Pathogen-specific alterations in intestinal microbiota precede urinary tract infections in preterm infants: a longitudinal case-control study.

Urinary tract infections (UTIs) are among the most common late-onset infections in preterm infants, characterized by nonspecific symptoms and a pathogenic spectrum that diverges from that of term infants and older children, which present unique diagnostic and therapeutic challenges. Existing data on the role of gut microbiota in UTI pathogenesis in this demographic are limited. This study aims to investigate alterations in gut microbiota and fecal calprotectin levels and their association with the development of UTIs in hospitalized preterm infants. A longitudinal case-control study was conducted involving preterm infants admitted between January 2018 and October 2020. Fecal samples were collected weekly and analyzed for microbial profiles and calprotectin levels. Propensity score matching, accounting for key perinatal factors including age and antibiotic use, was utilized to match samples from UTI-diagnosed infants to those from non-UTI counterparts. Among the 151 preterm infants studied, 53 were diagnosed with a UTI, predominantly caused by Enterobacteriaceae (79.3%) and Enterococcaceae (19.0%). Infants with UTIs showed a significantly higher abundance of these families compared to non-UTI infants, for both Gram-negative and positive pathogens, respectively. Notably, there was a significant pre-UTI increase in the abundance of pathogen-specific taxa in infants later diagnosed with UTIs, offering high predictive value for early detection. Shotgun metagenomic sequencing further confirmed the dominance of specific pathogenic species pre-UTI and revealed altered virulence factor profiles associated with Klebsiella aerogenes and Escherichia coli infections. Additionally, a decline in fecal calprotectin levels was observed preceding UTI onset, particularly in cases involving Enterobacteriaceae. The observed pathogen-specific alterations in the gut microbiota preceding UTI onset offer novel insight into the UTI pathogenesis and promising early biomarkers for UTIs in preterm infants, potentially enhancing the timely management of this common infection. However, further validation in larger cohorts is essential to confirm these findings.

Associations of Early Gut Microbiome and Metabolome with Growth and Body Composition of Preterm Infants Within the First 6 Months.

Objectives: This study aimed to explore the associations of growth and body composition with gut microbiome and metabolome in preterm infants. Materials and Methods: A prospective cohort study including 73 human milk-fed very preterm infants was conducted. During hospitalization, fecal samples were collected to detect microbes and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Growth and body composition indices were measured at term equivalent age (TEA) and 6 months of corrected age (CA). Associations of the fecal microbiome and metabolome profiles with growth and body composition indices, as well as their changes, were analyzed. Results: A higher abundance of Streptococcus was associated with a lower fat-free mass (FFM) z-score at 6 months of CA (p = 0.002) and a smaller increase in FFM z-score from TEA to 6 months of CA (p = 0.018). Higher levels of 3'-sialyllactose and 6'-sialyllactose (6'-SL) in feces were correlated with a lower z-score of percentage body fat (PBF) (p = 0.018 and 0.020, respectively) and a lower z-score of fat mass (p = 0.044 and 0.043, respectively) at 6 months of CA. A higher level of 6'-SL in feces was correlated with a greater increase in FFM z-score from TEA to 6 months of CA (p = 0.021). Conclusions: This study sheds light on the role of specific microbial-host interactions in metabolic changes in preterm infants, indicating the potential role of sialylated human milk oligosaccharides in optimizing body composition.

A rumen-derived bifunctional glucanase/mannanase uncanonically releases oligosaccharides with a high degree of polymerization preferentially from branched substrates.

Glycoside hydrolases (GHs) are known to depolymerize polysaccharides into oligo-/mono-saccharides, they are extensively used as additives for both animals feed and our food. Here we reported the characterization of IDSGH5-14(CD), a weakly-acidic mesophilic bifunctional mannanase/glucanase of GH5, originally isolated from sheep rumen microbes. Biochemical characterization studies revealed that IDSGH5-14(CD) exhibited preferential hydrolysis of mannan-like and glucan-like substrates. Interestingly, the enzyme exhibited significantly robust catalytic activity towards branched-substrates compared to linear polysaccharides (P < 0.05). Substrate hydrolysis pattern indicated that IDSGH5-14(CD) predominantly liberated oligosaccharides with a degree of polymerization (DP) of 3-7 as the end products, dramatically distinct from canonical endo-acting enzymes. Comparative modeling revealed that IDSGH5-14(CD) was mainly comprised of a (ß/α)8-barrel-like structure with a spacious catalytic cleft on surface, facilitating the enzyme to target high-DP or branched oligosaccharides. Molecular dynamics (MD) simulations further suggested that the branched-ligand, 64-α-D-galactosyl-mannohexose, was steadily accommodated within the catalytic pocket via a two-sided clamp formed by the aromatic residues. This study first reports a bifunctional GH5 enzyme that predominantly generates high-DP oligosaccharides, preferentially from branched-substrates. This provides novel insights into the catalytic mechanism and molecular underpinnings of polysaccharide depolymerization, with potential implications for feed additive development and high-DP oligosaccharides preparation.

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Dynamics and Crosstalk between Gut Microbiota, Metabolome, and Fecal Calprotectin in Very Preterm Infants: Insights into Feeding Intolerance.

BACKGROUND: Feeding intolerance (FI) is a significant concern in the care of preterm infants, impacting their growth and development. We previously reported that FI is linked to lower fecal calprotectin (FC) levels. This study aims to explore the postnatal dynamics and interplay between microbiota, metabolic profiles, and host immunity in preterm infants with and without FI. METHODS: Infants with gestational age <32 weeks or birth weight <1500 g were enrolled at the Children's Hospital of Fudan University between January 2018 and October 2020. Weekly fecal samples were analyzed for bacterial profiling, metabolome, and calprotectin levels, exploring their longitudinal development and interrelationships. RESULTS: Of the 118 very preterm infants studied, 48 showed FI. These infants experienced an interrupted microbial-immune trajectory, particularly at 3-4 weeks of age, marked by a reduced bacterial abundance, alpha diversity, and FC levels. Metabolic changes in FI were pronounced between 3 and 6 weeks. Pantothenic acid and two polyamine metabolites were closely associated with bacterial abundance and FC levels and negatively correlated with the duration to attain full enteral feeding. CONCLUSIONS: FI infants demonstrated compromised microbiome-immune interactions, potentially influenced by specific metabolites. This research underscored the importance of early microbial and metabolic development in the pathogenesis of FI in very preterm infants.

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The male patient was referred to the hospital at 44 days old due to dyspnea after birth and inability to wean off oxygen. His brother died three days after birth due to respiratory failure. The main symptoms observed were respiratory failure, dyspnea, and hypoxemia. A chest CT scan revealed characteristic reduced opacity in both lungs with a "crazy-paving" appearance. The bronchoalveolar lavage fluid (BALF) showed periodic acid-Schiff positive proteinaceous deposits. Genetic testing indicated a compound heterozygous mutation in the ABCA3 gene. The diagnosis for the infant was congenital pulmonary alveolar proteinosis (PAP). Congenital PAP is a significant cause of challenging-to-treat respiratory failure in full-term infants. Therefore, congenital PAP should be considered in infants experiencing persistently difficult-to-treat dyspnea shortly after birth. Early utilization of chest CT scans, BALF pathological examination, and genetic testing may aid in early diagnosis.

Sepsis induces non-classic innate immune memory in granulocytes.

Secondary infection in patients with sepsis triggers a new wave of inflammatory response, which aggravates organ injury and increases mortality. Trained immunity boosts a potent and nonspecific response to the secondary challenge and has been considered beneficial for the host. Here, using a murine model of polymicrobial infection, we find that the primary infection reprograms granulocytes to boost enhanced inflammatory responses to the secondary infection, including the excessive production of inflammatory cytokines, respiratory burst, and augmented phagocytosis capacity. However, these reprogramed granulocytes exhibit "non-classic" characteristics of innate immune memory. Two mechanisms are independently involved in the innate immune memory of granulocytes: a metabolic shift in favor of glycolysis and fatty acid synthesis and chromatin remodeling leading to the transcriptional inactivity of genes encoding inhibitors of TLR4-initiated signaling pathways. Counteracting the deleterious effects of stressed granulocytes on anti-infection immunity might provide a strategy to fight secondary infections during sepsis.

Postnatal Dynamics and Clinical Associations of Fecal Calprotectin in Very Preterm Infants: Implications for Necrotizing Enterocolitis and Feeding Intolerance.

INTRODUCTION: To elucidate the postnatal dynamics and clinical associations of fecal calprotectin (FC) in very preterm infants, with a focus on necrotizing enterocolitis (NEC) and feeding intolerance (FI). METHODS: We performed a prospective observational cohort study in infants with a gestational age of <32 weeks or birth weight <1,500 g with weekly feces collection. The relationships between FC, NEC, and FI were investigated, adjusting for demographic and clinical factors. RESULTS: A total of 1,086 fecal samples were collected from 194 preterm infants. Postnatal FC levels of non-NEC infants were highly variable and followed an age-dependent patterned progression. FC levels were elevated in patients with NEC before and at NEC onset, distinguishing them from non-NEC infants and those at sepsis onset. Among infants without NEC or sepsis, those with FI exhibited lower FC concentrations throughout hospitalization and displayed a significant delay in reaching high FC levels after meconium compared with non-FI infants. The age to reach the first high nonmeconial FC levels was positively associated with the time to achieve full enteral feeding. DISCUSSION: Postnatal FC dynamics among premature infants followed a patterned progression but were disturbed in patients with NEC and FI. Because of the high variations, the use of FC levels in NEC diagnosis should be implemented with caution in clinical practice. FC may help understand FI and feeding progression in very preterm infants. Further research is needed to validate these findings and explore the potential clinical applications of FC in this population.

Soluble ST2 predicts continuous renal replacement therapy in patients receiving venoarterial extracorporeal membrane oxygenation.

OBJECTIVE: This study aimed to evaluate the relationship between plasma soluble ST2 (sST2) levels 24 h after extracorporeal membrane oxygenation (ECMO) initiation and continuous renal replacement therapy (CRRT) in patients receiving venoarterial ECMO (V-A ECMO) support. METHODS AND RESULTS: Data of patients who received ECMO support for postcardiotomy cardiogenic shock between January 2017 and July 2019 were retrospectively collected from Beijing Anzhen Hospital, Capital Medical University. Ultimately, 116 patients were included in the present study for analysis. The concentration of sST2 was determined by enzyme-linked immunosorbent assay (ELISA). The log10 sST2 levels were higher in patients undergoing CRRT than those who did not (6.06 vs. 6.22, p = 0.019). Patients undergoing CRRT had a lower survival rate than those who did not (32.8% vs. 67.3%, p < 0.001). In the univariate logistic regression analysis, sST2, HCO3-, lactate, and creatinine levels 24 h after ECMO initiation were related to CRRT (p < 0.05). In the multivariate logistic regression analysis, HCO3- and sST2 were identified as independent risk factors for CRRT use in patients undergoing ECMO (p < 0.05). The area under receiver operator characteristic curve (AUC) for sST2 and HCO3- together was 0.72 (95% confidence interval (CI), 0.79-0.91), which was better than those of sST2 or HCO3- alone (0.63 vs. 0.67). CONCLUSIONS: sST2 and HCO3-levels at 24 h after ECMO initiation were associated with CRRT and could predict CRRT use in postcardiotomy cardiogenic shock patients undergoing ECMO.

Metabolism-dependent ferroptosis promotes mitochondrial dysfunction and inflammation in CD4+ T lymphocytes in HIV-infected immune non-responders.

BACKGROUND: HIV immune non-responders (INRs) are described as a failure to reestablish a pool of CD4+ T lymphocytes (CD4 cells) after antiretroviral therapy (ART), which is related to poor clinical results. Ferroptosis is a newly discovered form of cell death characterised by iron-dependent lipid peroxidation and the accumulation of reactive oxygen species (ROS). The mechanism of unrecoverable CD4 cells in INRs and whether ferroptosis plays a role are not fully understood. METHODS: Ninety-two people living with HIV (PLHIVs) who experienced four-year ART with sustained viral suppression, including 27 INRs, 34 partial responders (PRs), and 31 complete responders (CRs); and 26 uninfected control participants (UCs) were analysed for 16 immune parameters with flow cytometry. Then plasma lipid, iron and oxidation, and antioxidant indicators were detected by ELISA, and CD4 cells were sorted out and visualised under transmission electron microscopy. Finally, ferroptosis inhibitors were added, and alterations in CD4 cell phenotype and function were observed. FINDINGS: We found decreased recent thymic emigrants (RTE), over-activation and over-proliferation phenotypes, diminished killing function, decreased IL-7R and more severe inflammation; increased lipid peroxidation in the mitochondria and disruptions of the mitochondrial structure, showing typical features of ferroptosis in CD4 cells in INRs. Additionally, ferroptosis inhibitors could reduce inflammation and repair mitochondrial damage. Meanwhile, ELISA results showed increased plasma free fatty acids (FFA) and an imbalance of oxidative and antioxidant systems in INRs. Flow cytometry results displayed alterations of both transferrin receptor (CD71) and lipid transporter (CD36) expressions on the surface of CD4 cells. Mechanistically, there was a stronger correlation between CD36 expression and mitochondrial lipid peroxidation production, ferroptosis makers, and inflammation indicators; while amino acid transporter (CD98) was more related to killing functions; and CD71 was more closely related to activation status in CD4 cells. INTERPRETATION: Cellular metabolism was closely correlated with its diverse functions in INRs. Ferroptosis was observed in CD4 cells of INRs, and inhibiting ferroptosis through modulating mitochondrial disorders and inflammation may offer an alternative immunological strategy for reinvigorating CD4 cells in INRs. FUNDING: This research was supported by the 13th Five-year Plan, Ministry of Science and Technology of China (2018ZX10302-102), Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20191802), and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX202126).

Elucidating the Gene Signatures and Immune Cell Types in HIV-Infected Immunological Non-Responders by Bioinformatics Analyses.

Objective: Numerous studies have reported on the pathogenesis of poor immune reconstitution (PIR) after antiretroviral treatment in human immunodeficiency virus (HIV) patients. However, fewer studies focused on both immune-related genes (IRGs) and immune cells, and the correlation between IRGs and immune cells was evaluated via bioinformatics analyses. Methods: Gene expression profiling of GSE143742 from the Gene Expression Omnibus (GEO) database was analyzed to get differentially expressed immune-related genes (DEIRGs). The enrichment analysis and protein-protein interaction (PPI) networks of DEIRGs were established. The relative fractions of 22 immune cell types were detected using the "CIBERSORT". The correlation analysis between DEIRGs and immune cells was constructed to discover the potential IRGs associated with immune cells. A logistic regression diagnostic model was built, and a receiver operating characteristic (ROC) curve was performed to evaluate the model's diagnostic efficacy. The CMap database was used to find molecules with therapeutic potential. RT-qPCR was used to verify the expression of the hub DEIRGs. Results: We identified eight types of significantly changed immune cells and five hub IRGs in INRs. The DEIRGs were mainly enriched in lymphocyte activation, receptor-ligand activity, and T cell receptor signaling pathway. The correlation analysis showed that the expression of TNF, CXCR4 and TFRC correlate with CD8 cells, resting mast cells, activated NK cells, and naïve CD4 cells in INRs. Meanwhile, TFRC and IL7R relate to activated NK cells and resting memory CD4 cells respectively in IRs. A diagnostic model was constructed using multiple logistic regression and nine small molecules were identified as possible drugs. Conclusion: In this study, we suggested that the process of PIR might be related to TNF, CXCR4, TFRC, CD48, and IL7R. And these IRGs play roles in regulating immune-competent cells. And our constructed diagnostic model has excellent effectiveness. Moreover, some small-molecule drugs are screened to alleviate PIR.

Phenotypic and functional alterations of monocyte subsets with aging.

BACKGROUND: It has been widely accepted that monocytes are one of the central mediators contributing to inflammaging. However, it remains unclear whether aged monocytes, similar to aged T cells, have characteristics of hyperactivation and increased expression of co-inhibitory molecules. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from young (21-40 years old), middle-aged (41-60 years old), and older human subjects (> 60 years old). Flow cytometry was used to monitor changes in the expression of surface molecules of monocyte subsets and cytokine-producing capacity. RESULTS: We observed increased tumor necrosis factor-α: TNF-α and decreased interleukin-6 (IL-6) production in monocytes from older adults compared with young and middle-aged adults. Older adults had a greater percentage of intermediate and non-classical monocyte subsets, along with increased levels of the immune activation markers human leukocyte antigen-DR (HLA-DR), and adhesion molecules cluster of differentiation molecule 11b (CD11b) and L-selectin (CD62L). Furthermore, we observed increased C-C motif chemokine receptor 2 (CCR2) expression on classical monocytes and decreased C-X3-C motif chemokine receptor 1 (CX3CR1) expression on non-classical monocytes in older adult subjects. The expression of co-inhibitory receptors was reduced on monocyte subsets in older adults. CONCLUSIONS: Circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.

Trends in rates and causes of hospitalization among people living with HIV in the antiretroviral therapy era: A retrospective cohort study in China, 2008-2020.

Background: The introduction of antiretroviral therapy (ART) has resulted in marked reductions in morbidity among people living with HIV (PLWH). Monitoring the hospitalizations of PLWH is important in evaluating the quality of healthcare and forecasting the co-morbidity pattern. We aimed to describe the trends in the rates and causes of hospitalization among PLWH who initiated ART in an HIV-designated hospital in China. Methods: PLWH who initiated ART and were hospitalized in Beijing Ditan Hospital from 2008 to 2020 were selected for the study. Hospitalizations were classified based on AIDS-defining events (ADEs), non-AIDS-defining events (nADEs), and other causes. Hospitalization rates were calculated in terms of person-years, with risk factors determined by Poisson regression. The proportion of hospitalization causes at different ART treatment statuses was also evaluated. Results: A total of 9,404 patients (94.7% were male patients) were included, contributing to 49,419 person-years. Overall, 1,551 PLWH were hospitalized for 2,667 hospitalization events, among which 60.4% of hospitalizations were due to ADEs, 11.4% were due to nADEs, and 28.2% were due to other causes. Unadjusted hospitalization rates decreased for all causes and all three diagnostic categories with year. After adjusting for the variables that changed substantially over time, ADE-related [IRR, 1.01 (0.96-1.05)] and nADE-related hospitalization rates [IRR, 0.92 (0.84-1.01)] appeared stable. Hospitalization for ADEs constituted an increasing proportion over time (36.3% in 2008-57.4% in 2020), especially in ART-naive inpatients (43.8% in 2008-83.3% in 2020). The proportion of nADE-related hospitalizations remained low (9.0% in 2008-15.4% in 2020). Hospitalization rate was highest for patients treated with ART during the first 6 months after ART initiation (46.2%) when ADEs were still the leading cause of hospitalizations (30.6%). Older age, non-men who have sex with men transmission, late presenters, HIV viral load (VL) > 50 copies/mL, and CD4 counts ≤ 200 cells/µL were associated with a higher hospitalization risk (all P < 0.05). Conclusion: Despite some progress, ADEs remain the most common and serious problem among PLWH in China. In order to avoid deteriorating to the stage of needing hospitalization, more work is needed to diagnose and treat HIV infection earlier.

Anxiety, depression, and sleep disturbances among people on long-term efavirenz-based treatment for HIV: a cross-sectional study in Beijing, China.

BACKGROUND: Efavirenz (EFV)-induced neuropsychiatric toxicity bothers people living with HIV (PLHIV). Neuropsychiatric adverse effects of EFV may differ by length of time on EFV-based antiretroviral treatment (ART). METHODS: A cross-sectional, single-center study was conducted at Beijing Ditan Hospital in China from June-August 2020 among ART-experienced PLHIV who were on long-term EFV-based ART. 424 eligible virological suppressed participants were enrolled and divided into four groups according to time on EFV-based ART: group A (0.5 ≤ ART < 2 year), B (2 ≤ ART < 4 year), C (4 ≤ ART < 6 year), and D (ART ≥ 6 year). The questionnaires about 12-item Short Form Health Survey (SF-12), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) were administered to assess neuropsychiatric adverse events of EFV among different groups. RESULTS: Overall mental component summary scores (MCS) of SF-12 in PLHIV was 50.2, which was lower than general population. Overall prevalence of anxiety, depression and sleep disturbances was 15.6%, 15.3% and 58%, respectively. Prevalence of anxiety, depression and sleep disturbances did not vary significantly between the time-on-ART groups. Anxiety, depression, sleep disturbances had no correlation with time on EFV-based ART or CD4+ T cells counts. CONCLUSIONS: In ART-experienced PLHIV in China, neuropsychiatric adverse events exist persistently and prevalence do not significantly change with prolonged time on EFV-based ART. The prevalence of sleep disturbances was high, suggesting that clinicians should pay more attention to long-standing psychiatric health to perform early and effective interventions.

A real-time driver fatigue identification method based on GA-GRNN.

It is of great practical and theoretical significance to identify driver fatigue state in real time and accurately and provide active safety warning in time. In this paper, a non-invasive and low-cost method of fatigue driving state identification based on genetic algorithm optimization of generalized regression neural network model is proposed. The specific work is as follows: (1) design simulated driving experiment and real driving experiment, determine the fatigue state of drivers according to the binary Karolinska Sleepiness Scale (KSS), and establish the fatigue driving sample database. (2) Improved Multi-Task Cascaded Convolutional Networks (MTCNN) and applied to face detection. Dlib library was used to extract the coordinate values of face feature points, collect the characteristic parameters of driver's eyes and mouth, and calculate the Euler Angle parameters of head posture. A fatigue identification model was constructed by using multiple characteristic parameters. (3) Genetic Algorithm (GA) was used to find the optimal smooth factor of Generalized Regression Neural Network (GRNN) and construct GA-GRNN fatigue driving identification model. Compared with K-Nearest Neighbor (KNN), Random Forest (RF), and GRNN fatigue driving identification algorithms. GA-GRNN has the best generalization ability and high stability, with an accuracy of 93.3%. This study provides theoretical and technical support for the application of driver fatigue identification.

The Effect of Pretreatment Potential Resistance to NNRTIs on Antiviral Therapy in Patients With HIV/AIDS.

BACKGROUND: With the increasing coverage of antiretroviral therapy, concerns for the emergence and transmission of HIV drug resistance (HIVDR) are arising. HIVDR was divided into 5 levels: sensitive, potentially resistant, low resistant, intermediate resistant, and high resistant. Most of the articles on HIVDR involved low-level, intermediate-level, and high-level drug resistance to antiretroviral drug, and few articles deal with potential drug resistance. Treatment failure associated with the level of low-level, intermediate-level, and high-level resistance to antiretroviral drug has been reported. However, whether virological failure (VF) is related to potential resistance remains unclear. In this study, we aimed to describe the situation of potential resistance to antiretroviral drug and whether it is related to VF. METHODS: We analyzed the demographic, behavioral information, medical history, and drug resistance-associated mutation data from subjects. Drug resistance mutations at baseline and time of failure in patients suffering VF were detected by using the Vela automated next-generation sequencing platform. The χ2 test or Fisher exact test and logistic regression were used to assess the risk factors that contribute to VF in the potential drug-resistant people. RESULTS: The prevalence of overall pretreatment drug resistance was 7.06% (233/3300), and the prevalence of pretreatment potential resistance was 8.79% (290/3300). All these patients with pretreatment potential first-line drugs resistance showed potential resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and some of them had potential drug resistance to NNRTIs and NRTIs or NNRTIs and PIs; among these patients, 94.71% (179/189) had V179 D/E mutations. The VF rate of first-line treatment for potentially resistant people is 17.99%. CD4+ T-cell count ≤200 cells/L at antiretroviral therapy initiation are risk factors for the failure of first-line treatment. CONCLUSIONS: The prevalence of potential drug resistance among individuals with HIV and the VF rate of first-line treatment for potential drug-resistant people were high. To better optimize clinical management, prevention, and control of HIV, attention should be devoted to the potential resistance of nonnucleoside drugs.

Assessment of Long-Term Effects on Pulmonary Functions Between Severe and Non-Severe Convalescent COVID-19 Patients: A Single-Center Study in China.

Objective: To explore the long-term effects of SARS-Cov-2 infection on the pulmonary function in the severe convalescent COVID-19 patients for 6 to 9 months follow-up in Beijing, China. Methods: A total of 64 cases of COVID-19 patients were recruited for the study and discharged from the Beijing Ditan Hospital, Capital Medical University, for 6 to 9 months. COVID-19 patients were divided into non-severe (mild and moderate) and severe groups. The follow-up investigated the lung function tests, the novel coronavirus antibody (IgM and IgG), chest CT and blood tests. Results: About 25.00% (16/64) patients had pulmonary ventilation dysfunction and 35.9% (23/64) had diffusion dysfunction. In the severe group, 56.50% (13/23) individuals showed decreased diffusion function. The diffusion dysfunction of the severe group was significantly decreased than the non-severe group (P = 0.01). Among 56 cases, the positive rate of IgG titers was 73.2% (41/56). The result of chest CT showed 55.36% (31/56) cases in nodules, 44.64% (25/56) in strip-like changes, 37.5% (21/56) in-ground glass shadow, and 5.36% (3/56) in grid shadow, which was significantly different between the severe group and the non-severe group. Patients tended to have ground glass changes in the severe group while nodules in the non-severe group. Conclusion: For the 6 to 9 months in convalescent COVID-19 patients, 56.50% (13/23) of severe patients had pulmonary diffusion dysfunction. Convalescent COVID-19 patients should have their pulmonary function regularly tested, especially those with severe illness.

Assessment of Clinical Features in HIV-Infected Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention in China.

Objectives: We aimed to compare coronary risk factors, burden of coronary artery disease (CAD), and 1-year prognosis of people living with HIV (PLWH) and HIV-negative controls who underwent percutaneous coronary intervention (PCI) for acute coronary syndromes (ACSs). Background: Cardiovascular disease is drawing more and more attention in PLWH since effective antiretroviral therapy (ART) has been available. Clinical characteristics and outcomes of PLWH undergoing PCI for ACS in China remain unknown. Methods: We compared demographic characteristics, angiographic features, and 1-year outcomes of 48 PLWH versus 48 HIV-negative controls matched for age (±2 years), sex, diabetes mellitus, and year of PCI (±2 years) in Beijing Ditan Hospital, Capital Medical University from January 2008 to November 2020. Results: In PLWH (mean age: 53.6 ± 10.6 years, 95.8% male, and 79.2% on ART), high-density lipoprotein cholesterol was lower than in HIV-negative controls; however, the statin use was more common, the incidence of hypertension was lower, and low-density lipoprotein cholesterol, and the body mass index were significantly lower than in controls. Two groups had a similar extent of coronary atherosclerosis as measured by the presence of multivessel diseases and the median Gensini score; however, lesions of PLWH were longer and were more likely to locate at the proximal segment of the coronary artery. In addition, the risk of major adverse cardiac and cerebrovascular events at 1 year was similar in both groups. Conclusion: PLWH undergoing PCI displayed similar CAD burden and 1-year prognosis compared with HIV-negative patients. Early detection of cardiovascular risk factors and appropriate secondary prevention of CAD in PLWH might alleviate the risk of severe adverse cardiovascular events.

A Real-Time Recognition System of Driving Propensity Based on AutoNavi Navigation Data.

Driving propensity is the driver's attitude towards the actual traffic situation and the corresponding decision-making or behavior during the driving process. It is of great significance to improve the accuracy of safety early warning and reduce traffic accidents. In this paper, a real-time identification system of driving propensity based on AutoNavi navigation data is proposed. The main work includes: (1) A dynamic data acquisition method of AutoNavi navigation is proposed to obtain the time, speed and acceleration of the driver during the navigation process. (2) The dynamic data collection method of AutoNavi navigation is analyzed and verified through the dynamic data obtained in the real vehicle experiment. The principal component analysis method is used to process the experimental data to extract the driving propensity characteristics variables. (3) The fruit fly optimization algorithm combined with GRNN (generalized neural network) and the feature variable set are used to build a FOA-GRNN-based model. The results show that the overall accuracy of the model can reach 94.17%. (4) A driving propensity identification system is constructed. The system has been verified through real vehicle test experiments. This paper provides a novel and convenient method for building personalized intelligent driver assistance systems in practical applications.

A Novel Prognostic Score Based on Artificial Intelligence in Hepatocellular Carcinoma: A Long-Term Follow-Up Analysis.

Objective: T cell immunity plays an important role in anti-tumor effects and immunosuppression often leads to the development and relapse of cancer. This study aimed to investigate the effect of T cell numbers on the long-term prognosis of patients with hepatocellular carcinoma (HCC) and construct an artificial neural network (ANN) model to evaluate its prognostic value. Methods: We enrolled 3,427 patients with HCC at Beijing Ditan Hospital, Capital Medical University, and randomly divided them into two groups of 1,861 and 809 patients as the training and validation sets, respectively. Cox regression analysis was used to screen for independent risk factors of survival in patients with HCC. These factors were used to build an ANN model using Python. Concordance index, calibration curve, and decision curve analysis were used to evaluate the model performance. Results: The 1-year, 3-year, 5-year, and 10-year cumulative overall survival (OS) rates were 66.9%, 45.7%, 34.9%, and 22.6%, respectively. Cox multivariate regression analysis showed that age, white blood cell count, creatinine, total bilirubin, γ-GGT, LDH, tumor size ≥ 5 cm, tumor number ≥ 2, portal vein tumor thrombus, and AFP ≥ 400 ng/ml were independent risk factors for long-term survival in HCC. Antiviral therapy, albumin, T cell, and CD8 T cell counts were independent protective factors. An ANN model was developed for long-term survival. The areas under the receiver operating characteristic (ROC) curve of 1-year, 3-year, and 5-year OS rates by ANNs were 0.838, 0.833, and 0.843, respectively, which were higher than those of the Barcelona Clinic Liver Cancer (BCLC), tumor node metastasis (TNM), Okuda, Chinese University Prognostic Index (CUPI), Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), and albumin-bilirubin (ALBI) models (P < 0.0001). According to the ANN model scores, all patients were divided into high-, middle-, and low-risk groups. Compared with low-risk patients, the hazard ratios of 5-year OS of the high-risk group were 8.11 (95% CI: 7.0-9.4) and 6.13 (95% CI: 4.28-8.79) (P<0.0001) in the training and validation sets, respectively. Conclusion: High levels of circulating T cells and CD8 + T cells in peripheral blood may benefit the long-term survival of patients with HCC. The ANN model has a good individual prediction performance, which can be used to assess the prognosis of HCC and lay the foundation for the implementation of precision treatment in the future.