The Application of Organoids in the Study of Antiviral Innate Immunity.

Antiviral innate immunity plays a critical role in the defense against viral infections, yet its complex interactions with viruses have been challenging to study using traditional models. Organoids, three-dimensional (3D) tissue-like structures derived from stem cells, have emerged as powerful tools for modeling human tissues and studying the complex interactions between viruses and the host innate immune system. This chapter summarizes relevant applications of organoids in antiviral innate immunity studies and provides detailed information and experimental procedures for using organoids to study antiviral innate immunity.

Zebrafish as a Model for Investigating Antiviral Innate Immunity.

Zebrafish is a widely used model organism in genetics, developmental biology, pathology, and immunology research. Due to their fast reproduction, large numbers, transparent early embryos, and high genetic conservation with the human genome, zebrafish have been used as a model for studying human and fish viral diseases. In particular, the ability to easily perform forward and reverse genetics and lacking a functional adaptive immune response during the early period of development establish the zebrafish as a favored option to assess the functional implication of specific genes in the antiviral innate immune response and the pathogenesis of viral diseases. In this chapter, we detail protocols for the antiviral innate immunity analysis using the zebrafish model, including the generation of gene-overexpression zebrafish, generation of gene-knockout zebrafish by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, methods of viral infection in zebrafish larvae, analyzing the expression of antiviral genes in zebrafish larvae using qRT-PCR, Western blotting and transcriptome sequencing, and in vivo antiviral assays. These experimental protocols provide effective references for studying the antiviral immune response in the zebrafish model.

In Vitro and In Vivo Evaluation of Virus-Induced Innate Immunity in Mouse.

The innate immune system is the first line of host defense against infection by pathogenic microorganisms, among which macrophages are important innate immune cells. Macrophages are widely distributed throughout the body and recognize and eliminate viruses through pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs). In the present chapter, we provide detailed protocols for vesicular stomatitis virus (VSV) amplification, VSV titer detection, isolation of mouse primary peritoneal macrophages, in vitro and in vivo VSV infection, detection of interferon-beta (IFN-ß) expression, and lung injury. These protocols provide efficient and typical methods to evaluate virus-induced innate immunity in vitro and in vivo.

Applications of mesenchymal stem cell-exosome components in wound infection healing: new insights.

The healing process at a wound is made up of many types of cells, growth factors, the extracellular matrix, nerves and blood vessels all interacting with each other in complex and changing ways. Microbial colonization and proliferation are possible at the place of injury, which makes infection more likely. Because of this, any cut has a chance of getting an infection. Researchers have found that wound infections make patients more upset and cost the healthcare system a lot of money. Surgical site infections happen a lot to people who have recently had surgery. This study shows that such surgical infection is linked to a high rate of illness and death. This is shown by the fact that 25% of patients get serious sepsis and need to be transferred to an intensive care unit. In both animal models and people, mesenchymal stem cells (MSCs) play an active role in all stages of wound healing and have positive effects. Exosomes are one of the main things MSCs release. They have effects that are similar to those of the parent MSCs. Various effector proteins, messenger RNA and microRNAs can be transported by extracellular vesicles to control the activity of target cells. This has a big impact on the healing process. These results suggest that using MSC-exosomes as a new type of cell-free therapy could be a better and safer option than whole cell therapy. This review is mostly about how to use parts of MSC-exosomes to help wound infections heal.

[Transfemoral amputation due to uncontrollable infections after implantation of a total knee endoprosthesis]. / Transfemorale Amputation aufgrund nichtbeherrschbarer Infektionen nach Implantation einer Knietotalendprothese.

INTRODUCTION: In the evaluation of an internal analysis of data on the increased effort for nursing during rehabilitation of patients with amputations in the Baumrainklinik of the HELIOS Rehabilitation Center Bad Berleberg, the number of patients with transfemoral amputations (TFA) due to uncontrollable multiple infections after implantation of a total knee endoprosthesis (total knee arthroplasty, TKA) was clearly emphasized. OBJECTIVE: This article discusses the results of a retrospective, patient-controlled trial (PCT) and compares these with the data of the German Endoprosthesis Registry (EPRD). The study concentrated on patients who were admitted to rehabilitation after a TFA due to an uncontrollable infection after implantation of a knee TKA. The primary aims were the identification of patients who developed an uncontrollable infection after TKA with subsequent TFA and the comparison with national and international revision and amputation rates after TKA. METHOD: An analysis of the medical history questionnaire was carried out for all 787 patients with amputation of the lower extremities who underwent rehabilitation in the time period from 1st January 2007 to 31st December 2015. The patient records were systematically analyzed based on the standardized documentation methods of the medical and nursing personnel using the Barthel index, the activity/function classes, phantom pain and length of stay, including demography, infection history and insurance company. RESULTS: The analysis showed that 10 patients, 2.29% of all TFA, suffered the loss of a lower extremity due to an uncontrollable TKA infection. The revision rate 3 years after primary TKA in Germany is 3.0% (EPRD annual report 2023), whereas values of 1-4% are given in the international literature (status 2020). In the patient group of the EPRD, in 2022 revision surgery was necessary due to an infection in 15.0% of the cases. The current statistics of the EPRD (annual report 2023) show that 3 years after the initial revision surgery due to an infected TKA another revision was necessary in 23.5-30% of cases. CONCLUSION: These numbers are alarming and should be critically evaluated and monitored. The future aim is to identify the causes of infections, systematic errors in the TKA and the pathogens that lead to infections after TKA and to correlate the associations.

[Expert recommendations for the prevention of common respiratory viral infections in neonates]. / æ–°ç”Ÿå„¿å¸¸è§å‘¼å¸é“ç— æ¯’æ„ŸæŸ“é¢„é˜²çš„ä¸“å®¶å»ºè®®.

Neonates, particularly preterm infants, are a susceptible population to respiratory viral infections. Currently, aside from influenza, there are no antiviral medications specifically approved for the treatment of respiratory viral infections in neonates; therefore, prevention of these viral infections is particularly crucial for neonates. The Neonatal HealthCare Committee of Chinese Maternal and Child Health Association, based on domestic and international clinical evidence and combined with clinical practice experience, and after thorough discussion by relevant experts, has developed eight expert recommendations. These include preventive strategies against influenza virus, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus 2 infections, intended for reference in clinical practice.

[Clinical characteristics of Ureaplasma urealyticum infection and colonization in extremely preterm infants]. / è¶ æ—©äº§å„¿è§£è„²è„²åŽŸä½“æ„ŸæŸ“åŠå®šæ¤çŠ¶æ€çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

Chronic Lung Disease as a Risk Factor for Long COVID in Patients Diagnosed With Coronavirus Disease 2019: A Retrospective Cohort Study.

Background: Patients with coronavirus disease 2019 (COVID-19) often experience persistent symptoms, known as postacute sequelae of COVID-19 or long COVID, after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Chronic lung disease (CLD) has been identified in small-scale studies as a potential risk factor for long COVID. Methods: This large-scale retrospective cohort study using the National COVID Cohort Collaborative data evaluated the link between CLD and long COVID over 6 months after acute SARS-CoV-2 infection. We included adults (aged ≥18 years) who tested positive for SARS-CoV-2 during any of 3 SARS-CoV-2 variant periods and used logistic regression to determine the association, considering a comprehensive list of potential confounding factors, including demographics, comorbidities, socioeconomic conditions, geographical influences, and medication. Results: Of 1 206 021 patients, 1.2% were diagnosed with long COVID. A significant association was found between preexisting CLD and long COVID (adjusted odds ratio [aOR], 1.36). Preexisting obesity and depression were also associated with increased long COVID risk (aOR, 1.32 for obesity and 1.29 for depression) as well as demographic factors including female sex (aOR, 1.09) and older age (aOR, 1.79 for age group 40-65 [vs 18-39] years and 1.56 for >65 [vs 18-39] years). Conclusions: CLD is associated with higher odds of developing long COVID within 6 months after acute SARS-CoV-2 infection. These data have implications for identifying high-risk patients and developing interventions for long COVID in patients with CLD.

Asymptomatic Rectal Bacterial Pathogens Show Large Prospective Relationships With HIV Incidence in a Cohort of Young Sexual and Gender Minorities: Implications for STI Screening and HIV Prevention.

Background: We estimated the predictive value of rectal (bacterial sexually transmitted infection [bSTI]) pathogen detection for future HIV seroconversion among young adult sexual and gender minorities (YSGMs) assigned male at birth (AMAB). Methods: Data were collected between March 2018 and August 2022 from RADAR, a longitudinal cohort study of YSGMs AMAB living in the Chicago metropolitan area (n = 1022). Rates of rectal bSTIs and the proportion of self-reported rectal bSTI symptoms are reported. We examined whether the presence of rectal bSTIs predicted HIV seroconversion using generalized estimating equations (GEEs). Results: Participants tested reactive for rectal Mycoplasma genitalium (MGen), Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) at a rate of 20.8 (95% CI, 18.4-23.5), 6.5 (95% CI, 5.0-8.2), and 8.4 (95% CI, 6.8-10.3) cases per 100 persons, respectively. There were no statistically significant pairwise differences in self-reported rectal bSTI symptoms between participants with self-collected swabs testing nonreactive vs reactive for rectal MGen (χ2 = 0.04; P = .84), NG (χ2 = 0.45; P = .37), or CT (χ2 = 0.39; P = .46). In multivariate GEE analysis, rectal NG (adjusted odds ratio, 5.11; 95% CI, 1.20-21.77) was a statistically significant predictor of HIV seroconversion after controlling for other bSTIs, demographics, and sexual risk behavior. Conclusions: Our findings provide a robust longitudinal estimation of the relationship between primarily asymptomatic rectal NG nucleic acid detection and HIV infection. These findings highlight the importance of asymptomatic screening for bSTIs and targeting biobehavioral intervention to prevent HIV infection among YSGMs with rectal bSTI agents detected.

Carrimycin in a Patient with Acute Myeloid Leukemia Complicated with Life-Threatening Mixed Perianal Infection: A Case Report and Literature Review.

Background: Perianal infection has a high incidence and mortality rate in patients with acute myeloid leukemia (AML). Sometimes there is a lack of effective anti-infective treatment regimens. Case Presentation: A 58-year-old male diagnosed with AML presented with secondary perianal infection and septic shock upon admission. Although multiple pathogen cultivation and antibiotic sensitivity tests indicated the presence of sensitive strains, the corresponding antibiotics were ineffective. As a last resort, carrimycin was introduced, ultimately controlling the infection and leading to disease remission. Conclusion: Carrimycin is a complementary treatment option when conventional antibiotic therapy fails. It operates through multiple mechanisms beyond its antibiotic properties and warrants further investigation.

Post-COVID-19 pandemic changes in pertussis incidence among patients with acute respiratory tract infections in Zhejiang, China.

Background: Previous studies have compared the incidence of pertussis before and during the COVID-19 pandemic, finding that public health measures related to COVID-19 contributed to a temporary decline in reported pertussis cases during the pandemic. However, the post-pandemic period has seen a resurgence in respiratory infections, influenced by relaxed health measures and decreased public vigilance. This study investigates the epidemiological dynamics of pertussis among patients with acute respiratory tract infections (ARTI) in Zhejiang Province, China, providing essential reference information for ongoing public health strategies. Methods: This study analyzed multicenter data from January 2023 to May 2024, involving 8,560 patients with ARTI from three hospitals in Zhejiang Province. Inclusion criteria included patients who presented with cough symptoms and were clinically diagnosed with either acute upper respiratory tract infections (URTI) or acute lower respiratory tract infections (LRTI), and who had undergone at least one Bordetella pertussis DNA test. The study analyzed the epidemiological changes of pertussis positivity rates and their associations with time, age, gender, and diagnosis types (URTI and LRTI). Results: From January 2023 to May 2024, the positivity rate and testing number for pertussis among patients with ARTI generally showed a gradual increasing pattern. In March 2024, the positivity rate reached its peak at 31.58%, followed by a weekly decline. The overall positivity rate was 23.59%, with no significant differences observed between genders. Pertussis incidence was higher in patients with LRTI (24.49%) compared to those with URTI (18.63%, OR = 1.40, 95% CI: 1.20-1.63, p < 0.001) and in outpatients (25.32%) compared to inpatients (6.09%, OR = 4.17, 95% CI: 3.07-5.64, p < 0.001). According to a generalized additive model analysis, there was a wave-shaped, non-linear relationship between age and pertussis incidence, with a relatively high rate observed in the 5 to 17 age group, peaking at age 10 (33.85%). Additionally, the impact of age, patient type, and diagnosis type on the pertussis infection rate varied across different age groups. Conclusion: After the COVID-19 pandemic, the positivity rate of pertussis in Zhejiang Province peaked in early 2024 and then showed a declining pattern. Children and adolescents were particularly affected, emphasizing the need for enhanced vaccination and public health interventions in this population.

Active herpesviruses are associated with intensive care unit (ICU) admission in patients pulmonary infection and alter the respiratory microbiome.

Background: The Herpesviridae family contains several human-related viruses, which are able to establish colonizing and latency in the human body, posing a significant threat to the prognosis of patients. Pulmonary infections represent one of the predominant infectious diseases globally, characterized by diverse and multifaceted clinical manifestations that have consistently attracted clinician's concern. However, the relationship of herpesviruses on the prognosis of pulmonary infections and the respiratory microbiota remains poorly understood. Methods: Here, we retrospectively analyzed respiratory samples from 100 patients with pulmonary infection detected by metagenomic next-generation sequencing (mNGS). Results: Employing mNGS, five herpesvirus species were detected: Human alphaherpesvirus 1 (HSV-1), Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), Human betaherpesvirus 7 (HHV-7), and Human betaherpesvirus 6B (HHV-6B). Regression analysis showed that the age and positivity of herpesviruses in patients were independently correlated with ICU admission rates. In addition, positivity of herpesvirus was related with increased ICU days and total hospital stay. The herpesvirus-positive group demonstrated markedly higher incidences of co-infections and fungi-positive, predominantly involving Pneumocystis jirovecii and Aspergillus fumigatus. Analysis of respiratory microbiota revealed a substantially altered community composition within the herpesvirus-positive group, and herpesviruses were significantly positively correlated with the diverse respiratory opportunistic pathogens. Conclusion: Overall results substantiate that the active herpesviruses in patients with pulmonary infections were significantly associated with high ICU admission rate. Moreover, the herpesviruses promotes the dysbiosis of the respiratory microbiota and an increased proportion of co-infections. These insights could contribute to unraveling the underlying mechanisms connecting active herpesviruses to the progression of severe illnesses.

Construction of a risk prediction model for lung infection after chemotherapy in lung cancer patients based on the machine learning algorithm.

Purpose: The objective of this study was to create and validate a machine learning (ML)-based model for predicting the likelihood of lung infections following chemotherapy in patients with lung cancer. Methods: A retrospective study was conducted on a cohort of 502 lung cancer patients undergoing chemotherapy. Data on age, Body Mass Index (BMI), underlying disease, chemotherapy cycle, number of hospitalizations, and various blood test results were collected from medical records. We used the Synthetic Minority Oversampling Technique (SMOTE) to handle unbalanced data. Feature screening was performed using the Boruta algorithm and The Least Absolute Shrinkage and Selection Operator (LASSO). Subsequently, six ML algorithms, namely Logistic Regression (LR), Random Forest (RF), Gaussian Naive Bayes (GNB), Multi-layer Perceptron (MLP), Support Vector Machine (SVM), and K-Nearest Neighbors (KNN) were employed to train and develop an ML model using a 10-fold cross-validation methodology. The model's performance was evaluated through various metrics, including the area under the receiver operating characteristic curve (ROC), accuracy, sensitivity, specificity, F1 score, calibration curve, decision curves, clinical impact curve, and confusion matrix. In addition, model interpretation was performed by the Shapley Additive Explanations (SHAP) analysis to clarify the importance of each feature of the model and its decision basis. Finally, we constructed nomograms to make the predictive model results more readable. Results: The integration of Boruta and LASSO methodologies identified Gender, Smoke, Drink, Chemotherapy cycles, pleural effusion (PE), Neutrophil-lymphocyte count ratio (NLR), Neutrophil-monocyte count ratio (NMR), Lymphocytes (LYM) and Neutrophil (NEUT) as significant predictors. The LR model demonstrated superior performance compared to alternative ML algorithms, achieving an accuracy of 81.80%, a sensitivity of 81.1%, a specificity of 82.5%, an F1 score of 81.6%, and an AUC of 0.888(95%CI(0.863-0.911)). Furthermore, the SHAP method identified Chemotherapy cycles and Smoke as the primary decision factors influencing the ML model's predictions. Finally, this study successfully constructed interactive nomograms and dynamic nomograms. Conclusion: The ML algorithm, combining demographic and clinical factors, accurately predicted post-chemotherapy lung infections in cancer patients. The LR model performed well, potentially improving early detection and treatment in clinical practice.

Statewide Linkage Study of Salmonella Infection and Colorectal Cancer Incidence in Michigan, United States.

Objective: Nontyphoidal Salmonella infection is one of the most common foodborne illnesses, and its oncogenic potential has been documented in animal models. The primary goal of this study was to examine whether individuals who were exposed to enteric Salmonella infection are more likely to develop colorectal cancer (CRC) than the general population through the linkage of 2 statewide public health surveillance databases. Materials and Methods: We designed a 2-stage probabilistic linkage, starting with 17,587 records of enteric salmonellosis reported to Michigan Department of Health and Human Services between 1992 and 2020. These records did not include unique identifiers (such as Social Security number [SSN]). The initial linkage to LexisNexis address history was conducted to obtain information to calculate each person's time in Michigan as well as SSN for the second linkage. The linkage to the state cancer registry was performed to obtain the observed number of CRC cases, while the expected number of CRC cases was calculated according to corresponding state CRC incidence by age, sex, and calendar year. Results: Ninety-three percent of the initially identified salmonellosis records were sent to LexisNexis linkage, which returned address history, death, and SSN for 97% of the records. Further linkage to the statewide cancer registry identified 98 incident CRC cases. Overall, the observed-to-expected (O/E) ratio was not different from unity (0.833; 95% CI, 0.627-1.003). Conclusions: While the new linkage strategy was found effective and should be applicable to other health conditions, we cannot rule out bias due to incomplete or underreporting of the infection in estimating the risk of CRC.

Lactobacillus gasseri associated severe soft tissue infection of the lower extremity: A case report.

Background: Lactobacilli are gram-positive, lactic acid-producing, facultative anaerobes of the human microbiota located in the human gastrointestinal tract, genitourinary tract, and the oral cavity and are considered non-pathogenic. When certain risk factors are present, they have the potential to cause serious infections. The incidence of localized infections associated with Lactobacilli are rare and to our knowledge we present the first known case of severe soft tissue infection of the extremity linked to a Lactobacillus strain. Case presentation: We describe the case of a 41-year-old man with a history of type 2 Diabetes Mellitus (DM), arterial hypertension and schizophrenia, who was admitted for weakness, high fever of 39.7 °C (103.5°F) and an abscess formation of the left thigh caused by an infection with Lactobacillus gasseri (L.gasseri). Conclusion: While infections caused by Lactobacilli are rare, it is crucial not to underestimate the potential of typically non-pathogenic bacteria like L. gasseri to act as infectious agents in immunocompromised patients. Abscess drainage and antibiotic treatment were successful treatment strategies for this rare case of soft tissue infection cause by L.gasseri.

Reconstruction of a Submandibular Soft Tissue Defect with a Temporoparietal Fasciocutaneous Flap - A Case Report.

Rationale: Reconstruction of soft tissue defects in the facial region have always been challenging. Appropriate selection of flaps will result in minimal morbidity and restore the tissue form without compromising function. Patient Concerns: During reconstruction in the facial region, patients desire to have minimal visible scar and functions of the jaw bone. Diagnosis: The article discusses a case of right space infection with soft tissue loss in the submandibular region. Treatment: The fascial spaces were explored and the odontogenic foci of infection were removed. The soft tissue defect in the submandibular region was resurfaced using the temporoparietal fasciocutaneous flap. Outcomes: The flap was well settled, and facial contours were maintained with reasonable facial symmetry. Take-away Lessons: Surgical skill in the management of soft tissue defects in the fascial region demands sound knowledge of the facial region, selection of the flap and meticulous execution of the surgical plan.

Impact of TAS2R38 polymorphisms on nasal nitric oxide and Pseudomonas infections in primary ciliary dyskinesia: relation to genotype.

OBJECTIVE: Primary ciliary dyskinesia (PCD) severity has been related to genotype and levels of nasal nitric oxide (nNO). The most common TAS2R38 haplotypes (PAV/PAV, PAV/AVI, AVI/AVI) encoding the bitter taste receptor can affect nNO levels and thus could play a role in the susceptibility to respiratory infections. We assessed the impact of these polymorphisms on nNO production and Pseudomonas aeruginosa (P.a.) infections in different PCD genotypes. METHODS: Prospective, longitudinal, single-centre study in patients with PCD with known genotype and one of three TAS2R38 haplotypes evaluated for up to 10 years. We related nNO values to TAS2R38 haplotypes in all patients, and in the three most frequent genotypes (CCDC39/CCDC40, DNAH5, DNAH11). In the genetic group(s) with different mean trends of nNO in relation to the polymorphism, we evaluated longitudinal lung function as a clinical outcome measure. We also studied any associations between the prevalence of chronic P.a. infection and PAV alleles. Linear mixed-effects models were used to evaluate longitudinal associations. RESULTS: 119 patients with PCD underwent 1116 study visits. Only in the DNAH11 mutations group was there a mean trend of nNO production which was significantly higher in PAV/PAV than AVI/AVI haplotype (p=0.033), with a better trend in spirometric and plethysmographic parameters. In patients with DNAH11 mutations the PAV allele was also associated with a significantly reduced prevalence of chronic P.a. CONCLUSION: TAS2R38 may be a modifier gene for PCD severity, but only in mild phenotype disease. Further study of TAS2R38 polymorphisms might enable new management strategies to prevent chronic P.a.

Unmasking the hidden impact of viruses on tuberculosis risk.

Tuberculosis (TB) is a leading cause of mortality from an infectious disease. In this opinion article, we focus on accumulating scientific evidence indicating that viral infections may contribute to TB progression, possibly allowing novel preventive interventions. Viruses can remodel the mammalian immune system, potentially modulating the risk of reactivating latent microbes such as Mycobacterium tuberculosis (Mtb). Evidence is mixed regarding the impact of emergent viruses such as SARS-CoV-2 on the risk of TB. Therefore, we posit that important knowledge gaps include elucidating which viral families increase TB risk and whether these provide unique or shared immune mechanisms. We also propose potential future research to define the contribution of viruses to TB pathogenesis.

Polydopamine-assisted smart bacteria-responsive hydrogel: Switchable antimicrobial and antifouling capabilities for accelerated wound healing.

INTRODUCTION: Wound infections and formation of biofilms caused by multidrug-resistant bacteria have constituted a series of wound deteriorated and life-threatening problems. The in situ resisting bacterial adhesion, killing multidrug-resistance bacteria, and releasing dead bacteria is strongly required to supply a gap of existing sterilization strategies. OBJECTIVES: This study aims to present a facile approach to construct a bacteria-responsive hydrogel with switchable antimicrobial-antifouling properties through a "resisting-killing-releasing" method. METHODS: The smart bacteria-responsive hydrogel was constructed by two-step immersion strategy: a simple immersion-coating process to construct Polydopamine (pDA) coatings on the surface of a gelatin-chitosan composite hydrogel and followed by grafting of bactericidal quaternary ammonium chitosan (QCS) as well as pH-responsive PMAA to this pDA coating. The in vitro antimicrobial activity, biocompatibility and the in vivo wound healing effects in a mouse MRSA-infected full-thickness defect model of the hydrogel were further evaluated. RESULTS: Assisted by polydopamine coating, the pH-responsive PMAA and bactericidal QCS are successfully grafted onto a gelatin-chitosan composite hydrogel surface and hydrogels maintain the adequate mechanical properties. At physiological conditions, the PMAA hydration layer endows the hydrogel with resistance to initial bacterial attachment. Once bacteria colonize and acidize local environment, the swelling PMAA chains tend to collapse then expose the bactericidal QCS, realizing the on-demand kill bacteria. Moreover, the dead bacteria can be released and the hydrogel will resume the resistance due to hydrophilicity of PMAA at increased pH, endowing the surface renewable ability. In vitro and in vivo studies demonstrate the favorable biocompatibility and wound healing capacity of hydrogels that can inhibit infection and further facilitate granulation tissue, angiogenesis, and collagen synthesis. CONCLUSION: This strategy provides a novel methodology for the development and design of smart wound dressing to combat multidrug-resistant bacteria infections.

A novel infrared spectroscopy marker for assessing the postoperative infection risk in patients with upper urinary tract calculus.

The aim of this study is to evaluate the ability of infrared wavenumber of calculus to predict postoperative infection in patients with upper urinary tract calculus (UUTC), and to establish a predictive model based on this. From March 2018 to March 2023, 480 UUTC patients from Fujian Provincial Hospital were included in this study. The infrared-wavenumbers related infection score (IR-infection score) was constructed by univariate analysis, multicollinearity screening, and Lasso analysis to predict postoperative infection. Continually, the Delong test was used to compare the predictive power between the IR-infection score and traditional indicators. Afterward, we performed urine metagene sequencing and stone culture to prove the correlation between calculus toxicity and IR-infection score. Finally, logistic regression was used to build a nomogram. IR-infection score composed of four independent wavenumbers could precisely predict postoperative infection (AUCvalidation cohort = 0.707) and sepsis (AUCvalidation cohort = 0.824). IR-infection score had better predictive ability than commonly used clinical indicators. Moreover, metagenomics sequencing and calculus culture confirmed the correlation between IR-infection score and calculus toxicity (all P < 0.05). The nomogram based on the IR-infection score had high predictive power (all AUCs > 0.803). Our study first developed a novel infrared spectroscopy marker and nomogram, which can help urologists better predict postoperative infection in UUTC patients.