To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

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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

OBJECTIVES: This study aimed to explore the potential target and molecular mechanism of Eclipta prostrata L-Ligustrum Lucidum Ait (EPL-LLA) in the treatment of periodontitis by using network pharmacology and molecular docking technology, and to explore its biocompatibility, regulatory effects on inflammatory factors, and antioxidant acti-vity through in vitro experiments. METHODS: The active components and potential targets of EPL-LLA were screened and predicted through a variety of databases, and the intersection of EPL-LLA and periodontitis targets was selected. The protein interaction network (PPI) was analyzed by the string platform. The Metascape database was used for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The active ingredients from the top 6 degrees were docked with the core targets, and the results of binding energy were visualized. An in vitro cell model was established to evaluate the biocompatibility, modulation of inflammatory factors, and antioxidative effects of EPL-LLA through cell counting kit-8 (CCK-8), quantitative real-time polymerase chain reaction (qRT-PCR) and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe assays. RESULTS: Screening revealed 13 active components in EPL corresponding to 220 potential targets, 10 active components in LLA corresponding to 283 potential targets, and 1 643 periodontitis-related targets, with 91 shared targets among the three. GO analysis of the shared targets yielded 5 271 entries, while KEGG enrichment analysis indicated involvement in 253 signaling pathways. Molecular docking confirmed stable binding between the top 6 active components and core targets. CCK-8 assays demonstrated good biocompatibility of EPL-LLA at concentrations 0.02 mg/mL (P<0.05). qRT-PCR showed that EPL-LLA reduced the mRNA expression of pro-inflammatory factors in macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide while upregulating anti-inflammatory factor mRNA expression (P<0.05). DCFH-DA fluorescence probe assays confirmed the reactive oxygen species (ROS)-scavenging capacity of EPL-LLA (P<0.05). CONCLUSIONS EPL-LLA may treat periodontitis through multi-component, multi-target, and multi-pathway mechanisms, providing a theoretical basis for further research on its therapeutic potential.
Periodontitis/drug therapy* ; Molecular Docking Simulation ; Eclipta/chemistry* ; Humans ; Protein Interaction Maps ; Ligustrum/chemistry* ; Antioxidants/pharmacology* ; Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

The European Society of Endodontology published the S3-level clinical practice guideline for the treatment of pulpal and apical disease in October 2023, which provides best current therapeutic strategies supported by scientific evidences. The guideline was divided into four parts: the diagnosis and treatment of pulpitis, diagnosis and nonsurgical treatment of apical periodontitis, surgical treatment of apical periodontitis, and regenerative treatment. This article aims to introduce and interpret the guideline, and to better manage patients with pulpitis and apical periodontitis for preserving teeth over a patient′s lifetime in China.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Video-based intelligent action recognition remains challenging in the field of computer vision.The review analyzes the state-of-the-art methods of video-based intelligent action recognition,including machine learning methods with handcrafted features,deep learning methods with automatically extracted features,and multi-information fusion methods.In addition,the important medical applications and limitations of these technologies in the past decade are introduced,and the interdisciplinary views on the future application to improve human health are also shared.

Objective:To investigate the perinatal prognosis and its impact factors for premature infants with twin-twin transfusion syndrome (TTTS) who were born at ≤34 weeks of gestation.Methods:A retrospective study was conducted on 68 pregnancies of TTTS with gestational age ≤34 weeks at delivery, among them 106 preterm infants (TTTS group) were admitted to the neonatal intensive care unit of the First Affiliated Hospital, Sun Yat-sen University from January 2003 to February 2019. During the same period, another 178 twins without TTTS, congenital malformation, and intrauterine intervention who matched the TTTS group in maternal age (differences within two years) and gestational age (differences within one week) were assigned as non-TTTS group. Perinatal prognosis of TTTS infants born at ≤34 weeks was analyzed by comparing the differences in postnatal early complications and perinatal outcomes (survival time morn than 28 days or not) between the TTTS and non-TTTS groups, recipient and donor twins, mild and severe TTTS infants, and among TTTS infants with different intrauterine interventions. The risk factors for perinatal survival in TTTS infants with gestational age ≤34 weeks were analyzed. Two independent samples t-test, one-way analysis of variance, rank-sum test, Chi-square test, and ordered logistic regression were used for statistical analysis. Results:(1) Among the 68 pregnancies, the overall perinatal survival rate of the neonates was 72.1% (98/136), the double-twin survival rate was 48.5% (33/68), and the rate of at least one survivor was 95.6% (65/68). (2) In the TTTS group, 62 were recipients and 44 were donors. Stage Ⅰ-Ⅱ TTTS was found in 41 cases (mild TTTS group) and stage Ⅲ-Ⅴ in 65 cases (severe TTTS group). (3) The rate of severe brain injury was higher in the severe-TTTS group than those in the mild-TTTS group [9.2% (6/65) vs. 0.0% (0/41), χ 2=4.01, P=0.045]. (4) Gestational age ≤28 weeks ( OR=101.90, 95% CI: 5.07-2 048.37), stage Ⅳ ( OR=14.04, 95% CI: 1.56-126.32) and stage Ⅴ TTTS ( OR=51.09, 95% CI: 3.58-728.81) were independent risk factors for death within 28 days (all P<0.05). (5) Compared with the non-TTTS group, the TTTS group had higher rates of neonatal anemia [51.9% (55/106) vs. 33.1% (59/178), χ 2=9.71], polycythemia [5.7% (6/106) vs. 0.6% (1/178), χ 2=7.18], neonatal persistent pulmonary hypertension [3.8% (4/106) vs. 0.0% (0/178), χ 2=6.81], sepsis [15.1% (16/106) vs. 7.3% (13/178), χ 2=4.40], state Ⅲ or higher retinopathy of prematurity [3.8% (4/106) vs. 0.0% (0/178), χ 2=6.81], congenital cardiac structural abnormality [19.8% (21/106) vs. 0.6% (1/178), χ 2=33.45], heart failure [8.5% (9/106) vs. 0.6% (1/178), χ 2=12.29], and renal insufficiency [14.2% (15/106) vs. 1.1% (2/178), χ 2=20.04] (all P<0.05). Conclusions:Compared with the twin premature infants without TTTS, those with TTTS and ≤34 gestational age were more likely to have cardiac, cerebral, and renal complications. The more severe the TTTS, the higher the incidence of severe brain injury. TTTS preterm infants with gestational age ≤28 weeks and stage Ⅳ or above have high risk of death.

Patients with chronic obstructive pulmonary disease have the disease phenomenon of fear of exercise because of dyspnea, which can accelerate the body degradation rate, weaken muscle strength, reverse increase dyspnea, and delay the recovery of the disease. As a result, this article examines the theoretical underpinnings and specific measures of dyspnea belief intervention programs for chronic obstructive pulmonary disease patients at home and abroad, summarizes the limitations of previous studies, and makes pertinent recommendations in an effort to serve as a guide for early patient prevention and the development of scientific and feasible intervention programs.