OBJECTIVE: To explore whether microneedle pretreatment can significantly improve the efficacy and safety of 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) in the treatment of oral leukoplakia. METHODS: A non-randomized controlled clinical trial was conducted. Patients with clinical and pathological diagnosis of oral leukoplakia in the Department of Oral Mucosa, Peking University School and Hospital of Stomatology were divided into experimental group and control group. The control group was treated with conventional ALA-PDT, and the experimental group was pretreated with micro- needle buckling under superficial anesthesia with lidocaine before conventional ALA-PDT. The clinical manifestations of the two groups were recorded, the lesion area was measured, the clinical efficacy was evaluated, the number of treatment sessions and treatment unit duration were analyzed, and the pain after treatment was evaluated by visual analogue scale. The above data of the two groups were statistically analyzed. RESULTS: A total of 11 patients were included in the experimental group and 19 patients were included in the control group. The complete remission rate of the experimental group and the control group was 45.5% and 36.8%, the partial remission rate was 54.5% and 57.9%, and the no remission rate was 0% and 5%, respectively. There was no significant difference in the treatment effect between the two groups. Meanwhile, the treatment unit duration of the experimental group and the control group were (9.05±5.74) min/cm² and (21.38±15.44) min/cm², respectively, and the number of treatment sessions were (2.36±0.67) times and (3.58±1.57) times, respectively. These differences between the two groups were statistically significant (t=-3.125, P < 0.05; t=-2.932, P < 0.05). Similarly, multiple linear regression analysis with 7 factors including age, dysplastic pathology, lesion classification, etc., also confirmed that pretreatment could significantly shorten the treatment unit duration (P < 0.05). In addition, there was no significant difference in pain score (visual analogue scale) between the two groups after treatment, and the microneedle puncture pretreatment did not increase the adverse reactions of ALA-PDT treatment. CONCLUSION Microneedle pretreatment followed by conventional ALA-PDT shows a good clinical effect on oral leukoplakia, which can significantly shorten the clinical treatment time, reduce the number of visits, and save medical costs.
Humans ; Photochemotherapy/instrumentation* ; Leukoplakia, Oral/drug therapy* ; Aminolevulinic Acid/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Needles ; Photosensitizing Agents/therapeutic use* ; Aged ; Combined Modality Therapy

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Objective: To investigate the basic situation of pre-analytical quality management in blood station laboratories in North China, and to provide baseline data for promoting the homogenization and standardization of these pre-analytical processes in each blood station laboratory. Methods: A cross-sectional status survey was designed based on the quality management regulations of blood stations, ISO15189 standards and relevant quality management requirements. This survey covering various aspects including laboratory general situation, sample collection and temporary storage, transportation, reception, and quality continuous improvement situations. Data analysis was performed on the survey results of each laboratory. Results: All the 38 blood station laboratories in North China had established a pre-analytical quality management system framework and implemented basic pre-analytical quality control activities; however, there were differences in implementation. 1) Among the 12 basic quality items, 3 items were monitored by all the investigated laboratories (100%), 6 items were monitored by the vast majority of laboratories (about 90%), and 3 items were monitored by a portion of laboratories (about 60%). There were no significant differences in the monitoring index among the three regions and among different types of laboratories (P>0.05). 2) Among the total of 26 items in the three key processes before testing (sample collection and storage, transportation, reception and processing), 12 items were monitored by all laboratories (100%), 11 items were monitored by the vast majority of laboratories (about 90%), and 3 items were monitored by a portion of laboratories (about 75%). There were no significant differences in monitoring index among different regions and types of laboratories (P>0.05). Conclusion: This survey provides a reference and basis for the gap analysis of the pre-analytical process quality management in 38 blood station laboratories across North China. It facilitates laboratories in identifying pre-analytical quality problems, resolving problems, preventing errors, and ensuring that the quality of blood samples before testing meets the established requirements. It lays a foundation for the homogenization of pre-analytical quality management in regional blood stations.

Objective: To determine the frequency and main reasons of unqualified samples by analyzing the quality of pre-analytical samples in blood stations in North China, thereby providing a reference and basis for gap analysis in the implementation of pre-analytical process quality management for participating laboratories and ensuring that only high-standard and high-quality blood samples proceed to testing. Methods: Data on the quality of pre-analytical samples from blood station laboratories in North China was collected via questionnaire. Statistical analysis were performed on: 1) the basic information of samples quality monitoring in the laboratories; 2) the distribution of the overall pre-analytical unqualified rate of samples and the pre-analytical unqualified rate of samples in each laboratory; 3) the distribution of reasons for sample disqualification. Results: 1) The overall pre-analytical unqualified rate of samples in blood station laboratories in North China was 4.55, with a total sigma level of 5.39σ. The 25th, 50th and 75th percentiles (P25, P50, P75) for the total unqualified rate were 0.00, 1.10 and 5.96, respectively. The corresponding percentiles for the Sigma level were 5.34σ, 5.71σ, and 6.00σ, respectively. The pre-analytical unqualified rate of serological and nucleic acid samples (4.89 vs 4.22) showed a significant difference (χ =9.575, P<0.05). 2) The average unqualified rate of samples in region A, B and C was 1.71, 9.50 and 12.64 (χ =1 590.721, P<0.05), and the sigma level was 5.66σ, 5.21σ and 5.16σ, respectively. 3) The main reasons for unqualified serological samples were chylous blood (72.65%), hemolysis (17.39%), abnormal hematocrit (5.80%), and insufficient volume (3.50%). The main reasons for the unqualified nucleic acid samples were chylous blood (78.26%), hemolysis (8.84%), failure to centrifuge as required (5.01%), abnormal hematocrit (4.66%), and insufficient volume (1.92%). Conclusion: In North China, the quality indicators for the pre-analytical processes in blood station laboratories are generally well-managed. Laboratories in region A outperformed the national average in pre-analytical specimen quality control. However, participating laboratories exhibit gaps in implementing pre-analytical quality management. Through effective analysis of pre-analytical process quality metrics and inter-laboratory comparisons, laboratories can identify discrepancies and address shortcomings. By establishing clear quality objectives, they can achieve continuous improvement and ensure the validity of test results.

Objective: To investigate the assessment criteria and subsequent handling practices of hemolytic and lipemic blood samples before testing in blood screening laboratories in North China, and to provide data to support the standardization of their management in blood station laboratories. Methods: Data on the preanalytical management of hemolytic and lipemic samples from 38 laboratories were collected. The details of management on the criteria and verificatioon for assessment, the assessment methods, and subsequent handling procedures of hemolytic and lipemic samples in blood station laboratories were analyzed. Results: 1) All 38 blood station laboratories monitored serological and nucleic acid samples for hemolysis and lipemia in pre-analytical phase. 2) The criteria and methods for assessing hemolytic and lipemic samples varied among the laboratories of the 38 blood stations. 15 laboratories (39.47%) followed manufacturer's instructions, 9 laboratories (23.68%) formulated their own criteria, and 14 laboratories (36.84%) referred to the criteria of other laboratories. 16 laboratories (42.11%) verified the criteria for assessing hemolytic and lipemic samples, with significant variations in verification rate across laboratories from different regions (P<0.05). For the assessment methods, visual inspection was used by 28 laboratories (73.68%) for hemolytic samples and by 27 laboratories (71.05%) for lipemic samples; the colorimetric card method was used by 10 laboratories (26.32%) for assessing both hemolytic and lipemic samples; the instrumental method was used by 1 laboratory (2.63%) for assessing lipemic samples.3) The handling procedures for hemolytic and lipemic samples varied significantly and followed a gradient distribution pattern among 38 laboratories (including accepting samples for testing, accepting samples for concession testing, re-collecting samples, and rejecting samples and halting testing). With increasing severity of hemolysis and lipemia, more laboratories halted testing, and relatively fewer laboratories accepted samples for normal testing. 5 laboratories (13.16%) applied different handling procedures on serological and nucleic acid samples. Conclusion: This survey provides a reference and basis for analyzing gaps in the management of hemolytic and lipemic samples during the preanalyical phase in blood station laboratories in North China. It enables laboratories to identify the problems and deficiencies in the management of hemolytic and lipemic samples, to ensure preanalytical samples quality meets the established requirements, and to lay a foundation for promoting the homogenization and standardization of the regional sample quality management mode.

Objective To assess the impact of intravenous esketamine administered prior to car-diopulmonary bypass(CPB)initiation on ventricular function and internal carotid artery blood flow in pa-tients undergoing heart valve replacement surgery.Methods Sixty patients underwent elective CPB heart valve replacement,38 males and 22 females,aged 18-75 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅱ or Ⅲ,NYHA cardiac function classification Ⅰ-Ⅲ,and a left ventricular ejection fraction(LVEF)of≥45％,were selected.The patients were randomly divided into two groups:esketamine group(group E)and normal saline group(group C),30 patients in each group.Total intravenous anesthesia was used during the operation.Following the initiation of CPB,group E received an intravenous infusion of es-ketamine at a rate of 0.5 mg·kg-1·h-1 until the conclusion of the procedure,while group C received an equivalent volume of normal saline concurrently at the same rate.HR,MAP,CVP,and cardiac output index(CI)were recorded before anesthesia induction,during skin resection,and within 60 minutes after stopping CPB.LVEF,left ventricular global longitudinal strain(GLS),global longitudinal time-to-peak strain standard deviation(GLTSD),global circumferential strain(GCS),global circumferential time-to-peak strain standard deviation(GCTSD),right ventricular ejection fraction(RVEF),right ventricular GLS,and GLTSD were obtained during skin resection,within 40 minutes of CPB,and 60 minutes after stopping CPB.rScO2,BIS,concentrations of Hb and lactic acid(Lac),peak systolic flow velocity(SPV),quantity of flow-internal carotid artery(Q-ICA),and blood flow resistance index(RI)were recorded before anesthesia induction,during skin resection,within 40 minutes of CPB,and within 60 minutes after stopping CPB.Concentrations of cardiac troponin Ⅰ(cTnⅠ),alanine aminotransferase(ALT),creatinine(Cr),and neuron-specific enolase(NSE)were recorded before anesthesia induction and 6 hours after operation.Spon-taneous resuscitation after CPB,postoperative extubation time,duration of ICU stay,total hospital stay,in-cidence of adverse cardiac events,and 30-day postoperative mortality were recorded.Results Compared with group C,group E exhibited a significant increase in CI within 60 minutes after stopping CPB(P＜0.05).The LVEF,RVEF,and right ventricular GLS demonstrated significant increases within 60 minutes after stopping CPB in group E compared with group C(P＜0.05).The left ventricular GLS and left ven-tricular GCTSD displayed significant increases 30 minutes after stopping CPB in group E compared with group C.The RI exhibited a significant increase within 40 minutes of CPB in group E compared with group C(P＜0.05).There were no significant differences in cTnⅠ,ALT,Cr,NSE,spontaneous resuscitation affter CPB,postoperative extubation time,duration of ICU stay,total hospital stay,incidence of cardiac adverse events,and 30-day postoperative mortality between the two groups.Conclusion Administration of esket-amine following the onset of CPB in patients undergoing cardiac surgery demonstrates a significant elevation in CI post-CPB cessation.Furthermore,it may augment ventricular longitudinal strain,thereby enhancing myocardial contraction,leading to increased postoperative ventricular ejection fraction,and sustaining hemo-dynamic stability.

Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.