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

Objective To compare TyG index between the patients with CHF and ADHF to eluci-date the metabolic difference between these two stages.Methods A total of 1156 HF patients ad-mitted in Taizhou People's Hospital between January 2020 and December 2022 were enrolled,and according to 2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Fail-ure,they were divided into CHF group(365 cases)and ADHF group(791 cases).The clinical da-ta,results of laboratory tests,and cardiovascular history were collected,and TyG index was calcu-lated.All-cause death outcome was observed in ADHF patients during a follow-up of 1 year.Results The TyG index was significantly lower in the ADHF group than the CHF group[8.27(7.99,8.62)vs 8.35(8.04,8.75),P=0.001].In the ADHF group,the TyG index was positively correlated with SBP,DBP,TC,TG,LDL-C,FPG,HbA1c,BMI,and LVEF,and negatively with age(P＜0.01).In the CHF group,the index was positively correlated with DBP,TC,TG,LDL-C,FPG,BMI,and HbA1c,and negatively with age(P＜0.05,P＜0.01).Both univariate and multiva-riate logistic regression analyses indicated that the TyG index was a protective factor for ADHF(OR=0.647,95％CI:0.503～0.832,P=0.001;OR=0.694,95％CI:0.536～0.898,P=0.005).Multivariate logistic regression analysis showed that the index in ADHF patients was a protective factor for one-year all-cause mortality(OR=0.483,95％CI:0.254-0.916;P=0.026).Conclusion TyG index might be regarded as an important marker for assessing the metabolic status in HF patients and predicting the prognosis in ADHF patients.

Objective:To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL).Methods:A child who was admitted to Ningbo Women and Children′s Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063).Results:Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, pathogenic copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. Conclusion:For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.

Objective:To investigate the clinical characteristics and independent predictors of progression-free survival (PFS)in patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma in the real world.Methods:This was a retrospective observational study.The clinical data of 74 EGFR mutation-positive lung adenocarcinoma patients who visited the Geriatric Oncology Department of the Fisrt Affiliated Hospital of Nanjing Medical University from January 2020 to March 2025 were retrospectively collected.Retrospective analysis was performed on baseline clinical characteristics(gender, age, smoking history, stage, etc.), EGFR mutation types, and treatment follow-up data(PFS, treatment regimens). Descriptive statistics were used to summarize the baseline clinical characteristics of the patients.The distribution differences in clinical characteristics between the elderly group and the non-elderly group were compared.Kaplan-Meier survival curves were plotted with Log-rank test, and the Cox proportional hazards model was used to screen for independent prognostic factors.Results:The incidence of comorbidities in the elderly group(48.78%, 20/41)was significantly higher than that in the non-elderly group(24.24%, 8/33), with a statistically significant difference( χ2=4.681, P=0.031). No statistically significant differences were observed between groups in other variables[gender, stage, presence of multiple metastases, smoking history, Eastern cooperative oncology group (ECOG)score, treatment regimens, mutation types](all P>0.05). The median PFS (mPFS)in the elderly group was significantly shorter than that in the non-elderly group(18.20 months vs.26.78 months, Log-rank χ2=3.930, P=0.047). No significant differences in mPFS were found among gender, stage, presence of multiple metastases, smoking history, comorbidity status, ECOG score, treatment regimens, EGFR mutation types or types of tyrosine kinase inhibitor(TKI)(all P>0.05). Multivariate Cox regression further confirmed that advanced age(≥65 years)is an independent predictor of shortened PFS( HR=2.67, 95% CI: 1.04~6.85, P=0.041). The overall incidence of TKI treatment-related adverse reactions was 40.58%(28/69), with a grade ≥3 adverse event rate of 11.59%(8/69). Common adverse reactions included rash, oral mucositis, and diarrhea.The incidence of TKI-related adverse reactions in the elderly group(17/39, 43.59%)was higher than that in the non-elderly group(11/30, 36.67%), but the difference was not statistically significant( χ2=1.038, P=0.196). Conclusions:Age is an independent predictor of PFS in patients with EGFR-mutant lung adenocarcinoma, and its effect is not interfered with by comorbidities or mutation subtypes.

Objective:To screen the optimal machine learning model for predicting the recurrence condition of hepatocellular carcinoma (HCC) at different time points post-surgery, based on the cutoff value of the Ki67 positive proliferation index condition calculated from recurrence-free survival and combined with various clinical features.Methods:retrospective study included initially treated patients with solitary HCC who underwent radical surgery at the Fifth Medical Center of the PLA General Hospital from January 2013 to March 2023. Data included general clinical data, preoperative laboratory parameters, and surgical pathology information about the subjects. The postoperative recurrence status was assessed by querying the medical record system or by telephone follow-up. The Ki67 positive index cutoff value was determined by the X-tile software based on the patient's recurrence-free survival status and time analysis. Survival rates were calculated using the Kaplan-Meier method, and survival curves were plotted. The study population was randomly divided into training and testing groups in a 7:3 ratio using a computer-generated random number method. The minimum redundancy maximum relevance (mRMR) method was used for feature variable selection. Predictive models for postoperative HCC recurrence conditions in patients with HCC were constructed using random forest, support vector machine, logistic regression, and gradient boosting decision tree machine learning algorithms. Inter-group comparisons for continuous data were performed using the t-test or Mann-Whitney U test. Inter-group comparisons of enumeration data were performed using the Pearson χ2 test, continuity-corrected χ2 test, or Fisher's exact test. Results:The cutoff values for the Ki67 positivity index were 0.3 and 0.5 in 510 cases, with a follow-up time ranging from 1.2 to 11.4 years (median: 6.2 years). The recurrence-free survival time was between 1 and 135 months (median: 32 months), with recurrence-free survival rates post-surgery at 1, 2, 3, and 5 years were 87.5%, 77.1%, 61.2%, and 54.5%, respectively. The top five variables predicted HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years, in accordance with information obtained by the mRMR screen out. The Ki67 positivity index screened a successfully constructed machine learning model to predict HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years. The machine learning model based on the gradient boosting decision tree algorithm had the best prediction performance among them (areas under the receiver operating characteristic curves for predicting HCC recurrence within six months in the training and validation sets were 0.996 and 0.946, and accuracies were 0.972 and 0.935, respectively).Conclusion:A machine learning model was successfully constructed using the Ki67 positivity index combined with four readily available clinical features to predict HCC recurrence. The machine learning model based on the gradient boosting decision tree algorithm demonstrated the best performance in terms of predicting HCC recurrence within six months after surgery.

OBJECTIVE: To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL). METHODS: A child who was admitted to Ningbo Women and Children's Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063). RESULTS: Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. CONCLUSION For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.
Child, Preschool ; Humans ; DNA Copy Number Variations/genetics* ; Down Syndrome/genetics* ; GATA1 Transcription Factor/genetics* ; Leukemia/congenital* ; Mosaicism ; Mutation ; Retrospective Studies ; Whole Genome Sequencing

Objective:To explore latent class of symptoms related to psychological trauma and characteristics in patients with pregnancy loss, and to analyze the related influencing factors.Methods:From July 2022 to June 2024, a convenience sampling method was used to select 709 cases of pregnancy loss patients who visited the Maternity Department of the First Affiliated Hospital of Zhengzhou University as the survey subjects. The survey was conducted using the general information questionnaire, the post-traumatic stress disorder (PTSD) self-assessment scale, the hospital anxiety and depression scale, and the pittsburgh sleep index scale. Exploratory latent class analysis (LCA) of symptoms related to psychological trauma was performed by Mplus8.3, and then multivariate logistic regression was used to identify the factors influencing the latent classes.Results:A total of 691 patients with pregnancy loss were eventually investigated, with a total PTSD score of 24.00 (19.00, 33.00), a total anxiety score of 6.00 (3.00, 9.00), a total depression score of 6.00 (3.00, 9.00), and a total sleep disorder score of 7.00 (4.00, 9.00). Symptoms related to psychological trauma could be classified into 3 potential categories named high symptom group [20.4% (141/691)], anxiety-depression group [15.3% (106/691)] and low symptom group [64.3% (444/691)]. The result of multivariate logistic regression analysis showed that per capita monthly household income >8 000 yuan ( OR=0.477, 95% CI: 0.272-0.835, P=0.010) and having a spouse accompanying the patient at the time of admission ( OR=0.352, 95% CI: 0.234-0.532, P<0.001) were protective factors for the high symptom group, and gestational week≥28 weeks ( OR=3.192, 95% CI: 1.619-6.292, P=0.001) and assisted reproductive pregnancy ( OR=1.877, 95% CI: 1.075-3.277, P=0.027) were risk factors for the high symptom group. Conclusion:Symptoms associated with psychological trauma in patients with pregnancy loss have distinct categorical characteristics, and healthcare professionals should focus on patients with pregnancy loss in the high symptom group during hospitalization, and adopt targeted interventions according to the symptoms related to psychological trauma in different categories of patients with pregnancy loss in order to avoid serious psychological problems.

Stress urinary incontinence is one of the common symptoms of women during pregnancy and postpartum, which has a lasting impact on the life of patients, and is also one of the public health issues of concern in the world. In this study, the generation, development, construction process, prediction performance and management application of stress urinary incontinence risk prediction models during pregnancy and postpartum were reviewed, with a view to improving the understanding of health care workers on stress urinary incontinence risk prediction models during pregnancy and postpartum, and providing references for promoting the health management of female patients.

Objective:To explore latent class of symptoms related to psychological trauma and characteristics in patients with pregnancy loss, and to analyze the related influencing factors.Methods:From July 2022 to June 2024, a convenience sampling method was used to select 709 cases of pregnancy loss patients who visited the Maternity Department of the First Affiliated Hospital of Zhengzhou University as the survey subjects. The survey was conducted using the general information questionnaire, the post-traumatic stress disorder (PTSD) self-assessment scale, the hospital anxiety and depression scale, and the pittsburgh sleep index scale. Exploratory latent class analysis (LCA) of symptoms related to psychological trauma was performed by Mplus8.3, and then multivariate logistic regression was used to identify the factors influencing the latent classes.Results:A total of 691 patients with pregnancy loss were eventually investigated, with a total PTSD score of 24.00 (19.00, 33.00), a total anxiety score of 6.00 (3.00, 9.00), a total depression score of 6.00 (3.00, 9.00), and a total sleep disorder score of 7.00 (4.00, 9.00). Symptoms related to psychological trauma could be classified into 3 potential categories named high symptom group [20.4% (141/691)], anxiety-depression group [15.3% (106/691)] and low symptom group [64.3% (444/691)]. The result of multivariate logistic regression analysis showed that per capita monthly household income >8 000 yuan ( OR=0.477, 95% CI: 0.272-0.835, P=0.010) and having a spouse accompanying the patient at the time of admission ( OR=0.352, 95% CI: 0.234-0.532, P<0.001) were protective factors for the high symptom group, and gestational week≥28 weeks ( OR=3.192, 95% CI: 1.619-6.292, P=0.001) and assisted reproductive pregnancy ( OR=1.877, 95% CI: 1.075-3.277, P=0.027) were risk factors for the high symptom group. Conclusion:Symptoms associated with psychological trauma in patients with pregnancy loss have distinct categorical characteristics, and healthcare professionals should focus on patients with pregnancy loss in the high symptom group during hospitalization, and adopt targeted interventions according to the symptoms related to psychological trauma in different categories of patients with pregnancy loss in order to avoid serious psychological problems.

Objective To compare TyG index between the patients with CHF and ADHF to eluci-date the metabolic difference between these two stages.Methods A total of 1156 HF patients ad-mitted in Taizhou People's Hospital between January 2020 and December 2022 were enrolled,and according to 2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Fail-ure,they were divided into CHF group(365 cases)and ADHF group(791 cases).The clinical da-ta,results of laboratory tests,and cardiovascular history were collected,and TyG index was calcu-lated.All-cause death outcome was observed in ADHF patients during a follow-up of 1 year.Results The TyG index was significantly lower in the ADHF group than the CHF group[8.27(7.99,8.62)vs 8.35(8.04,8.75),P=0.001].In the ADHF group,the TyG index was positively correlated with SBP,DBP,TC,TG,LDL-C,FPG,HbA1c,BMI,and LVEF,and negatively with age(P＜0.01).In the CHF group,the index was positively correlated with DBP,TC,TG,LDL-C,FPG,BMI,and HbA1c,and negatively with age(P＜0.05,P＜0.01).Both univariate and multiva-riate logistic regression analyses indicated that the TyG index was a protective factor for ADHF(OR=0.647,95％CI:0.503～0.832,P=0.001;OR=0.694,95％CI:0.536～0.898,P=0.005).Multivariate logistic regression analysis showed that the index in ADHF patients was a protective factor for one-year all-cause mortality(OR=0.483,95％CI:0.254-0.916;P=0.026).Conclusion TyG index might be regarded as an important marker for assessing the metabolic status in HF patients and predicting the prognosis in ADHF patients.