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 explore the effect of UBE2I and FCGR1A gene expressions on the incidence of acquired immune deficiency syndrome(AIDS)combined with active pulmonary tuberculosis(APTB),so as to provide basis for disease monitoring.Methods A total of 98 AIDS patients combined with APTB and 84 AIDS patients combined with latent tuberculosis infection(LTBI)were selected from the validated whole genome transcriptome dataset(GSE37250).The top 30 differentially expressed genes(DEGs)in the two groups of patients were screened.We established the PPI interaction network,transcription factor-differentially expressed gene(TF-DEG),DEG-miRNA,and environmental chemical regulation network of the top 30 DEGs.Receiver operating characteristic(ROC)curves of 11 key DEGs were plotted and Logistic regression analysis was performed.Results There were 6 054 DEGs in the two groups of patients,and UBE2I was an important core node of the PPI interaction network.FCGR1A had the best predictive and indicative ability for AIDS combined with APTB.Univariate Logistic regression showed that high expressions of UBE2I and FCGR1A were risk factors for AIDS combined with APTB(P＜0.05).The regulatory network showed that VEGFB was a key gene in the TF-DEG network,participating in regulation with transcription factors such as SEPT9 and SMAD5.It targeted miRNAs such as hsa-mir-17-5p and hsa-mir-20a-5p,and was affected by environmental chemicals such as valproic acid and copper sulfate.Conclusion VEGFB plays an important role in the pathogenesis of AIDS combined with APTB.The abnormally high expressions of UBE2I and FCGR1A are associated with the disease progression of AIDS combined with APTB.The disease condition can be monitored by detecting the expression level of UBE2I and FCGR1A.

This research aimed to explore strategies to enhance the influence of major themed publicity in hospital party building within several prominent tertiary public hospitals in China,including one in Beijing,one in Zhejiang and four in Guang-dong.An analysis of themed publicity initiatives over the past five years,particularly during pivotal party events and key thematic activities,was undertaken.This assessment included both offline events and the online media coverage through various integrated media platforms.The study aimed to offer development suggestions for hospitals to amplify the influence of their major themed publicity strategies for Party building.Currently,hospitals are placing increased emphasis on the strategic planning of major themed publicity for Party building.Innovation in content and promotional tactics,along with strengthened integration with main-stream media,is essential.Effective dissemination that elicits empathy and presents high-quality publicity materials is crucial for achieving optimal dissemination outcomes and further elevating the hospital's Party building influence.

Objective To explore the effects of prohibitin 2(PHB2)on sensitivity of non-small cell lung cancer cell line A549 to erlotinib(Erl)and its potential mechanisms.Methods RACK1-specific small interfering RNA was transfected in A549 cells for knocking-down of PHB2.The effects of PHB2 inhibition on cell proliferation and apop-tosis induced by Erl were observed.The colocalization of microtuble-associated protein light chain 3 alpha(LC3)and mitochondria was visualized by MitoTracker staining and green fluorescent protein-microtuble-associated protein light chain 3 alpha(GFP-LC3)transfection.Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine(EdU)staining.Cell colony formation was evaluated by colony forming assay.Apoptotic index of A549 cells was evaluated by TUNEL.Western blot was used to measure the expressions of PHB2 and LC3Ⅱ.Mitochondrial transmembrane potential,cytochrome c and respiratory chain complexⅠ/Ⅱ/Ⅴactivity were analyzed by the commercially availa-ble kits.Results Compared with the siPHB2 and siCtrl+Erl group,the EdU-positive A549 cells and the number of cell colonies decreased significantly(P＜0.05),while the TUNEL-positive A549 cells increased significantly(P＜0.05)in the siPHB2+Erl group.In addition,compared with the siPHB2 and siCtrl+Erl group,mitochondrial transmembrane potential and respiratory chain complexⅠ/Ⅱ/Ⅴactivity decreased significantly(all P＜0.05)and the levels of cytochrome c increased in mitochondrial fractions(P＜0.05)and decreased in cytosolic fractions(P＜0.05)in the siPHB2+Erl group.Conclusions PHB2 inhibition significantly improves sensitivity of A549 cells to Erl,which may be explained by inhibition of PHB2-mediated mitochondrial autophagy.

ObjectiveTo investigate a suspected outbreak of carbapenem-resistant Acinetobacter baumannii （CRAB） nosocomial infection in an intensive care unit （ICU） and provide scientific evidence for prevention and control of multi-drug resistant nosocomial infection. MethodsClinical and epidemiological data of 4 patients with CRAB infection were retrospectively investigated in the ICU of Renji Hospital in November 2021. Environmental hygiene monitoring and multilocus sequence typing （MLST） were conducted and intervention measures were taken. ResultsA total of 4 cases with CRAB infection were identified， among which 1 case was determined to be community-acquired and3 cases were hospital-acquired. The isolated strains shared the same drug resistance， and were all classified into ST368 type. In the surface and hand samples （n=40）， 2 CRAB strains were detected in the air filter beside the bed of the first case， with a detection rate of 5%. After adopting comprehensive prevention and control strategies， including environmental cleaning and disinfection， hand hygiene， staff management and training， and supervision， no similar case with CRAB infection was found. ConclusionThis suspected outbreak of CRAB nosocomial infection may be induced by inadequate environmental cleaning and disinfection， and inadequate implementation of hand hygiene. Timely identification， investigation， and targeted measures remain crucial to effective control of possible nosocomial infection.

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.

In order to solve the problem of high incidence of work-related musculoskeletal disorders (WMSDs) in upper limb lifting workers, a wearable auxiliary device which could be used in upper limb lifting operation was designed. The auxiliary device could be used in upper limb lifting through torsion spring device to reduce the tension of the arm muscles. The back bracket could be adjusted to adapt to the wearers of different height. The 3D model of the auxiliary device was constructed by using SoildWorks software. And the relative position and constraint between the auxiliary device and the digital simulation human were adjusted by using Jack as the main simulation tool. And then the virtual model of upper limb lifting were simulated and analyzed. Through the comparison of Rapid Upper Limb Assessment (RULA) scale, Krist comfort score and simulation results of two-handed reachable domain before and after wearing the auxiliary device, which proved that the wearable auxiliary device could reduce the risk of WMSDs in upper limb lifting workers.

Objective:To observe the application effect of simulation medicine teaching in clinical practice teaching of respiratory department.Methods:A total of 96 five-year undergraduate students of clinical medicine specialty from Batch 2018 were randomized into in two groups in average. The traditional teaching group conducted bedside teaching according to traditional teaching outline, and the simulation medicine group used simulated medical teaching method. The performances of theoretical knowledge and skill operations and the teaching satisfaction with the department were evaluated between the two groups. SPSS 22.0 was used for t test and chi-square test. Results:There was no significant difference in theoretical knowledge between the two groups, but the results of skill operation test and satisfaction with the department of the simulation medicine group were significantly better than those of the traditional teaching group, and the difference was statistically significant [(80.92±5.99) vs. (87.71±4.95), P<0.050; χ2=26.14, P<0.05]. Conclusion:Simulation medicine teaching is better than traditional teaching in clinical practice teaching of respiratory department, which can improve students' clinical skills and operation level, cultivate good clinical thinking for students, and improve their learning interests.

In order to solve the problem of high incidence of work-related musculoskeletal disorders (WMSDs) in upper limb lifting workers, a wearable auxiliary device which could be used in upper limb lifting operation was designed. The auxiliary device could be used in upper limb lifting through torsion spring device to reduce the tension of the arm muscles. The back bracket could be adjusted to adapt to the wearers of different height. The 3D model of the auxiliary device was constructed by using SoildWorks software. And the relative position and constraint between the auxiliary device and the digital simulation human were adjusted by using Jack as the main simulation tool. And then the virtual model of upper limb lifting were simulated and analyzed. Through the comparison of Rapid Upper Limb Assessment (RULA) scale, Krist comfort score and simulation results of two-handed reachable domain before and after wearing the auxiliary device, which proved that the wearable auxiliary device could reduce the risk of WMSDs in upper limb lifting workers.