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 evaluate the correlation between ultrasound parameters of internal carotid artery blood flow and regional cerebral oxygen saturation (rScO 2) in elderly patients undergoing coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Methods:Sixty-four elderly patients undergoing elective CABG under CPB, aged 60-80 yr, regardless of gender, with body mass index of 18.1-28.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, with left ventricular ejection fraction≥50%, were selected. The rScO 2 and ultrasonic parameters of internal carotid artery including peak systolic velocity (PSV-ICA), end-diastolic velocity (EDV-ICA), diameter (D-ICA) and blood flow volume (Q-ICA) were recorded before anesthesia induction (T 0), at surgical skin incision (T 1), at 30 and 60 min of CPB (mean value was calculated, T 2), and at 30 and 60 min after termination of CPB (mean value was calculated, T 3). The ratio of unilateral internal carotid artery blood flow to cardiac output (Q/CO) was calculated. The receiver operating characteristic curve was used to analyze the accuracy of ultrasound parameters of internal carotid artery blood flow in predicting rScO 2 < 60%. Results:PSV-ICA was positively correlated with rScO 2 at T 0, T 1 and T 3 ( P<0.05), but no correlation was found between PSV-ICA and rScO 2 at T 2 ( P>0.05). There was no correlation between EDV-ICA and rScO 2 at each time point ( P>0.05). Q-ICA was positively correlated with rScO 2 at each time point ( P<0.05). Q/CO was not correlated with rScO 2 at T 1 ( P>0.05), but Q/CO was positively correlated with rScO 2 at T 2 and T 3 ( P<0.05). During the non-CPB period (T 0, T 1, T 3), the cutoff values of PSV-ICA and Q-ICA in predicting rScO 2< 60% were 51.35 cm/s and 283.5 ml/min respectively, the sensitivity was 0.900 and 0.900 respectively, and the specificity was 0.610 and 0.857 respectively (AUC=0.761, P=0.006; AUC=0.903, P< 0.001). During the CPB period, the cutoff values of Q-ICA and Q/CO in predicting rScO 2<60% were 296.5 ml/min and 5.84% respectively, the sensitivity was 0.900 and 0.800, and the specificity was 0.545 and 0.659 (AUC=0.764, P=0.001; AUC=0.748, P=0.002), respectively. Conclusions:PSV-ICA and Q-ICA are positively correlated with rScO 2 during the non-CPB period, and Q-ICA and Q/CO are positively correlated with rScO 2 during the CPB period in elderly patients undergoing CABG. PSV-ICA, Q-ICA and Q/CO can accurately predict rScO 2<60%.

ObjectiveTo understand the awareness of knowledge about chronic obstructive pulmonary disease （COPD） and influencing factors among residents in Yangpu District， Shanghai. MethodsWe used cluster random sampling method to conduct face-to-face questionnaire surveys on selected household residents in 12 streets of Yangpu District. The survey questions included their understanding of COPD name， lung function test， and COPD related knowledge. Multivariate logistic regression analysis was used to analyze the influencing factors of awareness rate. ResultsA total of 1 440 people were ultimately included in the analysis， and the awareness rates of COPD name， lung function test， and COPD awareness were 19.93%， 18.61%， and 14.95%， respectively. Among the people who knew the name of COPD， awareness rate of shortness of breath or dyspnea was the highest （84.12%） in the three main symptoms of COPD. Among the main risk factors of COPD， second-hand smoke（86.78%）and smoking （85.82%） were the highest. The main ways to obtain knowledge of COPD names were through television （12.60%） and the internet （11.97%）. The results of multivariate logistic regression analysis showed that men were significantly higher than women in the awareness of COPD name， lung function test， and COPD knowledge， with the OR values of （OR=1.39， 95%CI：1.08‒1.79）， （OR=1.47，95%CI：1.12‒1.92） and （OR=1.37，95%CI：1.02‒1.84）， respectively. The awareness rate of COPD names and lung function tests was the highest among people aged ≥ 65 years old， while the awareness rate of COPD knowledge was the highest among people aged 35‒50 years old. The awareness rate of COPD names was the highest among people with college education or above， civil servants， teachers， and medical staff， people with an annual household income of 100 000‒200 000 yuan. ConclusionThe overall awareness rate of COPD names， lung function tests， and COPD related knowledge among residents in Yangpu District is still at a low level. We should intensify the promotion and education of COPD among key groups such as women， young people， and those with low income， in order to improve the overall awareness rate of COPD among the population.