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 explore the clinical efficacy and safety of early surgical treatment for spinal thoracolumbar fracture without nerve injury.Methods The clinical data of 80 patients with spinal thoracolumbar fracture without nerve injury who were admitted to the department of spinal surgery in our hospital were retrospectively analyzed.According to the different operation timing,those who underwent surgery within 72 hours after fracture were included in the early operation group(n=41),and those who underwent surgery 72 hours to 2 weeks after fracture were included in the elective operation group(n=39).All operations were performed through the Wiltse approach for short-segment pedicle screw fixation on the injured vertebra.The operation time,intraoperative blood loss,hospital stay and incidence of complication of the two groups were compared.The visual analogue scale(VAS)scores,Oswestry disability index(ODI),compression rate of the anterior edge height of the injured vertebra,and the Cobb angle in the sagittal position of the injured vertebra before surgery,1 week after surgery and 1 year after surgery were compared between the two groups.The improvement rates of the anterior edge height compression and the Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery were compared between the two groups.Results There was no significant difference in the operation time,intraoperative blood loss or total incidence of complications between the two groups(P>0.05).The hospital stay in the early operation group was shorter than that in the elective operation group,and the difference was statistically significant(P<0.05).The VAS scores and ODI 1 week and 1 year after surgery of the two groups were better than those before surgery,and the differences were statistically significant(P<0.05).There was no significant difference in the VAS scores or ODI at each time point before and after surgery between the two groups(P>0.05).The compression rate of the anterior edge height and Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the two groups were lower/smaller than those before surgery,with statistically significant differences(P<0.05).There was no statistically significant difference in the compression rate of the anterior edge height or Cobb angle before surgery in the sagittal position of the injured vertebrae between the two groups(P>0.05).The compression rate of the anterior edge height and Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the early operation group were lower/smaller than those in the elective operation group,and the differences were statistically significant(P<0.05).The improvement rates of the anterior edge height compression and the Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the early operation group were better than those in the elective operation group,and the differences were statistically significant(P<0.05).Conclusion Early surgical treatment for spinal thoracolumbar fracture without nerve damage is safe,it can significantly shorten hospitalization time,obtain good fracture reduction quality and definite therapeutic effects.However,a comprehensive preoperative evaluation of the patients' condition is necessary to ensure surgical safety.

Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100％.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80％.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.

Despite significant advancements in treatments for heart failure,the overall prognosis for patients remains poor.Hemodynamic abnormalities in heart failure manifest as elevated left atrial pressure and pulmonary congestion.Previous studies have shown that reducing left atrial pressure can improve symptoms and prognosis for heart failure patients,suggesting that left-sided heart overload may be a potential target for heart failure treatment.Atrial shunting procedures aim to create a stable and controlled left-to-right intracardiac shunt,restoring the decompensated left heart volume and pressure load in heart failure patients to a compensatory state,thereby improving heart failure symptoms and prognosis.Currently,this treatment is still in the clinical research stage globally.Existing data indicate that atrial shunting procedures can lower left atrial pressure at rest or during exercise in heart failure patients,improve pulmonary congestion,enhance patients'exercise tolerance,and clinical cardiac function.However,no studies have yet confirmed that it can improve clinical endpoints such as rehospitalization and mortality due to heart failure.Future research will focus on identifying heart failure patients who may benefit from atrial shunting,with assessments of heart failure etiology,right heart function,and reversibility of pulmonary vascular resistance,as well as heart failure classification based on ejection fraction,serving as potential key factors for patient selection.

This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 μmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 μmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 μmol·L~(-1) BAI significantly increased the SOD activity and 5 μmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1β, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.
Humans ; NF-kappa B/metabolism* ; Microglia ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Lipopolysaccharides/pharmacology* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Superoxide Dismutase/metabolism*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVES: To study the clinical and bronchoscopic characteristics of tracheobronchial tuberculosis (TBTB) in children and to identify factors influencing residual airway obstruction or stenosis. METHODS: The clinical data of children with TBTB were retrospectively collected. The children were divided into two groups based on the last bronchoscopic result within one year of follow-up: a group with residual airway obstruction or stenosis (n=34) and a group without residual airway obstruction or stenosis (n=58). A multivariate logistic regression analysis was used to identify the factors influencing residual airway obstruction or stenosis in children with TBTB. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the factors influencing residual airway obstruction or stenosis in children with TBTB. RESULTS: A total of 92 children with TBTB were included, and the main symptoms were cough (90%) and fever (68%). In children under 1 year old, the incidence rates of dyspnea and wheezing were significantly higher than in other age groups (P<0.008). Chest CT findings included mediastinal or hilar lymph node enlargement (90%) and tracheobronchial stenosis or obstruction (61%). The lymphatic fistula type was the main type of TBTB observed bronchoscopically (77%). All children received interventional treatment, and the effective rate was 84%. During one year of follow-up, 34 children had residual airway obstruction or stenosis. The TBTB diagnostic time and the initiation of interventional treatment were significantly delayed in the group with residual airway obstruction or stenosis compared with the group without residual airway obstruction or stenosis (P<0.05). The multivariate logistic regression analysis showed that the TBTB diagnostic time was closely related to residual airway obstruction or stenosis in children (P<0.05). ROC curve analysis showed that at the cut-off value of 92 days of TBTB diagnostic time, the area under the curve for predicting residual airway obstruction or stenosis in children with TBTB was 0.707, with a sensitivity of 58.8% and a specificity of 75.9%. CONCLUSIONS The clinical manifestations of TBTB are nonspecific, and symptoms are more severe in children under 1 year old. TBTB should be suspected in children with tuberculosis and chest imaging indicating airway involvement. Delayed diagnosis of TBTB is associated with the development of residual airway obstruction or stenosis.
Infant ; Child ; Humans ; Bronchoscopy/methods* ; Constriction, Pathologic/complications* ; Bronchial Diseases/therapy* ; Retrospective Studies ; Tuberculosis/diagnosis* ; Airway Obstruction/therapy*

OBJECTIVES: To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. METHODS: This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. RESULTS: A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). CONCLUSIONS Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.
Female ; Male ; Child ; Humans ; Child, Preschool ; Multiple Organ Failure ; Retrospective Studies ; Bronchitis/etiology* ; Dyspnea ; Pleural Effusion ; Pulmonary Atelectasis ; Plastics ; Respiratory Insufficiency

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Objective: To compare the safety and efficacy of different anticoagulants in patients with indications for anticoagulation after transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Patients who underwent TAVR from April 2016 to February 2022 in Guangdong Provincial People's Hospital and had indications for anticoagulation were included and divided into two groups according to the type of anticoagulants, i.e. non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin, and patients were followed up for 30 days. The primary endpoint was the combination of death, stroke, myocardial infarction, valve thrombosis, intracardiac thrombosis and major bleeding. The incidence of endpoints was compared between two groups, and multivariate logistic regression analysis was applied to adjust the bias of potential confounders. Results: A total of 80 patients were included. Mean age was (74.4±7.1) years, 43 (53.8%) were male. Forty-nine (61.3%) patients used NOAC, 31 used warfarin, and major indication for anticoagulants was atrial fibrillation (76/80, 95.0%). The adjusted risks of the primary endpoint (OR=0.23, 95%CI 0.06-0.94, P=0.040) of NOAC were lower than that of warfarin, mainly driven by a lower risk of major bleeding (OR=0.19, 95%CI 0.04-0.92, P=0.039). Conclusions: The short-term outcome of NOAC is better than that of warfarin in patients with indications for anticoagulation after TAVR. Randomized controlled trials of large sample size with long-term follow-up are needed to further testify this finding.
Humans ; Male ; Aged ; Aged, 80 and over ; Female ; Anticoagulants/therapeutic use* ; Warfarin/therapeutic use* ; Transcatheter Aortic Valve Replacement ; Retrospective Studies ; Hemorrhage ; Stroke/epidemiology* ; Atrial Fibrillation/drug therapy* ; Treatment Outcome ; Administration, Oral