Search

Background: Ischemia/reperfusion (I/R) is an inevitable pathophysiological process during heart transplantation, and ferroptosis is an important pathogenic mechanism. Unlike other modes of cell death, ferroptosis depends on the accumulation of iron within the cell and the oxidative degradation of polyunsaturated fatty acids. Dysregulation of this pathway has been linked to the progression of multiple pathological conditions, making it an attractive target for therapeutic intervention. Therefore, this study aims to explore the effect of ferroptosis on I/R during heart transplantation., Methods: GEO2R was applied to identify differentially expressed genes (DEGs) obtained from GSE50884 data, which was involved in I/R and heart transplantation. And ferroptosis-related DEGs (FRDEGs) were screened by venn diagram with ferroptosis-related genes downloaded from FerDb database. FRDEGs was enriched and analyzed by GO and KEGG, and hub genes related to ferroptosis were screened by Cytoscape software and database STRING. Additionally, considering the relationship between ferroptosis and immunity, CIBERSORTx was to analyze the infiltration of 22 kinds of immune cells in I/R during heart transplantation, and the correlation between each immune cell and the expression of FRDEGs was also discussed. Finally, the mouse model of heart transplantation with I/R was constructed, and the hub genes was verified by RT-qPCR and western blot., Results: 12 FRDEGs were identified out of 327 DEGs in GSE50844, which were mainly involved in ferroptosis and other pathways. Three hub genes (SLC7A11, PSAT1, ASNS) were obtained by the degree algorithm of cytohubba plug-in. Immunoinfiltration analysis showed that 16 of 22 immune cells changed, and the immune score of heart transplantation with I/R was higher than that without I/R. In addition, hub genes exhibited significant correlation with Eosinophils, NK cells resting, Dendritic cells resting, NK cells activated and T cells CD4 memory activated. We verified the expression of SLC7A11, PSAT1 and ASNS was higher than that in normal tissues using RT-qPCR and western blot in mouse models of heart transplantation with I/R, companied by ferroptosis aggravated is involved., Conclusions: In short, ferroptosis is involved in I/R injury during heart transplantation, which is related to immune cell infiltration. Three hub genes (SLC7A11, PSAT1 and ASNS) identified in this study provide therapeutic targets for ameliorating I/R injury in heart transplantation., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Ethics Committee of Renmin Hospital of Wuhan University and were conducted in accordance with the regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) is associated with high mortality, heavy economic burden, limited treatment options and poor prognosis, and seriously affects the health-related quality of life (HRQoL) and life expectancy of patients. This systematic review and meta-analysis of HRQoL and health state utility value (HSUV) in IPF patients and the instruments used in this assessment aimed to provide information sources and data support for the future research on IPF HRQoL and HSUV., Methods: We searched the PubMed, EMBASE, Web of Science and Cochrane Library databases for studies reporting the HRQoL or HSUV of IPF patients, with the retrieval time from the establishment of each database to April 2024. After two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies, pooled analysis was performed on the measurement tools adopted in more than two studies. Subgroup analysis was employed to explore the source of heterogeneity, and sensitivity analysis was used to assess the robustness of the results. Funnel-plot directed evaluation combined with Egger's test quantitative evaluation was conducted to detect publication bias., Results: Sixty-nine studies were ultimately included, covering eighteen measurement tools. The literature quality was generally excellent. The St. George's Respiratory Questionnaire (SGRQ), EuroQoL Five Dimensions Questionnaire (EQ-5D), Short Form-36 (SF-36) and the King's Brief Interstitial Lung Disease (KBILD) were the most common instruments, among which the EQ-5D included the HSUV and the visual analog scale (VAS). The results of the meta-analysis revealed that the pooled SGRQ total score was 45.28 (95% confidence interval [CI] 41.10-49.47), the mean EQ-5D utility score was 0.75 (95% CI: 0.72-0.79), the total EQ-5D VAS score was 66.88 (95% CI: 63.75-70.01), and the pooled SF-36 physical component summary (PCS) and mental component summary (MCS) score were 36.70 (95% CI: 32.98-40.41) and 48.99 (95% CI: 47.44-50.55), respectively. The total KBILD score was 58.31 (95% CI: 55.43-61.19), the IPF specific version of the SGRQ (SGRQ-I) was 40.38 (95% CI: 28.81-51.96) and the Leicester Cough Questionnaire (LCQ) score was 16.09 (95% CI: 15.45-16.74). The pooled result of the University of California San Diego Shortness of Breath Questionnaire (USCD-SOBQ) was 45.05 (95% CI: 41.56-48.55). The results of other instruments, such as the tool to assess quality of life in IPF (ATAQ-IPF), the World Health Organization Quality of Life assessment 100 (WHOQoL-100) and the 12-item short-form health survey (SF-12) were similar to those of the above measurement tools. Regretfully, subgroup analyses did not identify the source of heterogeneity, but sensitivity analyses demonstrated robustness of our results. Except for the SGRQ total, our results showed little possibility of publication bias., Conclusions: HRQoL in IPF patients is generally poor, and all domains are severely affected. With the aggravation of disease, HRQoL and HSUV shows a relatively downward trend, and income level is also an important factor affecting HRQoL and HSUV. At present, the published studies on IPF HRQoL and HSUV have applied many measurement tools with high interstudy heterogeneity, and future research on the optimal disease measurement tools should be strengthened. Our study provides high-quality comprehensive evidence for IPF HRQoL and HSUV, which can be used to guide clinical and economic evaluation in the future., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purposes: The objective of this study was to investigate intra-articular distal radius fractures, aiming to provide a comprehensive analysis of fracture patterns and discuss the corresponding treatment strategies for each pattern., Methods: 294 cases of intra-articular distal radius fractures lines were collected and clustered thorough K-means and hierarchical clustering algorithm. The demographic data of patients and the clinical treatment outcomes were recorded. For functional evaluation, quick Disabilities of the Arm, Shoulder, and Hand (DASH) score, visual analog scale (VAS) pain score, range of motion (ROM) of the wrist joint and the percentage of the grip strength relative to the healthy wrist at 12 months follow-up were evaluated and recorded; For radiographic parameters of volar tilt (VT), radial inclination (RI), and ulnar variance (UV) were obtained; The occurrence of complications was carefully assessed and documented., Results: Totally 294 patients were included and divided into the volar side affected group and the dorsal side affected groups. And each group was further categorized into three types: type I, with two parts fractures with either one volar/dorsal side intact; type II, with three parts fractures with  volar/dorsal side simply affected; and type III, with four parts fractures with volar/dorsal side communited affected. The volar plate fixation was performed as the standard treatment, while the combined plate fixation was used for comminuted dorsal bone defects of the metaphysis and impaction. There were no differences in the postoperative radiograph parameters, functional outcomes and incidences of complications for each type of volar side group and dorsal side group except that the 3.2 type DRFs showed less range of flexion (75.56±7.48)° and extension (61.65±9.9)° than other dorsal types., Conclusions: A new intra-articular distal radius fractures classification was proposed based on the affection condition of volar or dorsal side. The volar plate fixation is an effective treatment for the intra-articular distal radius fractures, while combined plate fixation can be considered as an alternative treatment for dorsal side comminuted fractures., Level of Evidence: III a., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Chaoyang Hospital, Capital Medical University in accordance with the Declaration of Helsinki.(Clinical trial number :2021-科-441;Registration Date: 2021/7/5) Informed consent to participate was obtained from all of the participants in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The modification of protein substrates by small ubiquitin-related modifier (SUMO) plays a vital role in plants subjected to biotic and abiotic stresses. However, its role in the stress responses of Brassica plants remains poorly understood., Results: A genome-wide analysis revealed the presence of 30 SUMOylation genes in the Caixin genome. These results demonstrated that the Caixin genome contains all the necessary components for SUMOylation. Analysis of the cis-acting elements revealed that the promoters of SUMOylation genes presented diverse combinations of developmental and stress-related cis-regulatory elements. The RNA-seq data indicated that 23 SUMOylation genes presented relatively high expression levels under normal conditions and exhibited a notable decrease in expression following Pectobacterium carotovorum subsp. carotovorum (Pcc) infection. Additionally, dynamic alterations in SUMO conjugates were observed in response to Pcc infection., Conclusions: The Caixin genome contains genes involved in SUMOylation. The majority of these genes presented multiple copies, and analyses of their transcription and protein profiles indicate that they may play a role in the response to Pcc infection., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Premature ovarian insufficiency (POI) is a common clinical problem, but there is currently no effective treatment. NLRP3 inflammasome-induced pyroptosis is thought to be a possible mechanism of POI. Nicotinamide mononucleotide (NMN) has a certain anti-inflammatory effect, providing a promising approach for the treatment of POI., Methods: Thirty female Sprague Dawley rats were randomly divided into a control group (n = 10) and a POI group (n = 20). Cyclophosphamide (CTX) was administered for 2 weeks to induce POI. Then the POI group was divided into two groups: the CTX-POI group (n = 10), which was given saline; and the CTX-POI + NMN group (n = 10), which was given NMN at a dose of 500 mg/kg/day for 21 consecutive days. At the end of the study, the serum hormone concentrations of each group were determined, and each group was subjected to biochemical, histopathological, and immunohistochemical analyses. In the in vitro experiment, cell pyroptosis was simulated by using lipopolysaccharide (LPS) and nigricin (Nig), and then KGN cells were treated with NMN, MCC950, and AGK2, and the levels of Nicotinamide adenine dinucleotide (NAD + ) and inflammatory factors Interleukin-18(IL-18) and Interleukin-1β(IL-1β) in the cell supernatants were detected, and the levels of pyroptosis-related factors in the cells were determined., Results: In POI rats, NMN treatments can improve blood hormone levels and partially improve the number of follicles, enhance ovarian reserve function and ovarian index.The evidence is that the increase in NAD + levels and the activation of SIRT2 expression can reduce the expression of NLRP3, Gasdermin D (GSDMD), Caspase-1, IL-18, and IL-1β in the ovary., Conclusion: NMN improves CTX-induced POI by inhibiting NLRP3-mediated pyroptosis, providing a new therapeutic strategy and drug target for clinical POI patients., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Experimental Animal Welfare Ethics Review Committee of South China University of Technology. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number. Not applicable., (© 2024. The Author(s).)

Background: Selective RET inhibitors have been approved by the Chinese government for the treatment of RET-rearranged non-small cell lung cancer. This study aimed to illustrate the efficacy and safety of selective RET inhibitors in a real-world clinical context in China., Methods: Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring RET rearrangement and receiving RET tyrosine kinase inhibitors (RET-TKI) in the real world were enrolled in this retrospective study. Clinical data, including baseline clinicopathological information, efficacy parameters such as objective response rate (ORR) and progression-free survival (PFS), and adverse events (AEs), were collected from the electronic medical record system. The pattern of treatment failure of first-line RET-TKI was also described., Results: Fifty-one patients were enrolled in this study. RET-TKI induced an ORR of 73.1% and a median PFS (mPFS) of 22.7 months (95%CI, 11.7-33.7) in the first-line setting. The ORR and mPFS were 58.3% and 17.7 months (95%CI, 9.1-26.2), 55.6% and 14.7 months (95%CI, 12.6-16.8) in the second-line and later-line settings, respectively. No significant difference was observed among different application lines with respect to the ORR (P = 0.534) or PFS (P = 0.795). In the first-line setting, RET-TKI significantly prolonged PFS compared to other regimens including chemotherapy-based regimens, multikinase inhibitors and other systemic regimens without chemotherapy (P < 0.05). Poor ECOG performance status was related to shorter PFS (P = 0.018). The most common AEs of grade 3 or worse were a decreased neutrophil count (11.4%) and anemia (11.4%). No new AEs or grade 5 AEs were observed. Brain metastasis was one of the most common patterns of treatment failure. In patients with baseline brain metastasis, the intracranial ORR was 50%, and the DCR was 100%., Conclusions: RET-TKI had favorable efficacy and safety in real-world contexts in China and should be considered the preferred choice for first-line treatment in RET-rearranged NSCLC patients., Competing Interests: Declarations Ethics approval and consent to participate The Ethics Committee of National Cancer Center/ Cancer Hospital/ Chinese Academy of Medical Sciences and Peking Union Medical College approved the study and waived the informed consent for its retrospective noninvasive nature (Approval Number: 18–070/1648). Consent for publication All authors have agreed the publication of this study. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Mandibular retraction is a prevalent dental and maxillofacial deformity that negatively affects patients' functional health and facial aesthetics. It has been challenging to achieve optimal outcomes for patients who have passed the peak of growth and development using only functional orthopedic treatment. There is a pressing need to explore innovative methods to promote the adaptive remodeling of adult condylar cartilage and the mandible in response to external stimuli. This study aimed to investigate the impact of varying injection frequencies of stem cells from the apical papilla (SCAPs) on the growth and development of condylar cartilage and the mandible, as well as their potential for adaptive remodeling., Methods: The study was conducted on 8-week-old adult male Sprague-Dawley rats. The effects of SCAPs injection and different durations of mandibular advancement (MA) on the adaptive remodeling of condylar cartilage and the mandible were assessed. After the initial experimental findings, various injection frequencies of SCAPs were applied to determine the most effective conditions for promoting the growth and adaptive remodeling of condylar cartilage and the mandible during an 8-week period of mandibular advancement., Results: The study found that rats with extended mandibular lead times (8 weeks) or an appropriately increased frequency of mandibular leading time (once every 2 weeks or once every 1 week) exhibited increased lengths of the mandibular body and ascending branch, and a thickened full layer of condylar cartilage. The highest proportions of the proliferative layer, mature layer, and hypertrophic layer were observed in these rats. Additionally, there was a significant increase in the expression levels of SOX9 and COL2A1., Conclusion: The data from this study suggest that adult rats, even after missing their peak growth period, retain the potential for continued growth and development of their condylar cartilage. By prolonging the duration of mandibular advancement and administering injections of stem cells from the apical papilla (SCAPs), it is possible to stimulate the growth and development of the mandibular condyle., Competing Interests: Declarations Ethics approval and consent to participate All human cell cultures and animal experiments conducted in this study were approved by the Ethics Committees of the Jinan University (No. JNUKY-2023–0110). The approved project was titled “Construction and orthodontic function evaluation of 3D Printed Autologous Tooth-Bone transformation prosthesis based on CEMP1 regulating periodontal regeneration mechanism.” The date of approvals is December 29, 2023. Written informed consents were obtained from patients and their families who provided teeth for further research. Consent for publication Not applicable. Competing interests The authors have declared no competing interests., (© 2024. The Author(s).)

Purpose: A growing body of research indicates a correlation between occupational exposure, particularly among individuals in driving-related occupations, and the incidence of low back pain (LBP)., Methods: Databases were systematically searched, including PubMed, Embase, Web of Science, Cochrane Library, and SinoMed, from their inception through December 2023 for relevant studies of the prevalence and risk factors of LBP among professional drivers. Subsequent meta-analyses were performed utilizing Stata 17.0 and RevMan 5.4 software, while risk factor indicators were assessed using the Grading of Recommendations, Assessment, Development and Evaluation evidence quality grading system., Results: A systematic review and meta-analysis comprising 19 studies involving 7,723 patients indicated that the incidence of LBP among drivers was 39% (95% confidence interval [CI] 0.20-0.57) in the past 7 days and 53% (95% CI 0.43-0.63) in the past 12 months. A subgroup analysis revealed a prevalence of 48% (95% CI 0.33-0.64) in 2005-2015 and 56% (95% CI 0.42-0.70) in 2016-2023. Among the identified factors, robust evidence highlighted age ≥ 41 years (odds ratio [OR] = 2.10; 95% CI 1.36-3.24; P = 0.0008), alcohol consumption (OR = 1.75; 95% CI 1.31-2.34; P = 0.0001), sleeping < 6 h/night (OR = 1.60; 95% CI 1.13-2.24; P = 0.007), uncomfortable seating (OR = 1.71; 95% CI 1.23-2.36; P = 0.001), improper driving posture (OR = 2.37; 95% CI 1.91-2.94; P < 0.00001), and manual handling (OR = 2.23; 95% CI 1.72-2.88; P < 0.00001) as significant risk factors for LBP. There was moderate evidence of a lack of exercise (OR = 1.78; 95% CI 1.37-2.31; P < 0.0001), working > 10 h/day (OR = 2.49; 95% CI 1.89-3.28; P < 0.00001), > 5 years' driving experience (OR = 2.12; 95% CI 1.66-2.69; P < 0.00001), a lack of back support (OR = 1.81; 95% CI 1.25-2.62; P = 0.002), high work-related pressure (OR = 2.04; 95% CI 1.59-2.61; P < 0.00001), and job dissatisfaction (OR = 1.57; 95% CI 1.23-2.01; P = 0.0003) as moderate risk factors. There was no evidence of body mass index or smoking as risk factors for LBP among professional drivers., Conclusion: The current evidence indicates an increasing annual trend in the prevalence of LBP among professional drivers. Factors including age ≥ 41 years, alcohol consumption, and sleeping < 6 h/night were among the 12 influential factors contributing to LBP in professional drivers. Enhancing awareness of these factors and formulating targeted preventive strategies may be beneficial., (© 2024. The Author(s).)

Background: Periodontitis is the sixth-most common disease worldwide. The oral microbiome composition and its association with Periodontal disease (PD) have been largely explored; however, limited studies have explored the microbial profiles of both oral and toothbrushes in patients with PD. Thus, this study aimed to ascertain the oral and toothbrushes microbial composition in high-altitude populations, hypothesizing that their correlation with periodontal health would differ from those at lower altitudes, potentially indicating links between environmental factors, microbial colonization patterns, and periodontal health in distinct geographic contexts., Methods: In the present study, we enrolled 35 individuals including 21 healthy and 14 diagnosed with PD from the Lhasa region of Tibet, China. Saliva and toothbrush samples were collected from each participant to assess the association between toothbrush usage and oral microbiome with PD using 16 S rRNA gene-specific V3-V4 regions sequencing. To assess the oral and toothbrush microbiome composition and diversity and its possible link to PD., Results: Significantly higher Alpha diversity (Shannon index) was observed between the PD group and PD toothbrushes (p = 0.00021) and between the PD group and Healthy toothbrushes (p = 0.00041). The predominant species were Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Fusobacteria, with genera Pseudomonas, Veillonella, Neisseria, Acinetobacter, and Haemophilus. In addition, PICRUST2 analysis unveiled 44 significant pathways differentiating the disease and healthy groups, along with 29 pathways showing significant differences between their respective toothbrush microbial profiles. The distinct oral and toothbrush microbial composition among high-altitude populations suggests potential adaptations to the challenges of high-altitude environments., Conclusion: This study emphasizes the importance of tailored dental care strategies, accounting for altitude and racial factors, to effectively manage periodontal health in these communities. Further research is warranted to investigate the specific microbial mechanisms and develop targeted interventions for optimizing oral health in populations across varying altitudes., (© 2024. The Author(s).)

Background: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method., Methods: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method., Results: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes., Conclusion: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories., (© 2024. The Author(s).)

Background: With the accumulating omics data, an efficient and time-saving transient assay to express target genes is desired. Mesophyll protoplasts, maintaining most stress-physiological responses and cellular activities as intact plants, offer an alternative transient assay to study target genes' effects on heat and oxidative stress responses., Results: In this study, a perennial ryegrass (Lolium perenne L.) mesophyll protoplast-based assay was established to effectively over- or down-regulate target genes. The relative expression levels of the target genes could be quantified using RT-qPCR, and the effects of heat and H 2 O 2 -induced oxidative stress on protoplasts' viability could be quantitatively measured. The practicality of the assay was demonstrated by identifying the potential thermos-sensor genes LpTT3.1/LpTT3.2 in ryegrass that over-expressing these genes significantly altered protoplasts' viability rates after heat stress., Conclusion: This protoplast-based rapid stress regulatory gene identification assay was briefed as 'PRIDA' that will complement the stable genetic transformation studies to rapidly identify candidate stress-regulatory genes in perennial ryegrass and other grass species., (© 2024. The Author(s).)

Background: Ischemic postconditioning (IPostC) has been reported as a promising method for protecting against myocardial ischemia-reperfusion (MI/R) injury. Our previous study found that the infarct-limiting effect of IPostC is abolished in the heart of diabetes whose cardiac expression of DJ-1 (also called PARK7, Parkinsonism associated deglycase) is reduced. However, the role and in particular the underlying mechanism of DJ-1 in the loss of sensitivity to IPostC-induced cardioprotection in diabetic hearts remains unclear., Methods: Streptozotocin-induced type 1 diabetic rats were subjected to MI/R injury by occluding the left anterior descending artery (LAD) and followed by reperfusion. IPostC was induced by three cycles of 10s of reperfusion and ischemia at the onset of reperfusion. AAV9-CMV-DJ-1, AAV9-CMV-C106S-DJ-1 or AAV9-DJ-1 siRNA were injected via tail vein to either over-express or knock-down DJ-1 three weeks before inducing MI/R., Results: Diabetic rats subjected to MI/R exhibited larger infarct area, more severe oxidative injury concomitant with significantly reduced cardiac DJ-1 expression and increased PTEN expression as compared to non-diabetic rats. AAV9-mediated cardiac DJ-1 overexpression, but not the cardiac overexpression of DJ-1 mutant C106S, restored IPostC-induced cardioprotection and this effect was accompanied by increased cytoplasmic DJ-1 translocation toward nuclear and mitochondrial, reduced PTEN expression, and increased Nrf-2/HO-1 transcription. Our further study showed that AAV9-mediated targeted DJ-1 gene knockdown aggravated MI/R injury in diabetic hearts, and this exacerbation of MI/R injury was partially reversed by IPostC in the presence of PTEN inhibition or Nrf-2 activation., Conclusions: These findings suggest that DJ-1 preserves the cardioprotective effect of IPostC against MI/R injury in diabetic rats through nuclear and mitochondrial DJ-1 translocation and that inhibition of cardiac PTEN and activation of Nrf-2/HO-1 may represent the major downstream mechanisms whereby DJ-1 preserves the cardioprotective effect of IPostC in diabetes., (© 2024. The Author(s).)

Background: B-box (BBX) proteins are a type of zinc finger proteins containing one or two B-box domains. They play important roles in development and diverse stress responses of plants, yet their roles in wheat remain unclear., Results: In this study, 96 BBX genes were identified in the wheat genome and classified into five subfamilies. Subcellular localization prediction results showed that 68 TaBBXs were localized in the nucleus. Protein interaction prediction analysis indicated that interaction was one way that these proteins exerted their functions. Promoter analysis indicated that TaBBXs may play important roles in light signal, hormone, and stress responses. qRT-PCR analysis revealed that 14 TaBBXs were highly expressed in seeds compared with other tissues. These were probably involved in seed dormancy and germination, and their expression patterns were investigated during dormancy acquisition and release in the seeds of wheat varieties Jing 411 and Hongmangchun 21, showing significant differences in seed dormancy and germination phenotypes. Subcellular localization analysis confirmed that the three candidates TaBBX2-2 A, TaBBX4-2 A, and TaBBX11-2D were nuclear proteins. Transcriptional self-activation experiments further demonstrated that TaBBX4-2A was transcriptionally active, but TaBBX2-2A and TaBBX11-2D were not. Protein interaction analysis revealed that TaBBX2-2A, TaBBX4-2A, and TaBBX11-2D had no interaction with each other, while TaBBX2-2A and TaBBX11-2D interacted with each other, indicating that TaBBX4-2A may regulate seed dormancy and germination by transcriptional regulation, and TaBBX2-2A and TaBBX11-2D may regulate seed dormancy and germination by forming a homologous complex., Conclusions: In this study, the wheat BBX gene family was identified and characterized at the genomic level by bioinformatics analysis. These observations provide a theoretical basis for future studies on the functions of BBXs in wheat and other species., (© 2024. The Author(s).)

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis., (© 2024. The Author(s).)

Background: Chylous leakage is a rare complication following esophagectomy; however, it can lead to mortality. We aimed to systematically evaluate the factors that may lead to increased chylous leakage after esophagectomy., Methods: Three databases (PubMed, Embase, and Cochrane Library) were systematically searched for all studies investigating the occurrence of chylous leakage after esophagectomy., Results: A total of 32 studies were identified, including 26 randomized controlled trials and 3 cohort and case-control studies, each. The overall incidence of chylous leakage was 4.7% (278/5,971 cases). Analysis of preoperative, intraoperative, and postoperative factors showed that most of the qualitative analysis results did not significantly increase the incidence of chylous leakage. In some quantitative analyses, the chylous leakage rate was significantly lower in the thoracic duct mass ligation group than in the conservative treatment group (relative risk [RR] = 0.33; 95% confidence interval [CI], 0.13-0.83; I 2  = 0.0%; P = 0.327). Direct oral feeding significantly reduced chylous leakage compared with jejunostomy (RR = 0.06; 95% CI 0.01-0.33; I 2  = 0.0%; P = 0.335). However, preoperative inspiratory muscle training (RR = 1.66; 95% CI, 0.21-12.33; I 2  = 55.5%; P = 0.134), preoperative chemoradiotherapy (RR = 0.99; 95% CI, 0.55-1.80; I 2  = 0.0%; P = 0.943), and robotic assistance (RR = 1.62; 95% CI, 0.92-2.86; I 2  = 0.0%; P = 0.814) did not significantly reduce the incidence of chylous leakage., Conclusions: Ligation of the thoracic duct and direct oral feeding can reduce the incidence of chylous leakage after esophagectomy in patients with esophageal cancer. Other contributing factors remain unclear and require validation in further high-quality studies., (© 2024. The Author(s).)

Background: Calcium-dependent protein kinases (CPKs) are crucial for recognizing and transmitting Ca 2+ signals in plant cells, playing a vital role in growth, development, and stress response. This study aimed to identify and detect the potential roles of the CPK gene family in the amphidiploid Brassica carinata (BBCC, 2n = 34) using bioinformatics methods., Results: Based on the published genomic information of B. carinata, a total of 123 CPK genes were identified, comprising 70 CPK genes on the B subgenome and 53 on the C subgenome. To further investigate the homologous evolutionary relationship between B. carinata and other plants, the phylogenetic tree was constructed using CPKs in B. carinata and Arabidopsis thaliana. The phylogenetic analysis classified 123 family members into four subfamilies, where gene members within the same subfamily exhibited similar conserved motifs. Each BcaCPK member possesses a core protein kinase domain and four EF-hand domains. Most of the BcaCPK genes contain 5 to 8 introns, and these 123 BcaCPK genes are unevenly distributed across 17 chromosomes. Among these BcaCPK genes, 120 replicated gene pairs were found, whereas only 8 genes were tandem duplication, suggesting that dispersed duplication mainly drove the family amplification. The results of the Ka/Ks analysis indicated that the CPK gene family of B. carinata was primarily underwent purification selection in evolutionary selection. The promoter region of most BcaCPK genes contained various stress-related cis-acting elements. qRT-PCR analysis of 12 selected CPK genes conducted under cadmium and salt stress at various points revealed distinct expression patterns among different family members in response to different stresses. Specifically, the expression levels of BcaCPK2.B01a, BcaCPK16.B02b, and BcaCPK26.B02 were down-regulated under both stresses, whereas the expression levels of other members were significantly up-regulated under at least one stress., Conclusion: This study systematically identified the BcaCPK gene family in B. carinata, which contributes to a better understanding the CPK genes in this species. The findings also serve as a reference for analyzing stress responses, particularly in relation to cadmium and salt stress in B. carinata., (© 2024. The Author(s).)

Background: Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies., Methods: The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients., Conclusions: The MOYAOMICS project represents a significant step toward comprehending MMD's molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease., (© 2024. The Author(s).)

Background: Ribosomal protein SA (RPSA) of human brain microvascular endothelial cells (HBMECs) can transfer from the cytosol to the cell surface and act as a receptor for some pathogens, including Streptococcus suis serotype 2 (SS2), a zoonotic pathogen causing meningitis in pigs and humans. We previously reported that SS2 virulence factor enolase (ENO) binds to RPSA on the cell surface of HBMECs and induces apoptosis. However, the mechanism that activates RPSA translocation to the cell surface and induces ENO-mediated HBMEC apoptosis is unclear., Results: Here, we show that RPSA localization and condensation on the host cell surface depend on its internally disordered region (IDR). ENO binds to the IDR of RPSA and promotes its interaction with RPSA and vimentin (VIM), which is significantly suppressed after 1,6-Hexanediol (1,6-Hex, a widely used tool to disrupt phase separation) treatment, indicating that ENO incorporation and thus the concentration of RPSA/VIM complexes via co-condensation. Furthermore, increasing intracellular calcium ions (Ca 2+ ) in response to SS2 infection further facilitates the liquid-like condensation of RPSA and aggravates ENO-induced HBMEC cell apoptosis., Conclusions: Together, our study provides a previously underappreciated molecular mechanism illuminating that ENO-induced RPSA condensation activates the migration of RPSA to the bacterial cell surface and stimulates SS2-infected HBMEC death and, potentially, disease progression. This study offers a fresh avenue for investigation into the mechanism by which other harmful bacteria infect hosts via cell surfaces' RPSA., (© 2024. The Author(s).)

Objective: To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC)., Methods: This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model., Results: The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74-27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27-18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM., Conclusion: Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists., (© 2024. The Author(s).)

Background: To study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection., Methods: The clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared., Results: The effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2-37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931., Conclusions: Rational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI., (© 2023. The Author(s).)

Background: Histones posttranslational modification represent an epigenetic mechanism that regulate gene expression and other cellular processes. Quantitative mass spectrometry used for the absolute quantification of such modifications provides further insight into cellular responses to extracellular insults such as infections or toxins. Methamphetamine (Meth), a drug of abuse, is affecting the overall function of the immune system. In this report, we developed, validated and applied a targeted, MS-based quantification assay to measure changes in histone H3 lysine 14 acetylation (H3K14Ac) during exposure of human primary macrophages to HIV-1 infection and/or Meth., Methods: The quantification assay was developed and validated to determine H3K14Ac stoichiometry in histones that were isolated from the nuclei of control (CIC) and exposed to Meth before (CIM) or/and after (MIM) HIV-infection human monocyte-derived macrophages (hMDM) of six donors. It was based on LC-MS/MS measurement using multiple reaction monitoring (MRM) acquisition of the unmodified and acetylated form of lysine K14 of histone H3 9 KSTGGKAPR 17 peptides and the corresponding stable isotope labeled (SIL) heavy peptide standards of the same sequences. The histone samples were propionylated (Poy) pre- and post- trypsin digestion so that the sequences of the monitored peptides were: K[Poy]STGGK[1Ac]APR, K[Poy]STGGK[1Ac]APR-heavy, K[Poy]STGGK[Poy]APR and K[Poy]STGGK[Poy]APR-heavy. The absolute amounts of the acetylated and unmodified peptides were determined by comparing to the abundances of their SIL standards, that were added to the samples in the known concentrations, and, then used for calculation of H3K14Ac stoichiometry in CIC, CIM and MIM hMDM., Results: The assay was characterized by LLOD of 0.106 fmol/µL and 0.204 fmol/µL for unmodified and acetylated H3 9 KSTGGKAPR 17 peptides, respectively. The LLOQ was 0.5 fmol/µL and the linear range of the assay was from 0.5 to 2500 fmol/µL. The absolute abundances of the quantified peptides varied between the donors and conditions, and so did the H3K14Ac stoichiometry. This was rather attributed to the samples nature itself, as the variability of their triplicate measurements was low., Conclusions: The developed LC-MS/MS assay enabled absolute quantification of H3K14Ac in exposed to Meth HIV-infected hMDM. It can be further applied determination of this PTM stoichiometry in other studies on human primary macrophages., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Based on previous studies which failed to analyze important confounding variables, the association between preoperative anemia and outcomes of patients who underwent colorectal cancer (CRC) surgery has not been clearly demonstrated. This study aimed to investigate the relationship between preoperative anemia and short-term outcomes in patients with CRC., Methods: Data from a retrospective collective database of patients who underwent CRC surgery at our hospital between September 1, 2019 and September 30, 2021 were retrieved and analyzed, and the short-term postoperative outcomes of anemic (hemoglobin < 120 g dL - 1 for female, hemoglobin < 130 g dL - 1 for male) and non-anemic patients were analyzed, using a 1:1 propensity score matching (PSM) analysis., Results: After excluding some cases, the remaining 1894 patients had complete data available for analysis. The incidence of preoperative anemia was 39.8% (754/1894). Before PSM, preoperative anemia patients had a higher risk of major morbidity than non-anemia patients (27.2% vs. 23.1%, odds ratio [OR] 1.245, 95% confidence interval [CI] 1.008-1.538, P = 0.042). After PSM was performed in the cohort, 609 patients remained in the anemic and non-anemic groups. The incidence of major morbidity (25.8% vs. 24.0%, OR 1.102, 95% CI 0.849-1.429, P = 0.446) between anemic and non-anemic patients was comparable. No significant difference was found between the anemic and non-anemic groups in postoperative length of stay (8.0 [6.0-12.0] vs. 8.0 [7.0-11.0], P = 0.311). The sensitivity analysis results were in accordance with the primary outcome. Furthermore, we did not ascertain any discernible correlation between the extent of anemia and significant major morbidity., Conclusions: Compared with preoperative non-anemia, anemia status does not seem to be associated with major morbidity in patients with CRC surgery. It is noteworthy that, anemia is insufficient as a solitary risk factor and may be a better marker of poor health resulting from multiple factors., Trial Registration: Registration Authority: Chinese Clinical Trial Registry; Registration number and date: ChiCTR2100049696, 08/08/2021; Principal investigator: Ting Yan; Link to trial registry: http://www.chictr.org.cn/showproj.aspx?proj=131698 ; ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To explore the effect of oral comprehensive nursing intervention on mechanically ventilated patients in ICU., Methods: Select 76 cases of mechanically ventilated patients in severe ICU admitted to our hospital from January 2022 to October 2022 as the research objects, and divide them into the control group and the observation group according to the way the patients receive oral care. 38 cases each. The patients in the control group received routine nursing intervention, and the patients in the observation group received comprehensive oral nursing intervention on the basis of the nursing of the control group. The clinical index data, oropharyngeal hygiene, pH value, blood gas analysis index levels, and the occurrence and death of ventilator-associated pneumonia were compared between the two groups of patients., Results: The hospitalization time of the two groups was compared (P > 0.05); the mechanical ventilation time and ICU stay time of the observation group were significantly lower than those of the control group (all, P < 0.05); the oral odor scores, The plaque index and soft scale index were significantly lower than those of the control group (all, P < 0.05); the pH value, PaO 2 value, and SpO 2 value of the observation group were significantly lower than those of the control group, and the PaCO 2 value was significantly higher than that of the control group. group (all, P < 0.05); the incidence of VAP in the control group was 55.26%, and the mortality rate was 15.79%, the incidence rate of VAP in the observation group was 21.05%, and the mortality rate was 2.63%, and the incidence rate and mortality rate of VAP in the observation group were significantly lower in the control group (all, P < 0.05)., Conclusion: The application of nursing intervention can effectively promote the recovery of patients, improve the hygiene of patients' oropharynx, adjust the levels of pH and blood gas-related indicators in patients, and reduce VAP in patients. risk of morbidity and mortality., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Medical disputes remain a global public health problem. However, an analysis of the characteristics and risk factors affecting the judgment results of medical damage liability disputes in second-instance and retrial cases in China has yet to be conducted., Methods: We conducted a systematic search and evaluation of second-instance and retrial cases among all medical damage liability disputes in China Judgments Online; SPSS 22.0 was used for the statistical analysis. A χ 2 test or likelihood ratio Chi-square test was used to compare differences between groups, and multivariate logistic regression analysis was performed to determine independent risk factors that could affect the judgment results of medical disputes., Results: We included 3172 second-instance and retrial cases among all medical damage liability disputes in the analysis. The results showed that 48.04% of cases were unilateral appeals by the patient, and medical institutions were responsible for providing compensation in 80.64% of these cases. Cases involving compensation ranged from Chinese Yuan (CNY) 100 000 to 500 000 ranked first (40.95%); 21.66% were non-compensation cases. Cases involving mental damage compensation of less than CNY 20 000 accounted for 39.03%. Violations of medical treatment and nursing routines accounted for 64.25% of all cases. In addition, re-identification in 54.59% of cases changed the initial appraisal opinion. Independent risk factors for medical personnel to lose a lawsuit in a multivariate logistic regression model included appeal originator [patient side: OR = 18.809 (95% CI 11.854-29.845); both sides: OR = 22.168 (95% CI 12.249-40.117)], change of the original verdict (OR = 5.936, 95% CI 3.875-9.095), judicial identification (OR = 6.395, 95% CI 4.818-8.487), violations of medical treatment and nursing routines (OR = 8.783, 95% CI 6.658-11.588), and non-standard medical document writing (OR = 8.500, 95% CI 4.805-15.037)., Conclusion: Our study clarifies the characteristics of second-instance and retrial cases among all medical damage liability disputes in China from multiple perspectives and identifies the independent risk factors for medical personnel losing a lawsuit. This study could help medical institutions prevent and reduce medical disputes, at the same time, it could be helpful for medical institutions to provide better medical treatment and nursing services for patients., (© 2023. The Author(s).)

Background: RNA modification plays important roles in many biological processes, such as gene expression control. The aim of this study was to identify single nucleotide polymorphisms related to RNA modification (RNAm-SNPs) for rheumatoid arthritis (RA) as putative functional variants., Methods: We examined the association of RNAm-SNPs with RA in summary data from a genome-wide association study of 19,234 RA cases and 61,565 controls. We performed eQTL and pQTL analyses for the RNAm-SNPs to find associated gene expression and protein levels. Furthermore, we examined the associations of gene expression and circulating protein levels with RA using two-sample Mendelian randomization analysis methods., Results: A total of 160 RNAm-SNPs related to m 6 A, m 1 A, A-to-I, m 7 G, m 5 C, m 5 U and m 6 Am modifications were identified to be significantly associated with RA. These RNAm-SNPs were located in 62 protein-coding genes, which were significantly enriched in immune-related pathways. RNAm-SNPs in important RA susceptibility genes, such as PADI2, SPRED2, PLCL2, HLA-A, HLA-B, HLA-DRB1, HLA-DPB1, TRAF1 and TXNDC11, were identified. Most of these RNAm-SNPs showed eQTL effects, and the expression levels of 26 of the modifiable genes (e.g., PADI2, TRAF1, HLA-A, HLA-DRB1, HLA-DPB1 and HLA-B) in blood cells were associated with RA. Circulating protein levels, such as CFB, GZMA, HLA-DQA2, IL21, LRPAP1 and TFF3, were affected by RNAm-SNPs and were associated with RA., Conclusion: The present study identified RNAm-SNPs in the reported RA susceptibility genes and suggested that RNAm-SNPs may affect RA risk by affecting the expression levels of corresponding genes and proteins., (© 2023. The Author(s).)

Background: Root-knot nematodes (RKN) are among the most important root-damaging plant-parasitic nematodes, causing severe crop losses worldwide. The plant rhizosphere and root endosphere contain rich and diverse bacterial communities. However, little is known about how RKN and root bacteria interact to impact parasitism and plant health. Determining the keystone microbial taxa and their functional contributions to plant health and RKN development is important for understanding RKN parasitism and developing efficient biological control strategies in agriculture., Results: The analyses of rhizosphere and root endosphere microbiota of plants with and without RKN showed that host species, developmental stage, ecological niche, and nematode parasitism, as well as most of their interactions, contributed significantly to variations in root-associated microbiota. Compared with healthy tomato plants at different developmental stages, significant enrichments of bacteria belonging to Rhizobiales, Betaproteobacteriales, and Rhodobacterales were observed in the endophytic microbiota of nematode-parasitized root samples. Functional pathways related to bacterial pathogenesis and biological nitrogen fixation were significantly enriched in nematode-parasitized plants. In addition, we observed significant enrichments of the nifH gene and NifH protein, the key gene/enzyme involved in biological nitrogen fixation, within nematode-parasitized roots, consistent with a potential functional contribution of nitrogen-fixing bacteria to nematode parasitism. Data from a further assay showed that soil nitrogen amendment could reduce both endophytic nitrogen-fixing bacteria and RKN prevalence and galling in tomato plants., Conclusions: Results demonstrated that (1) community variation and assembly of root endophytic microbiota were significantly affected by RKN parasitism; (2) a taxonomic and functional association was found for endophytic nitrogen-fixing bacteria and nematode parasitism; and (3) the change of nitrogen-fixing bacterial communities through the addition of nitrogen fertilizers could affect the occurrence of RKN. Our results provide new insights into interactions among endophytic microbiota, RKN, and plants, contributing to the potential development of novel management strategies against RKN. Video Abstract., (© 2023. The Author(s).)

Background: Early metastasis is a hallmark of osteosarcoma (OS), a highly common type of malignant tumor. Members of the potassium inwardly rectifying channel family exert oncogenic effects in various cancers. However, the role of the potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) in OS is unclear., Methods: The expression of KCNJ2 in OS tissues and cell lines was measured using bioinformatic analysis, immunohistochemistry, and western blotting. Wound-healing assays, Transwell assays, and lung metastasis models were used to analyze the effects of KCNJ2 on mobility of OS cells. The molecular mechanisms linking KCNJ2 and HIF1α in OS were explored by mass spectrometry analysis, immunoprecipitation, ubiquitination detection, and chromatin-immunoprecipitation quantitative real-time polymerase chain reaction., Results: KCNJ2 was found to be overexpressed in advanced-stage OS tissues, as well as in cells with high metastatic potential. High expression of KCNJ2 was associated with a shorter survival rate of OS patients. KCNJ2-inhibition repressed the metastasis of OS cells, whereas KCNJ2-elevation induced the opposite effects. Mechanistically, KCNJ2 binds to HIF1α and inhibits its ubiquitination, thus increasing the expression of HIF1α. Interestingly, HIF1α binds directly to the KCNJ2 promoter and increases its transcription under hypoxic conditions., Conclusion: Taken together, our results indicated that a KCNJ2/HIF1α positive feedback loop exists in OS tissues, which significantly promotes OS cell metastasis. This evidence may contribute to the diagnosis and treatment of OS. Video Abstract., (© 2023. The Author(s).)

Background: Verticillium wilt, caused by the fungus Verticillium dahliae, leads to significant losses in cotton yield worldwide. Biocontrol management is a promising means of suppressing verticillium wilt. The purpose of the study was to obtain and analyze endophytic bacteria with Verticillium wilt-resistant activities from the roots of Gossypium barbadense 'Xinhai15' and to explore the interactions between the soil and plants., Results: An endophytic bacterium Bacillus sp. T6 was obtained from the Verticillium wilt-resistant cotton G. barbadense 'Xinhai15', which showed significant antagonistic abilities against cotton Verticillium wilt. The bioassay results indicated that the strain possessed strong antagonistic abilities that inhibited V. dahliae spore germination and mycelial growth without contact, and thus it was speculated that the active factor of the bacteria might be volatile compounds. A total of 46 volatile substances were detected via headspace solid-phase microextraction and gas chromatography-mass spectrometry analysis. The pure product verification experiment confirmed that the styrene produced by the T6 strain was the main virulence factor. Transcriptome analysis showed that following styrene induction, 247 genes in V. dahliae, including four hydrolase genes, eight dehydrogenase genes, 11 reductase genes, 17 genes related to transport and transfer were upregulated. Additionally, 72 genes, including two chitinase genes, two protease genes, five transport-related genes, and 33 hypothetical protein genes, were downregulated. The quantitative real-time PCR results confirmed that the expression of the four genes VDAG&#95;02838, VDAG&#95;09554, VDAG&#95;045572, and VDAG&#95;08251 was increased by 3.18, 78.83, 2.71, and 2.92 times, respectively, compared with the uninduced control group., Conclusions: The research provides a new reference for the development and application of the volatile compounds of endophytic bacteria as new biocontrol agents for the control of Verticillium wilt and as biological preservatives for agricultural products., (© 2023. The Author(s).)

Background: Sedative gastrointestinal endoscopy is extensively used worldwide. An appropriate degree of sedation leads to more acceptability and satisfaction. Artificial intelligence has rapidly developed in the field of digestive endoscopy in recent years and we have constructed a mature computer-aided diagnosis (CAD) system. This system can identify the remaining parts to be examined in real-time endoscopic procedures, which may help anesthetists use anesthetics properly to keep patients in an appropriate degree of sedation., Aims: This study aimed to evaluate the effects of the CAD system on anesthesia quality control during gastrointestinal endoscopy., Methods: We recruited 154 consecutive patients at Renmin Hospital of Wuhan University, including 76 patients in the CAD group and 78 in the control group. Anesthetists in the CAD group were able to see the CAD system's indications, while anesthetists in the control group could not. The primary outcomes included emergence time (from examination completion to spontaneous eye opening when doctors called the patients' names), recovery time (from examination completion to achievement of the primary recovery endpoints) and patient satisfaction scores. The secondary outcomes included anesthesia induction time (from sedative administration to successful sedation), procedure time (from scope insertion to scope withdrawal), total dose of propofol, vital signs, etc. This trial was registered in the Primary Registries of the WHO Registry Network, with registration number ChiCTR2100042621., Results: Emergence time in the CAD group was significantly shorter than that in the control group (p < 0.01). The recovery time was also significantly shorter in the CAD group (p < 0.01). Patients in the CAD group were significantly more satisfied with their sedation than those in control group (p < 0.01). Vital signs were stable during the examinations in both groups. Propofol doses during the examinations were comparable between the two groups., Conclusion: This CAD system possesses great potential for anesthesia quality control. It can improve patient satisfaction during endoscopic examinations with sedation., Trial Registration: ChiCTR2100042621., (© 2022. The Author(s).)

Background: Diabetic foot (DF) is one of the most common and serious complications of diabetes mellitus (DM), which brings great psychological and economic pressure to patients. This study aimed to evaluate the efficacy of stem cells in the treatment of diabetic foot., Methods: All relevant studies in Cochrane, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases were systematically searched for meta-analysis. The outcomes consisted of ulcer or wound healing rate, amputation rate, new vessels, ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), pain-free walking distance, and rest pain score. Dichotomous outcomes were described as risk ratios (RR) with 95% confidence intervals (CIs), while continuous data were presented as standardized mean differences (SMDs) with 95% CIs. Statistical analysis was performed with RevMan 5.3 software., Results: A total of 14 studies with 683 participants were included in the meta-analysis. Meta-analysis showed that stem cell therapy was more effective than conventional therapy in terms of ulcer or wound healing rate [OR = 8.20 (5.33, 12.62)], improvement in lower extremity ischemia(new vessels) [OR = 16.48 (2.88, 94.18)], ABI [MD = 0.13 (0.04, 0.08)], TcO2[MD = 4.23 (1.82, 6.65)], pain-free walking distance [MD = 220.79 (82.10, 359.48)], and rest pain score [MD = - 1.94 (- 2.50, - 1.39)], while the amputation rate was significantly decreased [OR = 0.19 (0.10, 0.36)]., Conclusions: The meta-analysis of the current studies has shown that stem cells are significantly more effective than traditional methods in the treatment of diabetic foot and can improve the quality of life of patients after treatment. Future studies should conduct large-scale, randomized, double-blind, placebo-controlled, multicenter trials with high-quality long-term follow-up to demonstrate the most effective cell types and therapeutic parameters for the treatment of diabetic foot., (© 2022. The Author(s).)

Background: To compare the effects of two biologic disease-modifying antirheumatic drug (bDMARD) administration strategies on the maintenance effect and safety of patients with rheumatoid arthritis (RA) in remission, to analyze the effects of gradual drug reduction and dose maintenance treatment on clinical outcomes in patients who have achieved remission with different types of bDMARDs, to search and screen out people who may benefit from drug reduction strategies, and to provide references for drug reduction strategies and treatment options for patients with RA in remission, so as to help improve the safety of the treatment and reduce the economic burden., Methods: The study will be a 24-month non-inferiority randomized, controlled, single-blind trial and is planned to be launched in our hospital from September 2021 to August 2023. Patients will be randomized in a ratio of 2:1 to two groups: maintenance or injection spacing by 50%/gradual reduction of dosage every 3 months up to complete stop. When the patient relapses, return to the last effective dose. If the remission can be maintained, the medication of bDMARDs can be stopped 9 months after enrollment. The primary outcome will be the persistent flare rate., Discussion: Our study may provide a reference for the selection of drug reduction strategies and treatment options for patients with RA in remission, so as to help improve the safety of the treatment and reduce the economic burden., Trial Registration: Chinese Clinical Trial Registry ChiCTR2100044751. Registered on 26 March 2021., (© 2022. The Author(s).)

Background: Genome-wide association studies (GWASs) have identified hundreds of loci for body mass index (BMI), but functional variants in these loci are less known. The purpose of this study was to identify RNA modification-related SNPs (RNAm-SNPs) for BMI in GWAS loci. BMI-associated RNAm-SNPs were identified in a GWAS of approximately 700,000 individuals. Gene expression and circulating protein levels affected by the RNAm-SNPs were identified by QTL analyses. Mendelian randomization (MR) methods were applied to test whether the gene expression and protein levels were associated with BMI., Results: A total of 78 RNAm-SNPs associated with BMI (P < 5.0 × 10 -8 ) were identified, including 65 m 6 A-, 10 m 1 A-, 3 m 7 G- and 1 A-to-I-related SNPs. Two functional loss, high confidence level m 6 A-SNPs, rs6713978 (P = 6.4 × 10 -60 ) and rs13410999 (P = 8.2 × 10 -59 ), in the intron of ADCY3 were the top significant SNPs. These two RNAm-SNPs were associated with ADCY3 gene expression in adipose tissues, whole blood cells, the tibial nerve, the tibial artery and lymphocytes, and the expression levels in these tissues were associated with BMI. Proteins enriched in specific KEGG pathways, such as natural killer cell-mediated cytotoxicity, the Rap1 signaling pathway and the Ras signaling pathway, were affected by the RNAm-SNPs, and circulating levels of some of these proteins (ADH1B, DOCK9, MICB, PRDM1, STOM, TMPRSS11D and TXNDC12) were associated with BMI in MR analyses., Conclusions: Our study identified RNAm-SNPs in BMI-related genomic loci and suggested that RNA modification may affect BMI by affecting the expression levels of corresponding genes and proteins., (© 2022. The Author(s).)

Background: Area postrema syndrome (APS) as the isolated manifestation in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy has been rarely reported., Case Presentation: A 61-year-old male patient presented with intractable hiccup. He was first admitted to the department of Gastroenterology because he had no symptoms other than hiccup. Then he was diagnosed with possible digestive system disease and started on treatment. 2 weeks later, his symptom didn't improve at all. After consultation, the patient was referred to our department. Cerebrospinal fluid (CSF) analysis revealed lymphocytes pleocytosis, elevated protein level. Cell-based assays demonstrated GFAP antibodies in blood and CSF. His symptom improved with steroid pulse therapy (methylprednisolone, 1 g for 5 days), followed by a gradual tapering of oral prednisolone. Three months after the initial presentation, he showed no relapses., Conclusions: We report atypical manifestation of autoimmune GFAP astrocytopathy which presented as APS, suggesting that autoimmune GFAP astrocytopathy should be added to the list of possible cause of APS., (© 2022. The Author(s).)

Background: A paucity of studies focused on the genetic association that tuberculosis (TB) patients with non-communicable diseases (NCDs) are more likely to be infected with Mycobacterium tuberculosis (MTB) with more potent virulence on anti-TB drug resistance than those without NCDs. The study aimed to document the predominant genotype, determine the association between MTB genotypes and NCD status and drug resistance., Methods: We conducted a molecular study in 105 TB patients based on a cross-sectional study focused on the comorbid relationship between chronic conditions and TB among 1773 subjects from September 1, 2019 to August 30, 2020 in Guizhou, China. The participants were investigated through face-to-face interviews, followed by NCDs screening. The DNA of MTB isolates was extracted prior to genotyping using 24 loci MIRU-VNTR. The subsequent evaluations were performed by phylogenetic trees, combined with tests of statistical power, Chi-square or Fisher and multivariate logistic regression analysis., Results: The Beijing family of Lineage 2 (East Asia) was the predominant genotype accounting for 43.8% (46/105), followed by Lineage 4 (Euro-America) strains, including Uganda I (34.3%, 36/105), and the NEW-1 (9.5%, 10/105). The proportion of Beijing strain in patients with and without NCDS was 28.6% (8/28) and 49.4% (38/77), respectively, with a statistical power test value of 24.3%. No significant association was detected between MTB genotype and NCD status. A low clustering rate (2.9%) was identified, consisting of two clusters. The rates of global, mono-, poly- and multi-drug resistance were 16.2% (17/105), 14.3% (15/105), 1.0% (1/105) and 4.8% (5/105), respectively. The drug-resistant rates of rifampicin, isoniazid, and streptomycin, were 6.7% (7/105), 11.4% (12/105) and 5.7% (6/105), respectively. Isoniazid resistance was significantly associated with the Beijing genotype of Lineage 2 (19.6% versus 5.1%)., Conclusions: The Lineage 2 East Asia/Beijing genotype is the dominant genotype of the local MTB with endogenous infection preponderating. Not enough evidence is detected to support the association between the MTB genotype and diabetes/hypertension. Isoniazid resistance is associated with the Lineage 2 East Asia/Beijing strain., (© 2022. The Author(s).)

Background: Regorafenib belongs to a sub-group of small-molecule multi-targeted tyrosine kinase inhibitors(TKIs). In various studies with respect to the side-effect of regorafenib, drug-associated proteinuria standardly qualified to be defined as nephrotic syndrome was rarely reported as well as the relation of regorafenib with the occurrence and development of thrombotic microangiopathy (TMA)., Case Presentation: In this case report and literature review, we presented a 62-year-old patient receiving regorafenib for metastatic colon cancer, manifesting abundant proteinuria, in which TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the first reported in terms of regorafenib-induced TMA confirmed by renal biopsy., Conclusion: This case indicates that regorafenib, a kind of TKIs may result in TMA, which is a rare but life-threatening complication of cancer treatment drug. Insights from this case might help physicians diagnose rare forms of TMA and adjust treatment for patients in a timely manner., (© 2022. The Author(s).)

Purpose: Uveal melanoma (UM) is an aggressive intraocular malignancy, leading to systemic metastasis in half of the patients. However, the mechanism of the high metastatic rate remains unclear. This study aimed to identify key genes related to metastasis and construct a gene-based signature for better prognosis prediction of UM patients., Methods: Weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression of genes primarily associated with metastasis of UM. Univariate, Lasso-penalized and multivariate Cox regression analyses were performed to establish a prognostic signature for UM patients., Results: The tan and greenyellow modules were significantly associated with the metastasis of UM patients. Significant genes related to the overall survival (OS) in these two modules were then identified. Additionally, an OS-predicting signature was established. The UM patients were divided into a low- or high-risk group. The Kaplan-Meier curve indicated that high-risk patients had poorer OS than low-risk patients. The receiver operating curve (ROC) was used to validate the stability and accuracy of the final five-gene signature. Based on the signature and clinical traits of UM patients, a nomogram was established to serve in clinical practice., Conclusions: We identified key genes involved in the metastasis of UM. A robust five-gene-based prognostic signature was constructed and validated. In addition, the gene signature-based nomogram was created that can optimize the prognosis prediction and identify possible factors causing the poor prognosis of high-risk UM patients., (© 2022. The Author(s).)

Background: The RNA profiles of tumor-educated platelets (TEPs) possess pathological features that could be used for early cancer detection. However, the utility of TEP RNA profiling in detecting early colorectal cancer (CRC) versus noncancerous colorectal diseases has not yet been investigated. This study assesses the diagnostic capacity of TEP RNA profiles in a cohort of patients with CRC and noncancerous diseases., Methods: Transcriptome sequencing for platelets isolated from 132 patients with CRC at early and late stages and 190 controls consisting of healthy donors and patients with ulcerative disease, Crohn's disease, polyps, and adenomas was performed and analyzed using binary particle swarm optimization coupled with support vector machine to identify genes that contributed to the classification of CRC patients versus controls. The area under the receiver operating curves (AUROCs) and the accuracy of TEP RNA profiles in CRC diagnosis were assessed., Results: TEP RNA profiling achieved high performance in distinguishing and staging CRC patients from the controls. Using the swarm intelligence algorithm, the 921 most contributive genes that classified CRC patients from the controls were identified. AUROCs of 0.928 for the training set via leave-one-out cross-validation and 0.92 for the validation set were achieved, both of which were significantly higher than the clinically utilized serum biomarkers: carcinoembryonic antigen and cancer antigen 19-9. Notably, an AUROC of 0.915 in an external validation set was achieved. For predicting different CRC stages, an AUROC of 0.984 was achieved in the training set and 1.000 in the internal validation set., Conclusions: RNA profiles of TEPs are of potential diagnostic value for identifying early CRC from noncancerous diseases. Prospective studies are needed to validate its clinical relevance., (© 2022. The Author(s).)

Background & Aims: To clarify the biological roles, circularization process and secretion pathway of circRHOBTB3 in colorectal cancer (CRC) progression., Methods: We performed a comprehensive analysis of circRNA levels in serum exosomes from multiple types of cancer patients in public databases and verified the higher level of circRHOBTB3 in CRC sera versus healthy donors by RT-qPCR. Then, the function of circRHOBTB3 in CRC was investigated in vitro and in vivo. RNA-seq and RNA pull-down assays together with mass spectrometry identified the downstream signals and the binding proteins of circRHOBTB3. Finally, Antisense oligonucleotides (ASOs) were designed to target circularization and secretion elements of circRHOBTB3 for CRC therapy., Results: circRHOBTB3 levels were increased in the sera but was downregulated in tissue samples in CRC, and the downregulation was associated with poor prognosis. Furthermore, circRHOBTB3 acts a tumor-suppressive circRNA by repressing metabolic pathways, intracellular ROS production in CRC. Several key elements were discovered to regulate circRHOBTB3 circularization and exosomal secretion. Moreover, SNF8 was identified that sorts circRHOBTB3 into exosomes. Interestingly, we found that CRC cells could actively secrete more circRHOBTB3 than normal cells. According to the sequence of regulatory elements for circularization and exosomal secretion, we designed and synthesized ASOs, which increased circRHOBTB3 expression and blocked circRHOBTB3 exosomal secretion. More importantly, ASOs could inhibit CRC growth and metastasis in vitro and in vivo., Conclusions: circRHOBTB3 plays a tumor-suppressive role in CRC and has to be excreted out of cells to sustain cancer cell fitness. ASOs targeting regulatory elements for circularization and exosomal secretion will become a novel antitumor strategy., (© 2022. The Author(s).)

Background: Sonodynamic therapy (SDT) has emerged as a noninvasive therapeutic modality that involves sonosensitizers and low-intensity ultrasound. However, owing to the rapid recombination of charge carriers, most of the sonosensitizers triggered poor reactive oxygen species (ROS) generation, resulting in unsatisfactory sonodynamic therapeutic effects., Results: Herein, a photo/sono-responsive nanoplatform was developed through the in-situ systhesis of TiO 2-x on the surface of two-dimensional MXene (titanium carbide, Ti 3 C 2 ) for photoacoustic/photothermal bimodal imaging-guided near-infrared II (NIR-II) photothermal enhanced SDT of tumor. Because of several oxygen vacancies and smaller size (~ 10 nm), the in-situ formed TiO 2-x nanoparticles possessed narrow band gap (2.65 eV) and high surface area, and thus served as a charge trap to restrict charge recombination under ultrasound (US) activation, resulting in enhanced sonodynamic ROS generation. Moreover, Ti 3 C 2 nanosheets induced extensive localized hyperthermia relieves tumor hypoxia by accelerating intratumoral blood flow and tumor oxygenation, and thus further strengthened the efficacy of SDT. Upon US/NIR-II laser dual-stimuli, Ti 3 C 2 @TiO 2-x nanoplatform triggered substantial cellular killing in vitro and complete tumor eradication in vivo, without any tumor recurrence and systemic toxicity., Conclusion: Our work presents the promising design of photo/sono-responsive nanoplatform for cancer nanotheranostics., (© 2022. The Author(s).)

Background: The broad continuum between tropical and temperate floras in Eastern Asia (EAS) are thought to be one of the main factors responsible for a prominent species diversity anomaly of temperate plants between EAS and eastern North America (ENS). However, how the broad continuum and niche evolution between tropical and temperate floras in EAS contributes to lineage divergence and species diversity remains largely unknown., Results: Population genetic structure, demography, and determinants of genetic structure [i.e., isolation-by-distance (IBD), isolation-by-resistance (IBR), and isolation-by-environment (IBE)] of Machilus thunbergii Sieb. et Zucc. (Lauraceae) were evaluated by examining sequence variation of ten low-copy nuclear genes across 43 populations in southeast China. Climatic niche difference and potential distributions across four periods (Current, mid-Holocene, the last glacial maximum, the last interglacial) of two genetic clusters were determined by niche modelling. North and south clusters of populations in M. thunbergii were revealed and their demarcation line corresponds well with the northern boundary of tropical zone in China of Zhu & Wan. The divergence time between the clusters and demographic expansion of M. thunbergii occurred after the mid-Pleistocene climate transition (MPT, 0.8-1.2 Ma). Migration rates between clusters were asymmetrical, being much greater from north to south than the reverse. Significant effects of IBE, but non-significant effects of IBD and IBR on population genetic divergence were detected. The two clusters have different ecological niches and require different temperature regimes., Conclusions: The north-south genetic differentiation may be common across the temperate-tropical boundary in southeast China. Divergent selection under different temperature regimes (possibly above and below freezing temperature in winter) could account for this divergence pattern. The broad continuum between tropical and temperate floras in EAS may have provided ample opportunities for tropical plant lineages to acquire freezing tolerance and to colonize the temperate regions during the late-Cenozoic global cooling. Our findings shed deeper insights into the high temperate plant species diversity in EAS., (© 2022. The Author(s).)

Background: Lipocalin-2 (LCN2) has a critical effect on obesity as well as its associated comorbidities. The present study focused on analyzing serum LCN2 levels of obese patients with nonalcoholic fatty liver disease (NAFLD) and on determining relationship of hepatic steatosis improvement with LCN2 levels after laparoscopic sleeve gastrectomy (LSG)., Methods: This work enrolled ninety patients with obesity and NAFLD. Twenty-three of them underwent LSG. Anthropometric and biochemical parameters and serum LCN2 levels were determined at baseline and those at 6-month post-LSG. Controlled attenuation parameter (CAP) measured by FibroScan was adopted for evaluating hepatic steatosis., Results: Among severe obesity patients, serum LCN2 levels were significantly increased (111.59 ± 51.16 ng/mL vs. 92.68 ± 32.68 ng/mL, P = 0.035). The CAP value was higher indicating higher liver fat content (360.51 ± 45.14 dB/m vs. 340.78 ± 45.02 dB/m, P = 0.044). With regard to surgical patients, liver function, glucose, and lipid levels were significantly improved after surgery. Serum LCN2 levels significantly decreased (119.74 ± 36.15 ng/mL vs. 87.38 ± 51.65 ng/mL, P = 0.001). Decreased CAP indicated a significant decrease in liver fat content (358.48 ± 46.13 dB/m vs. 260.83 ± 69.64 dB/m, P < 0.001). The decrease in LCN2 levels was significantly related to the reduced hepatic fat content and improvement in steatosis grade after adjusting for gender, age, and BMI decrease., Conclusions: Serum LCN2 levels are related to obesity and NAFLD. The decreased serum LCN2 levels could be an indicator of hepatic steatosis improvement., (© 2022. The Author(s).)

Aim: This study aims to develop an instrument to measure infectious disease specialist nurses' core competence and examining the scale's validity and reliability., Background: With the increase of infectious diseases, more and more attention has been paid to infectious disease nursing care. The core competence of the infectious disease specialist nurses is directly related to the quality of nursing work. In previous researches, infectious disease specialist nurses' core competence was measured by the tools developed for general nurses instead of specialized tools, which made it difficult to clarify the core competence of nurses in infectious diseases department., Methods: Preliminary items were developed through literature review, theoretical research, qualitative interview and Delphi method. The confirmed 47 items were applied in the two rounds of data collection. Evaluation data on 516 infectious disease specialist nurses' core competence in the first round were utilized to preliminarily evaluate and explore the scale's constrution, while evaluation data on 497 infectious disease specialist nurses' core competence in the second round were utilized to do reliability analysis and validity analysis. In this study, factor analysis, Cronbach's α, Pearson correlation coefficients were all adopted., Results: The final scale is composed of 34 items and 5 factors, and adopted the 5-point scoring method. The factors are Professional Development Abilities, Infection Prevention and Control Abilities, Nursing Abilities for Infectious Diseases, Professionalism and Humanistic Accomplishment, and Responsiveness to Emergency Infectious Diseases. The explanatory variance of the five factors was 75.569%. The reliability and validity of the scale is well validated. The internal consistency, split-half reliability and test-retest reliability were 0.806, 0.966 and 0.831 respectively. The scale has good structural validity and content validity. The content validity was 0.869. Discrimination analysis showed that there were significant differences in the scores of core competence and its five dimensions among infectious disease specialist nurses of different ages, working years in infectious diseases, titles, educational background, marital status and wages (all P < 0.05)., Conclusions: The proposed scale takes on high reliability and validity, and is suitable for assessing the infectious disease specialist nurses' core competence., Relevance to Clinical Practice: This scale provides a reference for clinical assessment of infectious disease nursing., (© 2021. The Author(s).)

Objective: To investigate the effect of Helicobacter pylori (H. pylori) eradication on the prognosis of postoperative early gastric cancer (EGC)., Methods: This is a retrospective study based on data from 6 hospitals. We identified 429 patients with EGC who underwent curative gastrectomy from January 2010 to December 2016. All of the patients were tested for H. pylori. Patients were divided into two groups, the successful H. pylori eradication group (group A, 268 patients) and the non-H. pylori eradication group (group B, 161 patients), for calculating the disease-free survival (DFS) and overall survival (OS) of each group., Result: Positive node metastasis (hazard ratio (HR), 3.13; 95% confidence interval (CI), 1.84-5.32; P < 0.001), undifferentiated type (HR, 2.54; 95% CI, 1.51-4.28; P < 0.001), and non-H. pylori eradication (HR, 1.73; 95% CI, 1.08-2.77; P = 0.023) were statistically significantly independent risk factors of recurrence. Patient's age ≥60 years old (HR, 3.32; 95% CI, 2.00-5.53; P < 0.001), positive node metastasis (HR, 3.71; 95% CI, 2.25-6.12; P < 0.001), undifferentiated type (HR, 3.06; 95% CI, 1.79-5.23; P < 0.001), and non-H. pylori eradication (HR, 1.83; 95% CI, 1.11-3.02; P = 0.018) were statistically significantly independent risk factors of overall survival., Conclusion: H. pylori eradication treatment could prevent the recurrence of postoperative EGC to prolong the overall survival of patients with EGC., (© 2021. The Author(s).)

Background: Acute kidney injury (AKI) with high mortality rates is associated with an excess of reactive oxygen/nitrogen species (RONS) within kidney tissues. Recently, nanomedicine antioxidant therapy has been used to alleviate AKI. Herein, we synthesized ultrasmall Prussian blue nanozymes (PB NZs, 4.5 nm) as theranostic agents for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided AKI treatment., Results: PB NZs exhibited multi-enzyme mimetic abilities, promoting the effective elimination of RONS both in vitro and in vivo. Moreover, benefiting from their imaging contrast properties, the rapid renal accumulation of PB NZs was verified by in vivo PA/MR dual-modal imaging. Due to their excellent enrichment in the kidney and unique multi-enzyme mimetic abilities, ultrasmall PB NZs displayed superior AKI treatment efficacy compared with that of amifostine in two clinically relevant types of AKI induced murine models (either by rhabdomyolysis or cisplatin)., Conclusion: Our findings suggested ultrasmall PB NZs, as nanozyme theranostics, have great potential for AKI management., (© 2021. The Author(s).)

Background: Biogeochemical exports from watersheds are modulated by the activity of microorganisms that function over micron scales. Here, we tested the hypothesis that meander-bound regions share a core microbiome and exhibit patterns of metabolic potential that broadly predict biogeochemical processes in floodplain soils along a river corridor., Results: We intensively sampled the microbiomes of floodplain soils located in the upper, middle, and lower reaches of the East River, Colorado. Despite the very high microbial diversity and complexity of the soils, we reconstructed 248 quality draft genomes representative of subspecies. Approximately one third of these bacterial subspecies was detected across all three locations at similar abundance levels, and ~ 15% of species were detected in two consecutive years. Within the meander-bound floodplains, we did not detect systematic patterns of gene abundance based on sampling position relative to the river. However, across meanders, we identified a core floodplain microbiome that is enriched in capacities for aerobic respiration, aerobic CO oxidation, and thiosulfate oxidation with the formation of elemental sulfur. Given this, we conducted a transcriptomic analysis of the middle floodplain. In contrast to predictions made based on the prominence of gene inventories, the most highly transcribed genes were relatively rare amoCAB and nxrAB (for nitrification) genes, followed by genes involved in methanol and formate oxidation, and nitrogen and CO 2 fixation. Within all three meanders, low soil organic carbon correlated with high activity of genes involved in methanol, formate, sulfide, hydrogen, and ammonia oxidation, nitrite oxidoreduction, and nitrate and nitrite reduction. Overall, the results emphasize the importance of sulfur, one-carbon and nitrogen compound metabolism in soils of the riparian corridor., Conclusions: The disparity between the scale of a microbial cell and the scale of a watershed currently limits the development of genomically informed predictive models describing watershed biogeochemical function. Meander-bound floodplains appear to serve as scaling motifs that predict aggregate capacities for biogeochemical transformations, providing a foundation for incorporating riparian soil microbiomes in watershed models. Widely represented genetic capacities did not predict in situ activity at one time point, but rather they define a reservoir of biogeochemical potential available as conditions change. Video abstract.

Background: Gastric intestinal metaplasia (GIM) is a significant risk factor for gastric cancer. Risk of gastric cancer/dysplasia between complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM) was controversial. Our study aimed to pool relative risk (RR) of cancer/dysplasia of IIM compared with CIM in GIM patients., Methods: PubMed, EMBASE, Cochrane Library and Web of Science were searched for studies concerning cancer/dysplasia in GIM patients. Random-effects or fixed-effects model was utilized for pooling RR. Sensitivity and publication bias analyses were conducted. Stability of results would be evaluated in case of publication bias., Results: 12 studies were included. Compared with CIM, pooled RR of cancer/dysplasia in IIM patients was 4.48 (95% CI 2.50-8.03), and the RR was 4.96 (95% CI 2.72-9.04) for cancer, and 4.82 (95% CI 1.45-16.0) for dysplasia. The pooled RR for cancer/dysplasia in type III IM was 6.27 (95% CI 1.89-20.77) compared with type II + I IM, while it was 5.55 (95% CI 2.07-14.92) compared with type II IM. Pooled RR between type II IM and type I IM was 1.62 (95% CI 1.16-2.27). Subgroup analyses showed that IIM was associated with a higher risk of gastric cancer/dysplasia in Western population (pooled RR = 4.65 95% CI 2.30-9.42), but not in East Asian population (pooled RR = 4.01 95% CI 0.82-19.61)., Conclusions: IIM was related to a higher risk of cancer/dysplasia compared with CIM. Risk of developing cancer/dysplasia from type I, II, and III intestinal metaplasia increased gradually.

Background: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai., Method: Male ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (-/-) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the human ApoE Sendai and ApoE Kyoto, apoE3, and eGFP genes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin-creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed., Results: After virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4-6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin-creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (-/-) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation., Conclusions: In this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.