to analyze the changes of the distribution of sputum culture-positive bacteria and drug resistance in ICU children. Results:The overall detection rate of sputum culture was 42.06% (1 182/2 810). Staphylococcus aureus (25.63%,303/1 182), Acinetobacter baumannii (13.62%,161/1 182) and Haemaphilus influenzae (13.28%,157/1 182) were the top three. Proportions of Acinetobacter baumannii (17.90% vs. 11.02%, χ2=11.17, P=0.001), especially carbapenem-resistant Acinetobacter baumannii (43.70% vs. 23.50%, χ2=15.21, P<0.001) increased significantly from 2020 to 2022. However, the proportions of Haemophilus influenzae (8.50% vs. 16.19%, χ2=14.27, P<0.001), Streptococcus pneumoniae (8.50% vs. 15.92%, χ2=13.42, P<0.001) and extended-spectrum-lactamase producing Escherichia coli (8.89% vs. 18.00%, χ2=5.45, P=0.025) decreased. Drug resistant results showed that Acinetobacter baumannii was obviously more resistant to imipenem ( χ2=4.43, P=0.035) and levofloxacin ( χ2=12.53, P<0.001), while more sensitive to minocycline ( χ2=8.34, P=0.004). Escherichia coli showed a significant increase in resistance to piperacillin tazobactam ( χ2=8.29, P=0.008) and cefoperazone sulbactam ( χ2=5.07, P=0.024) from 2020 to 2022; Klebsiella pneumoniae consistently maintained a resistance rate of more than 60% to first and second-generation cephalosporins, and remain susceptible to quinolones and carbapenems. Staphylococcus aureus remained highly susceptible to levofloxacin (drug resistance rate: 2.31%,7/303) and sulfamethoxazole/trimethoprim (drug resistance rate: 4.95%,15/303) from 2020 to 2022. Conclusion:Higher detection and resistance rates of Acinetobacter baumannii from sputum culture in ICU children from 2020 to 2022 were explored. Resistance of Escherichia coli to β-lactamase inhibitor combinations was more serious. Regular monitoring the changes of the etiology of respiratory tract infections in ICU Children is particularly important for the prevention and treatment of multidrug-resistant bacterial infections.

Objective:To investigate the changes of the distribution and drug resistance profile of bacteria from ICU children with lower respiratory tract infection (LRTI) in Suzhou City, Jiangsu Province from 2017 to 2022.Methods:From January 2017 to December 2022, a cross-sectional observational study on the bacterial spectrum analysis among intensive care unit (ICU) children with LRTI was conducted in Children′s Hospital of Soochow University. The bacteria was cultivated by culture methods from sputum samples, and identified by MALDI-TOF mass spectrometry. Drug sensitivity tests were performed by the VITEK2 Compact fully automated analysis system and the paper slide method. The χ2 test or Fisher′s exact probability was used to analyze the changes of the distribution of sputum culture-positive bacteria and drug resistance in ICU children. Results:The overall detection rate of sputum culture was 42.06% (1 182/2 810). Staphylococcus aureus (25.63%,303/1 182), Acinetobacter baumannii (13.62%,161/1 182) and Haemaphilus influenzae (13.28%,157/1 182) were the top three. Proportions of Acinetobacter baumannii (17.90% vs. 11.02%, χ2=11.17, P=0.001), especially carbapenem-resistant Acinetobacter baumannii (43.70% vs. 23.50%, χ2=15.21, P<0.001) increased significantly from 2020 to 2022. However, the proportions of Haemophilus influenzae (8.50% vs. 16.19%, χ2=14.27, P<0.001), Streptococcus pneumoniae (8.50% vs. 15.92%, χ2=13.42, P<0.001) and extended-spectrum-lactamase producing Escherichia coli (8.89% vs. 18.00%, χ2=5.45, P=0.025) decreased. Drug resistant results showed that Acinetobacter baumannii was obviously more resistant to imipenem ( χ2=4.43, P=0.035) and levofloxacin ( χ2=12.53, P<0.001), while more sensitive to minocycline ( χ2=8.34, P=0.004). Escherichia coli showed a significant increase in resistance to piperacillin tazobactam ( χ2=8.29, P=0.008) and cefoperazone sulbactam ( χ2=5.07, P=0.024) from 2020 to 2022; Klebsiella pneumoniae consistently maintained a resistance rate of more than 60% to first and second-generation cephalosporins, and remain susceptible to quinolones and carbapenems. Staphylococcus aureus remained highly susceptible to levofloxacin (drug resistance rate: 2.31%,7/303) and sulfamethoxazole/trimethoprim (drug resistance rate: 4.95%,15/303) from 2020 to 2022. Conclusion:Higher detection and resistance rates of Acinetobacter baumannii from sputum culture in ICU children from 2020 to 2022 were explored. Resistance of Escherichia coli to β-lactamase inhibitor combinations was more serious. Regular monitoring the changes of the etiology of respiratory tract infections in ICU Children is particularly important for the prevention and treatment of multidrug-resistant bacterial infections.

Objective:To observe the inhibitory effect of dobutamine on proliferation of FLT3-ITD mutated acute myeloid leukemia(AML)cells and explore the feasibility of dobutamine as a monotherapy or in combination with quizartinib for the treatment of this type of AML.Methods:FLT3-ITD mutant cell lines MOLM13 and MV4-11 were cultured in vitro and divided into control group,dobutamine treatment group,quizartinib treatment group,and dobutamine combined with quizartinib treatment group.Cell viability,ROS levels,and apoptosis rate were detected by CCK-8,Flow cytometry,respectively,as well as the expression of YAP1 protein by Western blot.Results:Both dobutamine and quizartinib inhibited the proliferation of FLT3-ITD mutant AML cell lines.Compared with the control group,the dobutamine group exhibited a significant increase in ROS levels(P＜0.01),an increase in apoptosis rates(P＜0.05),and a decrease in YAP1 protein expression(P＜0.05).Compared with the dobutamine group,the combination of quizartinib and dobutamine significantly reduced cell viability(P＜0.05),increased ROS levels(P＜0.01),and decreased YAP1 expression(P＜0.05).Conclusion:Dobutamine as a monotherapy can inhibit the proliferation of FLT3-ITD mutated AML cells,inducing apoptosis.Additionally,the combination of quizartinib enhances the targeted inhibitory effect on FLT3-ITD mutated AML.The mechanism may involve the inhibition of YAP1 protein expression in AML cells of this type,leading to an increase in ROS levels and exerting its anti-tumor effects.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective To explore the overall level,distribution characteristics,and differences in household fine particulate matter (PM_2.5) pollution caused by fuel burning in urban and rural areas in China. Methods The relevant articles published from 1991 to 2021 were retrieved and included in this study.The data including the average concentration of household PM_2.5 and urban and rural areas were extracted,and the stoves and fuel types were reclassified.The average concentration of PM_2.5 in different areas was calculated and analyzed by nonparametric test. Results The average household PM_2.5 concentration in China was (178.81±249.91) μg/m³.The mean household PM_2.5 concentration was higher in rural areas than in urban areas[(206.08±279.40) μg/m³ vs. (110.63±131.16) μg/m³;Z=-5.45,P<0.001] and higher in northern areas than in southern areas[(224.27±301.66) μg/m³ vs.(130.11±140.61) μg/m³;Z=-2.38,P=0.017].The north-south difference in household PM_2.5 concentration was more significant in rural areas than in urban areas[(324.19±367.94) μg/m³ vs.(141.20±151.05) μg/m³,χ²=-5.06,P<0.001].The PM_2.5 pollution level showed differences between urban and rural households using different fuel types (χ²=92.85,P<0.001),stove types (χ²=74.42,P<0.001),and whether they were heating (Z=-4.43,P<0.001).Specifically,rural households mainly used solid fuels (manure,charcoal,coal) and traditional or improved stoves,while urban households mainly used clean fuels (gas) and clean stoves.The PM_2.5 concentrations in heated households were higher than those in non-heated households in both rural and urban areas (Z=-4.43,P<0.001). Conclusions The household PM_2.5 pollution caused by fuel combustion in China remains a high level.The PM_2.5 concentration shows a significant difference between urban and rural households,and the PM_2.5 pollution is more serious in rural households.The difference in the household PM_2.5 concentration between urban and rural areas is more significant in northern China.PM_2.5 pollution in the households using solid fuel,traditional stoves,and heating is serious,and thus targeted measures should be taken to control PM_2.5 pollution in these households.
Humans ; Particulate Matter/analysis* ; Air Pollution, Indoor/analysis* ; Cooking ; Environmental Exposure/analysis* ; China ; Rural Population