Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

The activation of the sirtuin1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species (ROS) levels. Clinical trials have demonstrated that Zhongfeng Xingnao Liquid (ZFXN) ameliorates post-stroke cognitive impairment (PSCI). However, the underlying mechanism, particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway, remains unclear. This study employed an oxygen-glucose deprivation (OGD) cell model using SH-SY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation (2VO). The effects of ZFXN on learning and memory, neuroprotective activity, mitochondrial function, oxidative stress, and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro. Results indicated that ZFXN significantly increased the B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax) ratio, reduced terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL)⁺ cells, and markedly improved cognition, synaptic plasticity, and neuronal function in the hippocampus and cortex. Furthermore, ZFXN exhibited potent antioxidant activity, evidenced by decreased ROS and malondialdehyde (MDA) content and increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels. ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential (MMP), Tom20 fluorescence intensity, adenosine triphosphate (ATP) and energy charge (EC) levels, and mitochondrial complex I and III activity, thereby inhibiting mitochondrial damage. Additionally, ZFXN significantly increased SIRT1 activity and elevated SIRT1, nuclear Nrf2, and HO-1 levels. Notably, these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro. In conclusion, ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
Sirtuin 1/genetics* ; Animals ; NF-E2-Related Factor 2/genetics* ; Cognitive Dysfunction/genetics* ; Male ; Rats, Sprague-Dawley ; Rats ; Humans ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Heme Oxygenase-1/genetics* ; Stroke/complications* ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Neuroprotective Agents

Objective To establish a novel real-time quality control method for rapidly identifying the random error of sodium ion con-centration in serum using an artificial intelligence voting algorithm,and evaluate the relevant effectiveness of the model established on this basis.Methods A total of 144 754 test results of serum sodium ion rom the inpatients measured by Beckman AU5400 biochemis-try analyzer from January to May 2021 were obtained retrospectively from laboratory information system of the Department of Clinical La-boratory,Nanjing Drum Tower Hospital,and all the data were used as unbiased data for the current study.The random errors were arti-ficially introduced to generate the corresponding biased data set.Subsequently,the voting algorithm-based internal quality control model(ViQC)was established using the principles of the voting algorithm.The ViQC model and five classical PBRTQC(patient-based real-time quality control)algorithms were performed direct to each biased data.The analytical performance of the ViQC model was evaluated by using classification model criteria.The trimmed average number of patient samples until error detection(tANPed)was used to com-pare the clinical detection efficacy of the ViQC model with those of the five classical algorithms,and the error detection curves were plotted.Results Compare with all the classical algorithms,the ViQC model showed a false positive rate below 0.002 and achieved ac-curacy above 0.951 in detecting all the deviations.When the error factors were 1.5,2.5,and 3.0,the false positive rate of the ViQC model was zero.When the error factor was 2.5,its accuracy reached 0.979.Compared to the five classical PBRTQC algorithms,the ViQC model reduced the overall average tANPed by up to 34％and showed higher sensitivity for error detection.In addition,the ViQC model demonstrated the area under the ROC curve was as high as 0.989 at TEa on the test set,but the value of tANPed wasonly five.Conclusion We successfully established a real-time quality control model for the data of patients based on artificial intelligence algo-rithms,and its efficacy of clinical detection was superior to the traditional PBRTQC algorithms.

Objective To establish U251 cells with inhibited expression of interferon-γ inducible protein 30 (IFI30), and to investigate the effect of IFI30 on cell biological function as well as its underlying mechanism. Methods Three knockdown sequences which target IFI30 were designed online and 3 small interfering RNAs (siRNA) were synthesized. After transfection, the inhibition efficiency was detected by real-time quantitative PCR. The siRNA sequence with the highest inhibition efficiency was selected to create short hairpin RNA (shRNA) plasmids. The recombinant plasmids and packaging plasmids were co-transfected into HEK293T cells to prepare lentivirus. The glioma U251 cells were transfected with lentivirus, and the positive cells were screened by puromycin. CCK-8 assay, 5-ethyl-2'-deoxyuridine (EdU) and colony formation assays were used to analyze cell proliferation; the flow cytometry was used to analyze cell cycle and apoptosis; the Transwell^TM assay was used to detect cell invasion; the wound-healing assay was employed to detect cell migration, and western blot analysis to detect the protein expresison of cyclin D1, B-cell lymphoma factor 2 (Bcl2), epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), signal transducer and activator of transcription 1 (STAT1). Results The sequence which effectively target IFI30 was screened and U251 cell line capable of inhibiting the IFI30 expression was successfully established. When IFI30 expression was knocked down, the proliferation of U251 cells was inhibited, along with increased ratio of cells in the phase G0/G1, the decreased phase S, the increased rate of cell apoptosis. The cell invasion and migration capabilities was also reduced. The decreased expression of cyclin D1, Bcl2 and N-cadherin were observed in U251 cells, and the expression of E-cadherin and the phosphorylation of STAT1 were found increased. Conclusion Knockdown of IFI30 inhibits the proliferation, invasion and migration of human glioma cell U251 and promotes its apoptosis by activating STAT1.
Humans ; Cyclin D1/genetics* ; HEK293 Cells ; Interferon-gamma ; RNA, Small Interfering ; Apoptosis/genetics* ; Cadherins ; Cell Proliferation/genetics* ; Glioma/genetics* ; Proto-Oncogene Proteins c-bcl-2 ; Oxidoreductases Acting on Sulfur Group Donors ; STAT1 Transcription Factor/genetics*

Objective: To explore the association between bedroom light at night (LAN) exposure and body mass index (BMI) in children at 1 year follow up, so as to provide new strategies for obesity prevention. Methods: From December 2021 to May 2022, cluster random sampling was conducted, involving 648 children from two primary schools in Tianchang, Chuzhou City, Anhui Province, China, to assess bedroom LAN exposure of children during sleep. A questionnaire survey and physical examination were carried out in May 2022. Multivariate linear regression was performed to analyze the correlation between bedroom LAN exposure and BMI variable quantity at 1 year follow up (May, 2023). Results: The median intensity of bedroom LAN exposure during the sleep episode was [1.11(0.35,3.24)lx] in children. The proportion of the sample exposed to an average light intensity of ≥3 lx was 27.5%, while 19.0% was exposed to a LAN intensity of ≥5 lx during the sleep episode. In the multivariable linear regression, after adjusting for covariates, including sex, baseline age, sleep duration, family monthly income, and maternal education level, exposure to a 1 h-average post bedtime LAN intensity of ≥3 lx ( β=0.25, 95%CI =0.05-0.44) and LAN≥5 lx ( β=0.34, 95% CI = 0.12-0.55) was associated with a gain of 0.25 and 0.34 kg/m 2, respectively, in the children s BMI at the 1 year follow up ( P < 0.05). Conclusions A positive correlation was found between bedroom LAN exposure and BMI variable quantity at 1 year follow up in children. Thus, reduced bedroom LAN exposure might be useful for interventions aimed at obesity prevention.

Objective:To survey the status quo of family doctor work mode in Shanghai Xuhui district.Methods:Semi-structured and structured in-depth interviews were conducted in Shanghai Xuhui district from April to June 2021, 11 directors, 12 deputy directors in charge and 30 family doctors from 12 community health service centers participated in the survey and completed two stages and four sessions of interviews on the development of the integrated and high-quality family doctor work mode and the ways to realize and the challenges to face. The records of interviews were transcribed, sorted and analyzed using the Colaizzi 7-step analysis method.Results:The survey showed that the family doctor contracting was carried out in a large team mode in the whole district, mainly for the elderly, and most of contracted residents were not included in health management and follow-up services. The team was composed of family doctors and assistants, and the routine outpatient service was the main work pattern, and the regular services also included the chronic disease follow-up and health check-up for elderly. On the issue of how to output high-quality integrated services, the majority of doctors (12/13) believed that the contracted individual should be taken as the unit of fine service, carrying out overall health assessment, optimizing medication plan, lifestyle guidance, one-stop service in hospital, etc.; only one doctor suggested that the family should be the management unit. For upgrading the working mode and service quality, insufficient time and energy were the main obstacle. Public health work occupied a lot of working time, but it seemed not be transformed into favorable resources and conveniences in health management and services. The professional assistants should carry out some responsibility to save family doctor′s time. The survey suggests that informatization, service space, and sufficient drug supply are the keys for ensuring high-quality and high-efficiency integrated services.Conclusion:The organizational structure of the family doctor team in Shanghai Xuhui district is relatively mature, but the integrated and high-quality service output has not yet reached. It is necessary to make regional overall planning and increase efforts to achieve the integration of medical treatment and prevention, so as to gain time for family doctors to carry out high-quality services. At the same time, it is also necessary to cultivate effective family doctor assistants, provide an information work platform that matches the work attributes and goals of family doctors, open up an integrated health management service space, and ensure the full range supply of drugs.

Objective:To observe the effects of sacubitril/valsartan (LCZ696) on viral replication and cardiomyocyte apoptosis in mice with coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) and to analyze the underlying mechanisms.Methods:Forty BALB/c mice were randomly divided into four groups with 10 in each group: Sham, Sham+ LCZ696, VMC, and VMC+ LCZ696 groups. VMC model was established by intraperitoneal injection of 0.1 ml of CVB3 with a concentration of 10 6 TCID 50/ml into BALB/c mice, while the sham intervention was an equal volume of saline. The day of virus injection was defined as day 0. LCZ696 was administered by gavage at a dose of 60 mg/kg every day for seven consecutive days starting from day 1. Mouse survival rates were calculated. Echocardiography was used to evaluate the cardiac function of mice. The level of creatine kinase-MB (CK-MB) was detected by ELISA. Western blot was used to detect the levels of inflammatory cytokines (IL-6, TNF-α), apoptosis-related proteins (caspase-3, cleaved-caspase-3, Bax, Bcl-2), CVB3 surface protein (VP-1) and p-AKT/AKT in the hearts of mice. CVB3 mRNA in mouse hearts was measured by PCR. Inflammatory cell infiltration and cell apoptosis in mouse hearts were observed by HE staining and TUNEL staining, respectively. Results:Compared with the Sham group, the mice in the VMC group had a decreased survival rate and impaired cardiac function ( P<0.05). The levels of CK-MB, IL-6, TNF-α, cleaved-caspase-3/caspase-3, Bax/Bcl-2, VP-1, and CVB3 mRNA in the hearts of VMC mice increased significantly ( P<0.05), accompanied by increased expression of AKT, decreased phosphorylation of AKT ( P<0.05) and increased cell apoptosis. LCZ696 reversed the above changes. It could increase the survival rate, improve the cardiac function ( P<0.05), decrease cardiac inflammation, cell apoptosis and viral replication ( P<0.05), and increase the phosphorylation of AKT ( P<0.05). LCZ696 had no significant effects on the survival rate, cardiac function, myocardial injury, cardiac inflammation, cell apoptosis, viral replication or the expression of PI3K/AKT signaling pathway-related proteins in normal mice. Conclusions:LCZ696 could significantly inhibit cardiomyocyte apoptosis and reduce CVB3 replication in the hearts of VMC mice by regulating the PI3K/AKT pathway, thereby improving mouse cardiac function and survival rate.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.