Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Objective To investigate the ameliorative effect of ginsenoside Rf on endometriosis(EMS)and its mechanism.Methods In animal experiments,Wistar female rats were randomly divided into sham group(laparotomy without other treatment),model group(EMS construction),low dose group(1.0 mg·kg-1 ginsenoside Rf),middle dose group(2.0 mg·kg-1 ginsenoside Rf),high dose group(3.0 mg·kg-1 ginsenoside Rf),positive group(0.25 mg·kg-1 pregnrienone capsule).The volume of ectopic lesions and the number of painful twisting were detected;the apoptosis rate in tissues was detected by TdT mediated dUDP nick end labeling(Tunel)assay;the expression of related proteins in each group was detected by Western blot assay.Cell experiment:The isolated primary rat endometrial cells were randomly divided into control group(normal tissue isolation),EMS group(EMS cells),Rf group(20 μmol·L-1 ginsenoside Rf treated EMS cells),combined group(20 μmol·L-1 ginsenoside Rf and 50 μmol·L-1 autophagy inhibitor 3-MA treated EMS cells).Western blot assay was used to detect the expression of related proteins;flow cytometry was used to detect apoptosis.Results Animal experiment:The times of body twisting in sham group,model group,high dose group and positive group were 0,37.10±4.64,14.70±1.90 and 20.20±1.78,respectively;the ectopic lesion volumes were 0,(118.91±19.51),(50.11±9.69)and(37.64±3.56)mm,respectively;the apoptosis rates were(3.43±0.33)％,(3.22±0.27)％,(20.42±1.82)％and(22.92±2.67)％,respectively;Beclin 1 protein expression were 0.32±0.03,0.36±0.04,0.79±0.12,0.35±0.07,respectively;glutathione peroxidase 4(GPX4)protein expression were 1.10±0.07,0.94±0.11,0.53±0.03,0.96±0.16,respectively.The above indexes of the model group were compared with those of the sham group,and the above indexes of the high dose group were compared with those of the model group,and the differences were significant(all P＜0.05).Cell experiment:Beclin1 protein expression in control group,EMS group,Rf group and combined group were 0.22±0.05,0.31±0.03,0.52±0.07 and 0.19±0.03,respectively;GPX4 protein expression were 0.97±0.07,0.81±0.09,0.63±0.05 and 1.05±0.09,respectively;the apoptosis rates were(3.48±0.04)％,(3.42±0.23)％,(21.66±2.95)％and(12.51±1.15)％,respectively;the above indexes in Rf group were compared with those in EMS group,and the above indexes in combined group were compared with those in Rf group,and the differences were significant(all P＜0.05).Conclusion Ginsenoside Rf can improve endometrial lesion,pain sensitivity and apoptosis in EMS rats,which may be related to the regulation of autophagy dependent ferroptosis.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fine motor control difficulties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was significantly downregulated in the medial prefrontal cortex of young mice after multiple sevoflurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fine motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.
Animals ; Sevoflurane/toxicity* ; Microglia/drug effects* ; Anesthetics, Inhalation/adverse effects* ; Mice ; Mice, Inbred C57BL ; Receptors, Erythropoietin/metabolism* ; Neuronal Plasticity/drug effects* ; Male ; Prefrontal Cortex/drug effects* ; Erythropoietin/pharmacology* ; Signal Transduction/drug effects*

Humans ; Supranuclear Palsy, Progressive ; Acupuncture Therapy

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

In view of the limitations of the high operational difficulty, safety hazards and adverse reactions of traditional fire needle, and unclear treatment parameters of existing electric fire needles, a new digital electric fire needle instrument was designed and developed in this study. This instrument is a gun type structure, consisting of a gun body, a power supply interface on the gun body, a display unit and a drive unit, a heating unit, a cooling unit, a positioning unit, and a needle inserting unit in the gun body. This instrument can digitally realize the regulation of parameters such as fire needle inserting temperature, depth and speed, and it has the advantageous features of intelligent needle burning, precise positioning, and safe and easy operation. This instrument meets the needs of more patients, medical professionals and scientific researchers, and is conducive to promoting the development of fire needle acupuncture therapy.
Humans ; Needles ; Heating ; Research Personnel ; Temperature

Aim To establish the 3D hepatocyte model by selecting the humanized hepatocyte HepG2 cells and 3D cell culture methods, and to establish the 3D hepatocyte cytokinesis-block micronucleus cytome(CBMN-cyt)assay and 3D hepatocyte comet assay by using chemicals of different mode of action.Methods In this study, a scaffold-free culture method was used to successfully establish a 3D HepG2 hepatocyte spheroid model.The appearance of the sphere, the survival rate of cells inside the sphere, the gene expression of phase I and II metabolic enzymes, and the expression of liver-specific biomarkers were selected as the observation indicators to obtain the best culture conditions for the 3D hepatocyte model.The 3D hepatocyte model was combined with in vitro micronucleomics test and in vitro comet test to explore its applicability for genotoxicity test.Results The best culture conditions for the 3D hepatocyte model was 5×103 cells/20 μL /drop inoculation, cultivating for seven days.A 3D hepatocyte CBMN-cyt assay was established using mitomycin C(MMC), a micronucleus positive compound, and the results showed that it could successfully detect the genotoxicity and cytotoxicity of MMC.Compared with the CBMN-cyt results of 2D hepatocyte model, 3D hepatocyte model had higher sensitivity in detecting MN and Nbud.The 3D hepatocyte comet assay methods were established using the known in vivo and in vitro comet assay positive compound methyl methanesulfonate(MMS), and the results showed that MMS could significantly increase the tail DNA% of 3D hepatocytes with low cytotoxicity.The sensitivity of 3D hepatocyte model to MMS genotoxicity detection was higher than that of 2D cells.Conclusions The 3D hepatocyte model established in this study is easy to use and low in cost, and shows good sensitivity and specificity in the in vitro micronucleus test and comet test, suggesting that the 3D hepatocyte genotoxicity test method is used in early drug genotoxicity screening.It has good application prospects in additional experimental research.