Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty(THA)and its influence on clinical outcomes.Methods A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system(AI-HIP group),including 16 males and 20 females,aged from 43 to 81 years old with an average of(62.2±10.9)years old.According to the matching principle,36 patients who were planned by the traditional template method at the same period were selected as the control group,including 16 males and 20 females,aged from 40 to 80 years old with an average of(60.9±12.1)years old.The accuracy between two groups of prostheses were compared,as well as the combined eccentricity difference between preoperative planning and postoperative practice,lower limb length difference,osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect.Harris score and visual analogue scale(VAS)were used to evaluate clinical efficacy.Results Both groups were followed up for 12 to 18 months with an average of(14.5±2.1)months.The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2％,100％,58.3％,88.9％,respectively,which were better than 44.4％,83.3％,33.3％,66.7％in control group(P＜0.05).There was no statistical significance in planning of femoral head prosthesis size(P＞0.05).The actual combined eccentricity difference and combined eccentricity difference(practical-planning)in Al-HIP group were 1.0(0.2,2.4)mm and 1.1(-2.1,3.2)mm,respectively;which were better than 3.0(1.4,4.9)mm and 3.5(-1.6,6.5)mm in control group(P＜0.05).There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter(P＞0.05).In AI-HIP group,the actual difference of lower extremity length after surgery,the difference of lower extremity length(practical-planning),osteotomy height from the upper margin of lesser trochanter(practical-planning),actual topshoulder distance after surgery,and topshoulder distance(practical-planning)were 1.5(0.2,2.8),1.1(-0.3,2.2),2.1(-2.3,4.1),(15.3±4.1),2.2(-4.8,0.3)mm,respectively;which were better than control group of 2.6(1.3,4.1),2.5(0.3,3.8),5.8(-2.4,7.7),(13.0±4.3),-5.7(-9.4,-2.2)mm(P＜0.05).At final follow-up,there were no significant differences in Harris scores of pain,function,deformity,total scores and VAS between two groups(P＞0.05).The range of motion score was 4.8±0.6 in AI-HIP group,which was higher than that in control group(4.4±0.8)(P＜0.05).Conclusion Compared with traditional template planning,AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk,restor-ing joint eccentricity,planning lower limb length,osteotomy height and top shoulder distance on the first unilateral THA,and the clinical follow-up effect is satisfactory.

Objective:To investigate the impact of early removal of nasogastric tubes on functional recovery after total gastrectomy for gastric cancer patients, to provide scientific evidence for enhanced recovery after surgery strategies in gastric cancer.Methods:A retrospective cohort study was conducted on 102 gastric cancer patients who underwent total gastrectomy at Beijing Friendship Hospital affiliated with the Capital Medical University from March 2018 to July 2022. Patients were divided into two groups based on whether the gastric tube was removed within 24 hours post-operation: the early removal group (within 24 hours, 55 patients) and the non-early removal group (beyond 24 hours, 47 patients). The recovery outcomes, including time to first flatus, time to fluid intake, length of hospital stay, and the incidence of postoperative complications, were compared between the two groups. Non-normally distributed data were expressed as M( Q1, Q3) and compared using the Wilcoxon rank-sum test. Categorical data were expressed as frequencies or percentages and compared using the chi-square test or Fisher′s exact test. To minimize the impact of potential confounders, multivariable linear regression and logistic regression analyses adjusted for propensity scores were further employed to compare quantitative and qualitative data between the groups. Statistical analyses were performed using R software. Results:The exhaust time, water intake time, and hospital stay in the early removal group were 3.0(2.0, 3.5) days, 4.0(3.0, 5.0) days, and 7.0(7.0, 8.0) days, respectively, while those in the non-early removal group were 4.0(3.0, 5.0) days, 6.0(5.0, 7.0) days, and 8.0(7.5, 11.0) days, respectively. Statistically significant differences were observed between the two groups ( P<0.05). However, there was no significant difference in the incidence of postoperative complications between the two groups (5.45% vs 17.02%, P=0.060). Propensity score-adjusted regression analysis suggested that early tube removal might reduce the risk of postoperative complications ( P=0.042). Conclusion:Early removal of nasogastric tubes can significantly accelerate functional recovery after total gastrectomy for gastric cancer patients and may reduce the risk of postoperative complications, providing important clinical guidance for enhanced recovery after surgery management in gastric cancer.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Animals ; Rats ; Diabetes Mellitus ; Vascular Endothelial Growth Factor A

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Chromatography, Liquid ; Interleukin-6 ; Tandem Mass Spectrometry ; Acupuncture Points ; Arthritis, Rheumatoid/drug therapy*