Human exhaled breath has great application prospects,e.g.,monitoring pharmacokinetics,disease diagnosis,due to its advantages such as non-invasive and high-frequency sampling.Breath samples can be collected from the oral and nasal cavity.However,the oral and nasal environment affect the chemical composition of breath sample.Therefore,the investigation on the chemical composition of mouth-exhaled breath and nose-exhaled breath is crucial for selection of appropriate sampling strategy for individual studies.In this work,secondary electrospray ionization-high resolution mass spectrometry(SESI-HRMS)was applied to analysis of respiratory metabolomics in real time.A quantitative analysis approach was established for 9 kinds of volatile organic compounds(VOCs)e.g.2-butanone,2-pentanone,ethyl acetate,methyl methacrylate,toluene,styrene,mesitylene,isoprene and limonene.The limit of detection was 2.3?240.8 ng/m3.The intra-day(n=6)and inter-day(n=18)relative standard deviations were 0.6%?4.6%and 4.3%?12.2%,respectively.Nine healthy subjects were recruited to investigate the chemical composition of mouth-exhaled and nose-exhaled breath.The results showed the good performance in quantitative analysis of 9 VOCs in breath air.It was found that the number of unique component(m/z)detected in mouth-exhaled breath(167)was 2.2 times greater than that detected in nose-exhaled breath(76),which might result from the complex environment in oral cavity.The signal intensity of commun component(163)was significantly different between mouth-exhaled breath and nose-exhaled breath.Additionally,the elemental composition analysis showed that the proportion of polar compounds detected in nose-exhaled breath was higher than that in mouth-exhaled breath.This study demonstrated that there was significant differences in the chemical composition between mouth-exhaled and nose-exhaled breath,which provided a theoretical basis for selection of exhalation mode.

Objective To investigate the clinical application of perioperative human serum albumin(HSA)in cardiac surgery in multiple regions in China,and to evaluate the rationality of its clinical application in conjunction with the clinical guidelines,in order to provide a reference for promoting the rational application of HSA.Methods The medical records of patients who underwent cardiac surgery from April to June 2019 in eight hospitals across the country were retrospectively collected.The statistical information on patients'general information,the dosage,course of treatment,and cost of HSA,and the serum albumin level before and after medication was analyzed to evaluate the use of HSA.Relevant evaluation criteria were established,and the rationality of its medication was evaluated.Results Data from a total of 449 patients were included for analysis,the appropriate rate of medication was 81.1％.The course of medication was mostly＞2-5 days and the total amount of HSA was mostly 50-99 g.The main purpose of medicaiton were improving colloid osmotic pressure,reducing exudation to improve interstitial edema,postoperative volume expansion.Conclusion Clinical attention should be paid to ensure the rational application of HSA in cardiac surgery during the perioperative period and prevent the abuse of blood products.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Attenuated Salmonella typhimurium VNP20009 is a widely used natural oncolytic bacterium, which has great application potential given its unique characteristics, including clinical safety, tumor targeting specificity, and explicit genome sequence. Here, we show that tumor progression can be effectively reduced by intraperitoneal administration with VNP20009 in a mouse model of melanoma (all animal experiments were conducted in accordance with the Animal Ethics Committee of China Pharmaceutical University); co-culture experiment in vitro demonstrated that VNP20009 can induce the polarization of macrophage M1, accompanied by expression of inflammation-related factors; flow cytometry analysis showed that VNP20009 induced the increase of immune cell infiltration in tumor. Further analysis showed that T cells infiltration in tumor-draining lymph node (TDLN) increased, and VNP20009 induced the activation of CD4⁺ T cells and CD8⁺ T cells in tumor. Our results demonstrate that VNP20009 treatment significantly inhibited melanoma tumors by remodeling tumor-associated macrophages to an M1-like phenotype, as well as recruiting and activating cytotoxic T cells, combined with its own antigenic activity to exert anti-tumor immunity.

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

Objective:To establish and validate a risk prediction model of disseminated intravascular coagulation (DIC) by the screening independent risk factors for the occurrence of DIC in patients with electrical burns.Methods:The retrospective case series study was conducted. The clinical data of 218 electrical burn patients admitted to Baogang Hospital of Inner Mongolia from January 2015 to January 2023 who met the inclusion criteria were collected, including 198 males and 20 females, with the age of (38±14) years. The patients were divided into DIC group and non DIC group based on whether they were diagnosed with DIC during the treatment period. The following data of patients of two groups were collected and compared, including age, gender, total burn area, full-thickness burn area, injury voltage, whether osteofascial compartment syndrome occurred within 1 day after injury, duration of stay in burn intensive care unit, total length of hospital stay, whether combined with inhalation injury and multiple injuries, whether shock occurred upon admission, the abbreviated burn severity index score, and the acute physiology and chronic health evaluation Ⅱ score. The laboratory examination data of the patients within 24 hours after admission were also collected, including blood routine indexes: white blood cell count (WBC), hemoglobin level, platelet count (PLT), and neutrophil count; coagulation indexes: activated partial thromboplastin time (APTT), prothrombin time, thrombin time, and levels of D-dimer and fibrinogen (FIB); blood biochemistry indexes: aspartic transaminase, alanine transaminase, direct bilirubin, total bilirubin, total protein, albumin, blood glucose, creatinine, and urea nitrogen; blood gas analysis indexes: blood pH value, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, bicarbonate, and base excess; and cardiac zymogram indexes: levels of myoglobin, troponin, lactate dehydrogenase, creatine kinase (CK), and α-hydroxybutyrate dehydrogenase. Data were statistically analyzed with chi-square test, Fisher's exact probability test, independent sample t test, and Mann-Whitney U test. For the variables with statistically significant differences in single factor analysis, the least absolute value selection and shrinkage operator (LASSO) regression was used to reduce the dimension, and the predictive factors for DIC in 218 patients with electrical burns were screened. The above-mentioned predictors were included in multivariate logistic regression analysis to find out the independent risk factors for DIC in 218 patients with electrical burns, and to draw the prediction model nomograms. The performance of the prediction model was evaluated by the receiver operating characteristic (ROC) curve and the area under the ROC curve, and the prediction model was validated by the calibration curve and clinical decision curve analysis (DCA). Results:Compared with those in non DIC group, the total burn area, full-thickness burn area, total length of hospital stay, and the proportions of high voltage caused injury, occurrence of osteofascial compartment syndrome within 1 day after injury, combination of inhalation injury, and occurrence of shock upon admission of patients in DIC group were significantly increased/prolonged (with Z values of -2.53, -4.65, and -2.10, respectively, with χ2 values of 11.46, 16.00, 7.98, and 18.93, respectively, P<0.05). Compared with those in non DIC group, the APTT, level of D-dimer, myoglobin, WBC, PLT, and levels of FIB, total bilirubin, and CK of patients within 24 hours after admission in DIC group were significantly prolonged/increased (with Z values of -2.02, -4.51, and -3.82, respectively, with t values of -3.84, -2.34, -2.77, -2.70, and -2.61, respectively), and the level of total protein and blood pH value were significantly reduced ( t=-2.85, Z=-2.03), P<0.05. LASSO regression analysis was carried out for the above 17 indicators with statistically significant differences. The results showed that injury voltage, the occurrence of shock upon admission, the occurrence of osteofascial compartment syndrome within 1 day after injury, and levels of D-dimer and total protein within 24 hours after admission were predictive factors for the occurrence of DIC in 218 patients with electrical burns (with regression coefficients of 0.24, 0.52, 0.35, 0.13, and -0.001, respectively). Multivariate logistic regression analysis showed that injury voltage, the occurrence of shock upon admission, the occurrence of osteofascial compartment syndrome within 1 day after injury, and D-dimer level within 24 hours after admission were independent risk factors for DIC in 218 patients with electrical burns (with odds ratios of 3.33, 4.24, 2.68, and 1.38, respectively, with 95% confidence intervals of 1.43-7.79, 1.78-10.07, 1.17-6.13, and 1.19-1.61, respectively, P<0.05). Based on the aforementioned four independent risk factors, the nomogram of prediction model for evaluating the probability of DIC in patients was drawn. The area under the ROC curve of prediction model was 0.88, and the 95% confidence interval was 0.82-0.95, indicating that the model had good predictive ability; the curve of prediction model tended to be near the ideal curve, indicating that the model had a high calibration degree; the clinical DCA of prediction model showed that the threshold probability of patients ranged from 4% to 97%, indicating that the model had good predictive ability. Conclusions:The injury voltage, the occurrence of shock upon admission, the occurrence of osteofascial compartment syndrome within 1 day after injury, and D-dimer level within 24 hours after admission are independent risk factors for the occurrence of DIC in patients with electrical burns. The prediction model established based on the above indicators can provide early warning for the occurrence of DIC in these patients.

Dendritic cells (DCs) are specialized antigen-presenting cells. Immature dendritic cells can be activated into mature dendritic cells by recognizing antigens, then the antigens are processed and pres-ented to T lymphocytes. DCs play a vital role in initiating immune response, regulating immune response and maintaining immune tolerance. Therefore, regulating the immune function of DCs can be used to treat diseases such as autoimmune diseases and tumors. With the deepening of research on the regulation of DCs, people have gradually realized that the existence of reactive oxygen species (ROS) in DCs is of great significance. ROS is a term of strong oxidizing reactive species, and the dynamic balance of its pro-duction and removal is the key to maintaining cell redox homeostasis. ROS of physiological level is an im-portant molecule involved in a variety of signal pathways, which can regulate cell growth, differentiation and different physiological and biochemical reactions. The changes in the level of ROS affect the state and function of cells. In addition, because there are many ways to produce ROS in the cell, the effects of dif-ferent sources of ROS on DCs are not usually the same; and even the same source of ROS may have dif-ferent effects when cells are in different states. This article summarized the influence of intracellular ROS changes and different sources of ROS on the differentiation, maturation and function of DCs, aiming to re-veal how ROS plays an important role in regulating the immune function of DCs. At the same time, this article also showed the urgent need for the in-depth study of ROS regulating the function of DCs, which may help the application of DCs immune regulation to a wider range of disease treatments.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Animals ; Biological Transport, Active/physiology* ; Centrioles/metabolism* ; Cilia/metabolism* ; Mice ; Mice, Mutant Strains ; N-Acetylglucosaminyltransferases/metabolism*