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

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Background The residues of pharmaceutical and personal care products (PPCPs) in aquatic environments have become an increasingly prominent urban pollution issue, attracting widespread attention. The analysis of PPCPs pollution in water environments holds profound implications in Zhengzhou, a strategically important city in central China. Objective To analyze the pollution characteristics of PPCPs, such as antidepressants and antibiotics, in rivers of Zhengzhou and assess associated ecological risk. Methods Water samples were collected from three rivers of Zhengzhou, and 13 PPCPs (5 antibiotics and 8 antidepressants) were analyzed quantitatively by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS/MS) after automatic solid phase extraction. Risk quotient (RQ) was applied to assess ecological risk of PPCPs with high concentration. Results The primary antibiotics pollutants were norfloxacin and ofloxacin, both with a detection rate of 100%. Among antidepressants, venlafaxine and citalopram showed the highest detection rates at 92.3% and 88.5%, respectively. The detected antibiotics with the highest average concentrations included ofloxacin and sulfamethoxazole with concentrations of 99.8 ng·L⁻¹and 96.2 ng·L⁻¹, respectively, while antidepressants venlafaxine and citalopram were detected with the highest average concentrations of 15.2 ng·L⁻¹and 1.35 ng·L⁻¹, respectively. The inter-river comparisons revealed statistically significant differences in contaminant loads (P<0.05). The sums of average PPCP concentrations at sampling points in the Jialu River and Suoxu River were 83.4 ng·L⁻¹ and 100.4 ng·L⁻¹, respectively. The Xiaoqing River exhibited higher pollution levels than both the Jialu and Suoxu Rivers, with a total average concentration of 478.4 ng·L⁻¹, where ofloxacin and sulfamethoxazole were identified as the predominant pollutants. The results of ecological risk assessment indicated the RQ contributed by sulfamethoxazole ranged between 0.50−0.95 in the Xiaoqing River, suggesting a controllable risk but requiring prioritized mitigation strategies. The RQ values of norfloxacin were distributed within the range of 0.10-0.30, indicating a moderate ecological risk. The RQ values for ofloxacin and venlafaxine remained below 0.10, indicating a lower risk level. Conclusion PPCPs contamination is positive in the rivers of Zhengzhou, and sulfamethoxazole and ofloxacin are the primary cantaminants. The Xiaoqing River exhibits the highest pollution levels. The initial risk assessment show that sulfamethoxazole and norfloxacin pose potential ecological risks, requiring prioritized contamination management.

Objective:To improve the risk management process for clinical trial projects using healthcare failure mode and effect analysis(HFMEA), for references for enhancing the risk identification and preventing capabilities of drug clinical trial institutions.Methods:From June to December 2022, this study focused on the project management process of a clinical trial centre in a tertiary public hospital. Following HFMEA procedures, a research team was established. Core processes prone to failure modes in the drug clinical trial project management and their potential failure modes were identified through group discussions, literature analysis, the Delphi method, and decision tree analysis. High-risk failure modes were screened via risk assessment, corresponding improvement measures were formulated and performed, and their effectiveness was validated.Results:The study identified 6 main processes, 17 sub-processes, and 102 potential failure modes. Delphi analysis confirmed 88 failure modes, with 19 having a failure risk priority number(RPN)≥8.00. Decision tree analysis identified 16 high-risk failure modes, involving 5 main processes and 10 sub-processes. Targeted improvements, such as adopting standardized hospital contract templates and setting deadlines for final payment settlement, etc., were implemented. One year post-implementation(January 2024), the RPN for all 16 high-risk failure modes were<8.00.Conclusions:HFMEA could help hospital clinical trial institutions comprehensively and systematically identify high-risk failure modes in the project management process, develop targeted improvement measures, and improve the level of drug clinical trial project management.

Objective To gain an in-depth understanding of influencing factors on the preventive behaviors of operating room nurses regarding hypothermia during cesarean sections,and to provide references for promoting the prevention of hypothermia during cesarean sections.Methods A descriptive qualitative research approach was adopted,based on the theoretical framework of the Precede-Proceed Model to develop an interview outline.Semi-structured interviews were conducted with 12 operating room nurses,and the interview data were analyzed using directed content analysis.Results The influencing factors were categorized into 3 main themes and 8 sub-themes.①Predisposing factors:insufficient theoretical knowledge,low risk awareness among healthcare providers.②Enabling factors:rational allocation of equipment/resources,proficient operational skills,targeted and effective training programs,and standardized preventive procedures.③Reinforcing factors:the need to enhance team cooperation,the need to improve the regulatory mechanism.Conclusion Nursing managers should strengthen education and training to enhance nurses'awareness and skill levels in preventing hypothermia,improve equipment resources and build an information-based assessment and decision support system to promote the implementation of hypothermia prevention behaviors.Additionally,facilitating team collaboration and utilizing information construction to collect and analyze quality indicators can strengthen quality management and promote continuous improvement in the quality of hypothermia prevention during cesarean sections.

Objective To observe prenatal ultrasonic findings of fetal malformation of cortical development(MCD).Methods Totally 37 singleton fetuses with MCD diagnosed by fetal cranial MRI and/or genetic examination were retrospectively enrolled,and prenatal ultrasonic manifestations were observed.Results Among 37 fetuses,29(29/37,78.38％)were found with abnormal Sylvian fissure,26(26/37,70.27％)with widened/asymmetrical lateral ventricles,22(22/37,59.46％)with abnormal surface sulci,14(14/37,37.84％)with abnormal cavity of septum pellucidum(CSP)/corpus callosum(CC),11(11/37,29.73％)with midline deviation/curvature,11(11/37,29.73％)with widened subarachnoid space,10(10/37,27.03％)with head circumference＜2 standard deviation below mean value,9(9/37,24.32％)with abnormalities in the cerebellar hemisphere/vermis,7(7/37,18.92％)with abnormal echoes in the brain parenchyma,7(7/37,18.92％)with midline cysts and 2(2/37,5.41％)with enlarged ganglion eminence.Conclusion Fetal MCD mainly presented as abnormal Sylvian fissure,widened/asymmetrical lateral ventricles and abnormal surface sulci,which might accompanied by abnormal CSP/CC,midline deviation/curvature,widened subarachnoid space and abnormal head circumference in prenatal ultrasound.

Objective To explore the materials and embolization technique employed in precision superselective transarterial embolization for the treatment of acute renal hemorrhage.Methods The data of 50 patients with acute renal hemorrhage who underwent precision superselective transarterial embolization were retrospectively analyzed.The angiographic findings,embolic materials and embolization methods were collected.The main outcome measures were technical success rate,clinical efficacy and renal function.Results In this study,44 patients had positive angiographic findings.The clinical success rate was 90.9%(40/44)after first precision superselective transarterial embolization.In patients of failure of first embolization,3 patients underwent successful repeated embolization and 1 patient refused repeat embolization.Empirical embolization was carried out among the 6 patients with negative angiographic findings.In 32 patients with complete data for estimated glomerular filtration rate(eGFR),there was no statistical difference before and those measured 7 d after precision superselective transarterial embolization.Conclusion Precision superselective transarterial embolization technique is an effective method for the treatment of acute renal hemorrhage,preserving renal function.

BACKGROUND:Neuroinflammation is a major cause of exacerbation after spinal cord injury.In recent years,pyroptosis has received much attention due to its remarkable pro-inflammatory features.Some of these natural products can significantly inhibit the inflammatory response and improve the damaged nerve function by regulating the level of pyroptosis after spinal cord injury,which provides a new therapeutic idea for spinal cord injury.OBJECTIVE:To summarize the mechanism of action of natural products in regulating pyroptosis for the treatment of spinal cord injury,with a view to providing lessons and references for future research on the treatment of spinal cord injury.METHODS:The search terms"spinal cord injury,pyroptosis,inflammasome,natural products,natural compounds,traditional Chinese medicine"in Chinese and English were used to search for relevant literature since the establishment of the database up to September 2024 in the databases of PubMed,Web of Science,WanFang,and CNKI.According to the inclusion and exclusion criteria,75 relevant articles were finally obtained.RESULTS AND CONCLUSION:(1)Pyroptosis is an important pro-inflammatory pathway in spinal cord injury,and controlling pyroptosis is an effective way to improve damaged nerve function.(2)Some natural products can regulate pyroptosis via the NLRP3/Caspase-1 classical pyroptosis pathway,the NF-κB-related pathway,other upstream pathways such as Nrf2/HO-1,and autophagy,thereby affecting the level of tissue inflammation and accelerating neurological recovery after spinal cord injury.(3)The anti-pyroptosis effects of these natural products are mostly dependent on the NLRP3 classical pyroptosis pathway,and there is a lack of studies on other pyroptosis pathways.(4)There are still many problems in this field,such as the fact that these natural products are not currently supported by evidence from appropriate clinical studies.(5)The natural product has great potential in regulating pyroptosis and is expected to be a powerful weapon in the treatment of spinal cord injury.

Objective:To investigate the predictive role of intrapartum ultrasound indicators on the difficulty of vacuum-assisted delivery.Methods:A prospective cohort study was conducted. The study subjects were singleton pregnant women hospitalized for delivery at the Third Affiliated Hospital of Sun Yat-sen University from February 2021 to December 2022, who had indications for vacuum-assisted delivery, and completed intrapartum ultrasound examination within 10 minutes before the procedure. Intrapartum ultrasound indicators included fetal position, angle of progression (AOP), and head-perineum distance (HPD). Based on the difficulty of vacuum-assisted delivery, the subjects were divided into easy and difficult groups. The fetal position, AOP, and HPD before vacuum-assisted delivery and delivery outcomes were compared between the two groups to explore the correlation and predictive value of intrapartum ultrasound indicators on the difficulty of vacuum-assisted delivery. Statistical and predictive value analyses were performed using independent-sample t-test, U-test, Chi-square (or Fisher's exact) test, logistic regression analysis, and receiver operating characteristic (ROC) curve. Results:A total of 162 cases were included in the study, with 120 in the easy and 42 in the difficult groups. The age of the 162 pregnant women ranged from 20 to 44 years, with an average of (30.6±3.9) years; 107 cases (66.0%) were first pregnancies, and 139 cases (85.8%) were primipara. (1) The fetal head stations in the difficult and easy groups were 2.3 (2.0-2.5) cm and 2.0 (2.0-2.5) cm, respectively, with no statistically significant difference ( P>0.05). The AOP during the interval and contraction periods and the ΔAOP in the difficult group were smaller than those in the easy group [ (138.1±8.8) vs. (143.8±7.9), t=3.89; (148.7±9.3) vs. (157.9±8.9), t=5.67; and (10.6±6.4) vs. (14.1±6.3), t=3.08; all P<0.01], while the HPD during the interval and contraction periods and ΔHPD in the difficult group were greater than those in the easy group [(3.4±0.5) cm vs. (3.2±0.4) cm, t=－2.69; (2.8±0.5) cm vs. (2.4±0.5) cm, t=－4.70; (－0.5±0.4) cm vs. (－0.8±0.5) cm, t=－2.83; all P<0.01]. (2) In the difficult group, seven cases required forceps delivery after 2-3 vacuum cup detachments; in the easy group, all cases were successfully delivered after 1-2 vacuum tractions. The duration of vacuum extraction was longer in the difficult group [7.0 (6.0-10.0) min vs. 3.0 (2.0-3.0) min, Z=9.65] (all P<0.001). (3) In the difficult group, four cases had severe maternal and neonatal delivery complications, including two cases of shoulder dystocia, one case of vesicovaginal fistula after failed vacuum extraction converted to forceps delivery, and one case of third-degree perineal tear after failed vacuum extraction converted to forceps delivery. In the easy group, one case had shoulder dystocia with mild neonatal asphyxia. The rate of vaginal tears in the difficult group was higher than in the easy group [47.6% (20/42) vs. 29.2% (35/120)] ( χ2=4.72, P=0.030). The incidence of postpartum hemorrhage in the difficult and easy groups was 11.9% (5/42) and 8.3% (10/120), respectively, with no statistically significant difference (Fisher's exact test, P=0.539). No cases required cesarean section after failed vacuum extraction. The incidence of scalp hematoma was higher in the difficult group than in the easy group [28.6% (12/42) vs. 11.7% (14/120), χ2=6.60, P=0.010]. The two groups had no statistically significant differences in the incidence of other neonatal complications. (4) Multivariate logistic regression analysis identified three independent variables associated with difficult vacuum extraction: maternal age, AOP and HPD during contraction. The ROC curve was used to test the predictive value of the multivariate model for difficult vacuum extraction, with an area under the curve of 0.808 (95% CI: 0.734-0.882) ( P<0.001). When the maximum Youden index (0.487) was taken, the sensitivity and specificity of the model in predicting difficult vacuum extraction were 0.762 (95% CI: 0.696-0.828) and 0.725 (95% CI: 0.656-0.794), respectively. Conclusions:AOP and HPD are related to the difficulty of vacuum extraction. The risk of difficult vacuum extraction increases with advanced maternal age, smaller AOP and larger HPD during the contraction phase.