Showing papers by "Xiaoyan Jiang published in 2022"

The impact of hyperglycaemic crisis episodes on long-term outcomes for inpatients presenting with acute organ injury: A prospective, multicentre follow-up study

Abstract: Background The long-term clinical outcome of poor prognosis in patients with diabetic hyperglycaemic crisis episodes (HCE) remains unknown, which may be related to acute organ injury (AOI) and its continuous damage after hospital discharge. This study aimed to observe the clinical differences and relevant risk factors in HCE with or without AOI. Methods A total of 339 inpatients were divided into an AOI group (n=69) and a non-AOI group (n=270), and their differences and risk factors were explored. The differences in clinical outcomes and prediction models for evaluating the long-term adverse events after hospital discharge were established. Results The mortality among cases complicated by AOI was significantly higher than that among patients without AOI [8 (11.59%) vs. 11 (4.07%), Q = 0.034] during hospitalization. After a 2-year follow-up, the mortality was also significantly higher in patients with concomitant AOI than in patients without AOI after hospital discharge during follow-up [13 (21.31%) vs. 15 (5.8%), Q < 0.001]. The long-term adverse events in patients with concomitant AOI were significantly higher than those in patients without AOI during follow-up [15 (24.59%) vs. 31 (11.97%), Q = 0.015]. Furthermore, Blood β-hydroxybutyric acid (P = 0.003), Cystatin C (P <0.001), serum potassium levels (P = 0.001) were significantly associated with long-term adverse events after hospital discharge. Conclusions The long-term prognosis of HCE patients complicated with AOI was significantly worse than that of HCE patients without AOI. The laboratory indicators were closely correlated with AOI, and future studies should explore the improvement of clinical outcome in response to timely interventions.

Application of engineered extracellular vesicles for targeted tumor therapy

Abstract: All cells, including prokaryotes and eukaryotes, could release extracellular vesicles (EVs). EVs contain many cellular components, including RNA, and surface proteins, and are essential for maintaining normal intercellular communication and homeostasis of the internal environment. EVs released from different tissues and cells exhibit excellent properties and functions (e.g., targeting specificity, regulatory ability, physical durability, and immunogenicity), rendering them a potential new option for drug delivery and precision therapy. EVs have been demonstrated to transport antitumor drugs for tumor therapy; additionally, EVs' contents and surface substance can be altered to improve their therapeutic efficacy in the clinic by boosting targeting potential and drug delivery effectiveness. EVs can regulate immune system function by affecting the tumor microenvironment, thereby inhibiting tumor progression. Co-delivery systems for EVs can be utilized to further improve the drug delivery efficiency of EVs, including hydrogels and liposomes. In this review, we discuss the isolation technologies of EVs, as well as engineering approaches to their modification. Moreover, we evaluate the therapeutic potential of EVs in tumors, including engineered extracellular vesicles and EVs' co-delivery systems.

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Abstract: The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (m6A) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development. Compelling evidence indicates that m6A methylation regulates transcription and protein expression through shearing, export, translation, and processing, thereby participating in the dynamic evolution of TME. Specifically, m6A methylation-mediated adaptation to hypoxia, metabolic dysregulation, and phenotypic shift of immune cells synergistically promote the formation of an immunosuppressive TME that supports tumor proliferation and metastasis. In this review, we have focused on the involvement of m6A methylation in the dynamic evolution of tumor-adaptive TME and described the detailed mechanisms linking m6A methylation to change in tumor cell biological functions. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m6A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m6A methylation research.

Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study

Abstract: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) are readily available circulatory immunity markers that are associated with components of frailty. However, few studies have investigated the relationship between these immunity markers and frailty, and it remains unknown whether they are predictive of incident frailty in older adults in general. Hence, we aimed to examine the association of these immunity markers with the risk of incident frailty.Overall, 1822 older adults (mean age was 78.03 ± 4.46 years) were included in the Rugao Longitudinal Aging Study. NLR, PLR and SII were calculated from blood cell counts. The frailty definition was based on the Fried phenotype. At baseline, 200 (10.98%) individuals were defined as frailty, and no significant associations of NLR, PLR and SII with frailty were found. During the 2-year follow-up, 180 (15.67%) individuals were new-onset frailty. After adjustment, an increased logNLR (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.20-7.18), logPLR (OR 2.54, 95% CI: 1.01-6.53) and logSII (OR 2.34, 95% CI: 1.16-4.78) were significantly associated with a higher risk of incident frailty in all individuals. Additionally, the associations of logNLR (OR 4.21, 95% CI 1.54-11.62 logPLR (OR 3.38, 95% CI: 1.17-9.91) and logSII (OR 2.56, 95% CI: 1.15-5.72) with incident frailty were remained after excluding individuals with comorbidities. In further analyzed, individuals with higher levels of NLR and SII had higher risk of incident frailty when we stratified individuals by quartiles of these immunity markers.NLR and SII are easily obtained immunity markers that could be used to predict incident frailty in clinical practice.

The Evaluation of Gait and Balance for Patients with Early Diabetic Peripheral Neuropathy: A Cross-Sectional Study

Abstract: Objective Falls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood. Methods A total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups. Results Stride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p<0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p<0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p<0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p<0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p<0.05). Conclusion The abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs. Clinical Trial Registration Number No. ChiCTR1800019179, www.chictr.org.cn.

Mechanisms of linezolid resistance in Staphylococcus capitis with the novel mutation C2128T in the 23S rRNA gene in China

Abstract: Abstract Purpose The objective of this study was to investigate the molecular characteristics and potential resistance mechanisms of linezolid-resistant (LZR) Staphylococcus capitis isolates from a tertiary hospital in China. Methods S. capitis isolates were obtained from clinical patient specimens; three of the isolates came from blood cultures and one from the hydrothorax. The agar dilution and E-test methods were used to identify antibiotic resistance. The chloramphenicol-florfenicol resistance ( cfr ) gene carrier status of the strains was determined by PCR. Whole-genome sequencing (WGS) was used to identify point mutations and L3, L4, and L22 mutations and to study the genetic environment of the cfr gene and the relationships between strains. Results The 4 isolates obtained in this study were all linezolid-resistant Staphylococcus strains. A similar of susceptibility profile pattern was observed in all four S. capitis strains, each of which exhibited a multidrug-resistant phenotype. A potentially novel mutation, C2128T, was identified, and the cfr genes of S. capitis strains were all positive. Additionally, the same mutations (C2128T and G2600T) were identified in all 23S rRNA sequences of the isolates, whereas mutations were lacking in the L3, L4, and L22 ribosomal proteins. The genetic environments surrounding cfr were identical in all four isolates. A schematic diagram of the phylogenetic tree showed that they were closely related to AYP1020, CR01, and TW2795, and a total of seven drug resistance genes were identified in these strains. Conclusions The study indicated that the resistance of the Staphylococcus capitis strains to linezolid was caused by multiple mechanisms, and a potential novel mutation, C2128T, that may have an impact on bacterial resistance was identified.

Mechanisms of linezolid resistance in Staphylococcus capitis with the novel mutation C2128T in the 23S rRNA gene in China

Abstract: Abstract Purpose The objective of this study was to investigate the molecular characteristics and potential resistance mechanisms of linezolid-resistant (LZR) Staphylococcus capitis isolates from a tertiary hospital in China. Methods S. capitis isolates were obtained from clinical patient specimens; three of the isolates came from blood cultures and one from the hydrothorax. The agar dilution and E-test methods were used to identify antibiotic resistance. The chloramphenicol-florfenicol resistance ( cfr ) gene carrier status of the strains was determined by PCR. Whole-genome sequencing (WGS) was used to identify point mutations and L3, L4, and L22 mutations and to study the genetic environment of the cfr gene and the relationships between strains. Results The 4 isolates obtained in this study were all linezolid-resistant Staphylococcus strains. A similar of susceptibility profile pattern was observed in all four S. capitis strains, each of which exhibited a multidrug-resistant phenotype. A potentially novel mutation, C2128T, was identified, and the cfr genes of S. capitis strains were all positive. Additionally, the same mutations (C2128T and G2600T) were identified in all 23S rRNA sequences of the isolates, whereas mutations were lacking in the L3, L4, and L22 ribosomal proteins. The genetic environments surrounding cfr were identical in all four isolates. A schematic diagram of the phylogenetic tree showed that they were closely related to AYP1020, CR01, and TW2795, and a total of seven drug resistance genes were identified in these strains. Conclusions The study indicated that the resistance of the Staphylococcus capitis strains to linezolid was caused by multiple mechanisms, and a potential novel mutation, C2128T, that may have an impact on bacterial resistance was identified.

The Predictive Value of Neutrophil-Lymphocyte Ratio in Patients with Polycythemia Vera at the Time of Initial Diagnosis for Thrombotic Events

Abstract: Objective To investigate and discuss the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in patients with polycythemia vera (PV) at the time of initial diagnosis, as well as its clinical significance in predicting the occurrence of thrombotic events and the progression of future thrombotic events during follow-ups, with the goal of providing a reference for the early identification of high-risk PV patients and the early intervention necessary to improve the prognosis of PV patients. Method A total of 170 patients diagnosed with PV for the first time were enrolled in this study. The risk factors affecting the occurrence and development of thrombotic events in these patients were statistically analyzed. Results NLR (P = 0.030), WBC count (P = 0.045), and history of previous thrombosis (P < 0.001) were independent risk factors for thrombotic events at the time of initial diagnosis. Age ≥ 60 years (P = 0.004), NLR (P = 0.025), history of previous thrombosis (P < 0.001), and fibrinogen (P = 0.042) were independent risk factors for the progression of future thrombotic events during follow-ups. The receiver operating characteristic curve (ROC curves) showed that NLR was more effective in predicting the progression of future thrombotic events than age ≥ 60 years, history of previous thrombosis, and fibrinogen. Kaplan-Meier survival analysis showed progression-free survival time of thrombotic events in the high NLR value group (NLR ≥ 4.713) (median survival time 22.033 months, 95% CI: 4.226-35.840), which was significantly lower compared to the low NLR value group (NLR < 4.713) (median overall survival time 66.000 months, 95% CI: 50.670-81.330); the observed difference was statistically significant (P < 0.001). The 60-month progression-free survival in the low NLR value group was 58.8%, while it was 32.8% in the high NLR value group. Conclusion Peripheral blood NLR levels in patients with PV resulted as an independent risk factor for the occurrence of thrombotic events at the time of initial diagnosis and for the progression of future thrombotic events during follow-ups. Peripheral blood NLR levels at the time of initial diagnosis and treatment had better diagnostic and predictive value for the progression of future thrombotic events in patients with PV than age ≥ 60 years, history of previous thrombosis, and fibrinogen.

Characterization of the Ferroptosis-Related Genes for Prognosis and Immune Infiltration in Low-Grade Glioma

Abstract: Background: Although ferroptosis has been validated to play a crucial role in some types of tumors, the influence of ferroptosis-related genes (FRGs) on the immune microenvironment in low-grade glioma (LGG) remains unclear. In this research, we screen the FRGs to assess the prognosis value and immune microenvironment in LGG, to provide reliable diagnosis and treatment evidence for the clinic. Methods: A total of 1,239 patients of LGG samples were selected for subsequent analyses from The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and the Repository of Molecular Brain Neoplasia Data datasets. Univariate Cox regression analysis was used to screen for prognostic FRGs. Consensus clustering was utilized to determine ferroptosis subtypes of LGG patients. Next, the prognostic model was constructed based on differentially expressed FRGs and validation in the validating datasets. The immune microenvironment, biological pathway, and hypoxia score were explored by single-sample gene set enrichment analysis. The potential response of chemotherapy and immune checkpoint blockade therapy was also estimated. In addition, the correlation between the risk score and autophagy-related genes was examined by the Pearson correlation coefficient. Results: A total of three ferroptosis subtypes were identified by consensus clustering for prognostic FRGs which exhibited different outcomes, clinicopathological characteristics, and immune microenvironment. Afterward, a prognostic model that performed great predictive ability based on nine prognostic FRGs has been constructed and validated. Moreover, the prognostic model had the potential to screen the sensitivity to chemotherapy and immunotherapy in LGG patients. Finally, we also found that the prognostic model has a great connection to autophagy and hypoxia. Conclusion: We developed a ferroptosis-related prognostic model which strongly linked to diagnosis, treatment, prognosis, and recurrence of LGG. This study also reveals the connection between ferroptosis and tumor immune microenvironment.

CEBPD modulates the airway smooth muscle transcriptomic response to glucocorticoids

Abstract: Abstract Background CCAAT/Enhancer Binding Protein D (CEBPD), a pleiotropic glucocorticoid-responsive transcription factor, modulates inflammatory responses. Of relevance to asthma, expression of CEBPD in airway smooth muscle (ASM) increases with glucocorticoid exposure. We sought to characterize CEBPD -mediated transcriptomic responses to glucocorticoid exposure in ASM by measuring changes observed after knockdown of CEBPD and its impact on asthma-related ASM function. Methods Primary ASM cells derived from four donors were transfected with CEBPD or non-targeting (NT) siRNA and exposed to vehicle control, budesonide (100 nM, 18 h), TNFα (10 ng/ml, 18 h), or both budesonide and TNFα. Subsequently, RNA-Seq was used to measure gene expression levels, and pairwise differential expression results were obtained for exposures versus vehicle and knockdown versus control conditions. Weighted gene co-expression analysis was performed to identify groups of genes with similar expression patterns across the various experimental conditions (i.e., CEBPD knockdown status, exposures). Results CEBPD knockdown altered expression of 3037 genes under at least one exposure (q-value < 0.05). Co-expression analysis identified sets of 197, 152 and 290 genes that were correlated with CEBPD knockdown status, TNFα exposure status, and both, respectively. JAK-STAT signaling pathway genes, including IL6R and SOCS3, were among those influenced by both TNFα and CEBPD knockdown. Immunoblot assays revealed that budesonide-induced IL-6R protein expression and augmented IL-6-induced STAT3 phosphorylation levels were attenuated by CEBPD knockdown in ASM. Conclusions CEBPD modulates glucocorticoid responses in ASM, in part via modulation of IL-6 receptor signaling.

Berberine enhances the anti-hepatocellular carcinoma effect of NK92-MI cells through inhibiting IFN-gamma-mediated PD-L1 expression

Abstract: Berberine is one of the most promising clinically tested natural alkaloids, and immunotherapy using natural killer (NK) cells is a potentially effective treatment for hepatocellular carcinoma (HCC). This study aims to elucidate the effect of berberine on the anti-HCC effect of NK92-MI cells. Human HCC SMMC-7721 and Hep3B cells were co-incubated with NK92-MI cells, berberine (60 or 80 μmol/L), or their combination for 36 h. To evaluate the killing effect of NK92-MI cells on HCC cells, the release of lactate dehydrogenase (LDH) in HCC cells was measured. The anti-tumor effects of berberine, NK92-MI cells, and their combinations were evaluated by MTS, EdU, Tunel, and Western blot assays. A male BALB/c nude mouse subcutaneous tumor model was used to investigate the anti-HCC effect of berberine and NK92-MI cells in vivo. The LDH assay showed that berberine enhanced the cytotoxicity of NK92-MI cells on HCC cells. The combination of berberine and NK92-MI cells demonstrated more obvious anti-HCC effect than did the berberine or NK92-MI single treatment in inhibiting cell proliferation and inducing apoptosis both in vitro and in vivo. Mechanistically, the expression of programmed cell death-ligand 1 (PD-L1) in HCC cells was upregulated after co-culture with NK-92MI cells. PD-L1 expression was knocked down, thereby inhibiting the proliferation and promoting apoptosis of HCC cells, and inhibited by berberine that blocked the secretion of interferon gamma (IFN-γ), thereby enhancing the anti-tumor effect of NK92-MI cells. Current data show that the immunomodulatory role of berberine is to enhance the cytotoxic effect of NK92-MI cells and inhibit tumor immune escape by reducing the expression of PD-L1. Our study provides a rationale for the clinical application of berberine in combination with NK cells for the treatment of HCC.

Favourable outcome of multisystem venous thrombosis associated with novel SERPINC1 mutation after treated with dabigatran: a case report with 7-year follow-up

Abstract: Abstract Background Mutations in SERPINC1 lead to deficiency in antithrombin (AT) which is an endogenous anticoagulant of normal hemostasis and could result in venous thromboembolism (VTE). Case presentation A 61-year-old male patient with recurrent thrombosis returned to the hospital with multiple cerebral thrombosis after voluntary cessation of dabigatran therapy. Laboratory tests revealed a type I AT deficiency in this patient and further whole exome sequencing (WES) identified a novel heterozygous frameshift duplication (c.233_236dup, p.Val80Alafs*26) in SERPINC1 gene. Long-term dabigatran treatment was given and no recurrence or side effects were found within the followed 5 years. Conclusion A multisystem VTE patient with a novel SERPINC1 mutation (c.233_236dup, p.Val80Alafs*26) reached a favourable outcome after dabigatran treatment.

Properties of Leukemic Stem Cells in Regulating Drug Resistance in Acute and Chronic Myeloid Leukemias

Abstract: Notoriously known for their capacity to reconstitute hematological malignancies in vivo, leukemic stem cells (LSCs) represent key drivers of therapeutic resistance and disease relapse, posing as a major medical dilemma. Despite having low abundance in the bulk leukemic population, LSCs have developed unique molecular dependencies and intricate signaling networks to enable self-renewal, quiescence, and drug resistance. To illustrate the multi-dimensional landscape of LSC-mediated leukemogenesis, in this review, we present phenotypical characteristics of LSCs, address the LSC-associated leukemic stromal microenvironment, highlight molecular aberrations that occur in the transcriptome, epigenome, proteome, and metabolome of LSCs, and showcase promising novel therapeutic strategies that potentially target the molecular vulnerabilities of LSCs.

Multiple gene knockdown strategies for investigating the properties of human leukemia stem cells and exploring new therapies.

Abstract: The past two decades have witnessed significant strides in leukemia therapies through approval of therapeutic inhibitors targeting oncogene-driving dysregulated tyrosine kinase activities and key epigenetic and apoptosis regulators. Although these drugs have brought about complete remission in the majority of patients, many patients face relapse or have refractory disease. The main factor contributing to relapse is the presence of a small subpopulation of dormant drug-resistant leukemia cells that possess stem cell features (termed as leukemia stem cells or LSCs). Thus, overcoming drug resistance and targeting LSCs remain major challenges for curative treatment of human leukemia. Chronic myeloid leukemia (CML) is a good example, with rare, propagating LSCs and drug-resistant cells that cannot be eradicated by BCR-ABL-directed tyrosine kinase inhibitor (TKI) monotherapy and that are responsible for disease relapse/progression. Therefore, it is imperative to identify key players in regulating BCR-ABL1-dependent and independent drug-resistance mechanisms, and their key pathways, so that CML LSCs can be selectively targeted or sensitized to TKIs. Here, we describe several easily adaptable gene knockdown approaches in CD34+ CML stem/progenitor cells that can be used to investigate the biological properties of LSCs and molecular effects of genes of interest (GOI), which can be further explored as therapeutic modalities against LSCs in the context of human leukemia.