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Abstract Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8+ T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8+ T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3β may regulate the INF-γ/PD-1 axis in CD8+ T cells from COVID-19 convalescent patients. In parallel, an IFN-γ neutralizing antibody reduced AKT and increased GSK3β in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3β. Moreover, AKT decreased PD-1 on CD8+ T cells, and GSK3β increased PD-1 on CD8+ T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8+ T cells by regulating the AKT/GSK3β signaling pathway.

To solve the problems of missing and false detection of pulmonary nodules in complex lung environments, as well as trivial and inefficient detection procedures, an end-to-end pulmonary nodules detection and recognition model based on deep learning was proposed. Innovation and improvement are made on the basis of YOLOv5. In the feature extraction stage of the model, a convolutional structure integrating self-attention mechanism is proposed to capture the global feature and the dependence relationship of long-distance information, and screen the key pathological information. Then, a convolution structure integrating internal convolution operators is proposed to reduce the computational redundancy in the feature channel and improve the inference speed of the model. In the feature fusion stage of the model, the structure of cross-scale coordinate attention feature fusion is proposed, and the different features enhanced with attention are weighted by jumping links to promote the fusion of multi-scale feature information. The proposed model obtained 97.8% mAP@0.5 indexes in the self-built diagnosis and treatment data set of pulmonary nodules in Huaihai area. The pulmonary nodule detection model proposed in this paper can significantly reduce the false positive rate and obtain the location and classification results of diseased nodules with higher detection accuracy and faster detection speed, which has important practical value in clinical application.

Abstract Background Antibiotic-resistant Klebsiella pneumoniae has emerged as a critical public health threat worldwide. Understanding the antimicrobial resistance mechanisms of multidrug-resistant K. pneumoniae (MDR-Kp) and its prevalence in time and space would provide clinical significance for managing pathogen infection. Methods Eighteen clinical MDR-Kp strains were analyzed by whole genome sequencing (WGS), and the antimicrobial resistance genes and associated resistance mechanisms were compared with results obtained from the conventional microbiological test (CMT). The sequence homology across strains in our study and those previously collected over time from a wide geographical region was assessed by phylogenetic analysis. Results MDR-Kp strains were collected from eighteen patients who had received empirical treatment before strain collection, with sputum (83.3%, 15/18) being the primary source of clinical samples. The commonly received treatments include β-lactamase inhibitors (55.6%, 10/18) and carbapenems (50%, 9/18). Using CMT, we found that all 18 strains were resistant to aztreonam and ciprofloxacin, while 14 (77.8%) showed resistance to carbapenem. Polymyxin B and tigecycline were the only antibiotics to which MDR-Kp strains were sensitive. A total of 42 antimicrobial resistance mechanisms were identified by WGS, surpassing the 40 detected by the conventional method, with 25 mechanisms shared between the two techniques. Despite a 100% accuracy rate of WGS in detecting penicillin-resistant strains, the accuracy in detecting cephalosporin-resistant strains was only at 60%. Among all resistance genes identified by WGS, Klebsiella pneumoniae carbapenemase-2 (KPC-2) was present in all 14 carbapenem-resistant strains. Phenotypic analysis indicated that sequence type (ST) 11 isolates were the primary cause of these MDR-Kp infections. Additionally, phylogenic clustering analysis, encompassing both the clinical and MDR-Kp strains previously reported in China, revealed four distinct subgroups. No significant difference was observed in the sequence homology between K. pneumoniae strains in our study and those previously collected in East China over time. Conclusion The application of WGS in identifying potential antimicrobial-resistant genes of MDR-Kp has demonstrated promising clinical significance. Comprehensive genomic information revealed by WGS holds the promise of guiding treatment decisions, enabling surveillance, and serving as a crucial asset in understanding antibiotic resistance.

BackgroundObesity is a prevalent health problem in patients with schizophrenia, and calorie restriction diet (CRD) achieved effective weight loss and metabolic improvement; however, these have not been rigorously evaluated in obese patients with schizophrenia.ObjectiveTo measure the effects of CRD on weight loss and metabolic status in hospitalized obese women with schizophrenia during a 4-week period.MethodsParticipants were randomly assigned to two groups in a 1:1 ratio. The intervention group (n = 47) was asked to follow a CRD and the control group (n = 48) a normal diet for 4 weeks. Outcomes of body weight, body composition, as well as metabolic parameters were measured at baseline and following the intervention period.ResultsForty-five participants completed the 4-week research in both the intervention and control groups. Compared to the normal diet, adherence to the CRD significantly decreased body weight (2.38 ± 1.30 kg), body mass index (0.94 ± 0.52 kg/m2), waist circumference (4.34 ± 2.75 cm), hip circumference (3.37 ± 2.36 cm), mid-upper circumferences, triceps skin-fold thickness, fat mass and free fat mass with large effect sizes (p = 0.05).ConclusionCRD is preventative of weight gain, but not apparent in intervention for metabolic status in hospitalized obese women with schizophrenia.Clinical trial registration: http://www.chictr.org.cn, ChiCTR-INR-16009185.

Due to the shallow burial of groundwater in coal mines with a high phreatic water level, a large area of subsidence lakes is formed after the mine collapses. Agricultural and fishery reclamation activities have been carried out, which introduced antibiotics and exacerbated the contamination of antibiotic resistance genes (ARGs), but this has received limited attention. This study analyzed ARG occurrence in reclaimed mining areas, the key impact factors, and the underlying mechanism. The results show that sulfur is the most critical factor impacting the abundance of ARGs in reclaimed soil, which is due to changes in the microbial community. The species and abundance of ARGs in the reclaimed soil were higher than those in the controlled soil. The relative abundances of most ARGs increased with the depth of reclaimed soil (from 0 to 80 cm). In addition, the microbial structures of the reclaimed and controlled soils were significantly different. Proteobacteria, was the most dominant microbial phylum in the reclaimed soil. This difference is likely related to the high abundance of sulfur metabolism functional genes in the reclaimed soil. Correlation analysis showed that the differences in ARGs and microorganisms in the two soil types were highly correlated with the sulfur content. High levels of sulfur promoted the proliferation of sulfur-metabolizing microbial populations such as Proteobacteria and Gemmatimonadetes in the reclaimed soils. Remarkably, these microbial phyla were the main antibiotic-resistant bacteria in this study, and their proliferation created conditions for the enrichment of ARGs. Overall, this study underscores the risk of the abundance and spread of ARGs driven by high-level sulfur in reclaimed soils and reveals the mechanisms.

Escherichia coli (E. coli) is a common opportunistic pathogen for nosocomial infection. The aim of the study was to examine the phenotype, genotype and epidemiology of plasmid-mediated AmpC β-lactamases in E. coli. In total, 96 clinical isolates of repeated E. coli were collected from different hospitals between August and October 2012. Using a cefoxitin disk diffusion method to identify the phenotype of AmpC β-lactamases in E. coli, the plasmid was extracted, and multiplex polymerase chain reaction (PCR) was used to determine the amp gene. The PCR products were purified and sequenced. Of the 96 isolates strains, 43 strains were cefoxitin-resistant. Twelve (12.5%) isolates were detected to produce AmpC β-lactamases with multiplex PCR, 11 strains carried DHA type ampC-resistant genes, and one strain carried ACC type ampC-resistant genes. In conclusion, the incidence of producing a plasmid-mediated AmpC enzyme of E. coli strains was relatively high. Therefore, antibiotics such as imipenem, a carbapenem, potentially serve as the treatment of choice for the infection. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the prevalence and related drug resistance of AmpC β-lactamases in Acinetobacter baumannii in tertiary-level hospitals in the Xuzhou region in China. A total of 134 clinical isolates of non-repetitive Acinetobacter baumannii were collected from different hospitals in the Xuzhou region, and multiplex polymerase chain reaction (PCR) was employed to determine the genotype of AmpC. The PCR products were purified and sequenced. The susceptibility to antibiotics was tested using the biometrics automated microbiological-assay system, VITEK-2. Amongst the 134 isolated strains, 96 strains were found to produce AmpC β-lactamases, and the positive rate was 72%, all of which carried acinetobacter-derived cephalosporinase (ADC) type AmpC resistance genes. The drug sensitivity tests indicated that the positive Acinetobacter baumannii strains were resistant to the majority of extended-spectrum β-lactam antibiotics, but were only sensitive to polymyxin. In conclusion, the incidence of AmpC enzymes in Acinetobacter baumannii strains in tertiary-level hospitals in the Xuzhou area is relatively high, and resistance to the majority of extendedspectrum β-lactam antibiotics may be related to the ADC type of AmpC. [ABSTRACT FROM AUTHOR]

[Objective] To observe the effects of baicalin on the NF-κB and ACF2 protein expression in atherosclerosis of ApoE-/-mice induced by hyperlipaemia, and to discuss the possible mechanism of baicalin in interfering the atherosclerosis process. [Methods] 30 healthy apoE-/-mice at 6 weeks old were randomly divided into model group and baicalin groups; and 10 wild C57BL mice were taken as the normal control group. Mice in control group were given normal feed. Mice in model group and baicalin groups were given high fat diet for 12 weeks. AS model was established. Mice in baicalin groups were given 3(X) and 150 mg/d baicalin by gavage for continuous 8 weeks. After 20 weeks, mice were killed. The blood lipid was detected; immunohistochemical analysis of the expression levels of NF-κB and ACE2 were carried out. [Results] Grey value of NF-κB in aortic wall cells of apoF-/-mice in baicalin group was significantly higher than that in model group; and the grey value of ACE2 reduced, showing statistical significance (P <0.05). [Conclusions] Baicalin might intervene in the development of atherosclerosis through restricting transcriptional expression of NF-κB. affecting the inflammatory reaction and enliancing the ACE2 protein expression. [ABSTRACT FROM AUTHOR]