Yu Zhao’s research while affiliated with Beijing children's hospital of Capital Medical University and other places

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Publications (9)


The flow chart for inclusion and exclusion of patients.
The receiver operating characteristic curves explore the value of preoperative inflammatory biomarkers in predicting intravesical recurrence after radical nephroureterectomy.
Kaplan-Meier curves for the prognosis by platelet-to-lymphocyte ratio. (A) Kaplan-Meier curves for intravesical recurrence-free survival by platelet-to-lymphocyte ratio (PLR); (B) Kaplan-Meier curves for recurrence-free survival by PLR; (C) Kaplan-Meier curves for overall survival by PLR.
The Kaplan–Meier curves of intravesical recurrence-free survival in different subgroups. (A) Kaplan-Meier curves for intravesical recurrence-free survival by platelet-to-lymphocyte ratio (PLR) in males; (B) Kaplan-Meier curves for intravesical recurrence-free survival by platelet-to-lymphocyte ratio (PLR) in females; (C) Kaplan-Meier curves for intravesical recurrence-free survival by platelet-to-lymphocyte ratio (PLR) in low-grade group; (D) Kaplan-Meier curves for intravesical recurrence-free survival by platelet-to-lymphocyte ratio (PLR) in high-grade group.
Predictive Value of the Platelet-Lymphocyte Ratio for Intravesical Recurrence After Radical Nephroureterectomy: A Retrospective Study
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December 2024

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7 Reads

Yu Zhao

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Xin Zhang

Objective The aim of this study was to evaluate the impact of preoperative platelet lymphocyte ratio (PLR) on the prognosis of patients after radical nephrectomy (RNU). Methods We retrospectively analyzed clinical data from 226 patients without a history of bladder cancer who underwent RNU at Beijing Chaoyang Hospital, Capital Medical University between January 2009 and December 2020. Patients were stratified into two groups (A low PLR group (n = 174) and a high PLR group (PLR ≥ 169.4) based on an optimal PLR threshold (PLR=169.4). The predictive accuracy of inflammatory biomarkers was assessed using receiver operating characteristic curves. Univariate and multivariate Cox proportional risk analyses were used to estimate the effect of PLR on intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), and overall survival (OS). The effect of PLR on IVRFS, RFS and OS was further examined using Kaplan-Meier survival curve analysis. Results The study cohort comprised 226 individuals with a mean age of 67.2 ± 9.8, 113 (50%) males and 113 (50%) females, 68 (30.1%) low-grade tumors and 158 (69.9%) high-grade tumors. In this study, 81 patients (36.7%) relapsed and 73 patients (32.3%) died. The area under the curve for PLR prediction of IVRFS was 0.603, superior to other inflammatory biomarkers. Multivariate analysis showed that PLR > 169.4 independently increased the risk of IVR after RNU, resulting in lower IVRFS [2.028 (1.014–4.057), P = 0.046], RFS [1.900 (1.168–3.090), P = 0.010], and OS [1.866 (1.099–3.167), P = 0.021]. In addition, survival analysis showed lower IVRFS [8.815 (62.722–97.278), P = 0.007], RFS [12.084 (44.315–91.685), P = 0.003] and OS RFS [10.165 (62.077–101.923), P = 0.005] in the low PLR group. Conclusion Elevated preoperative PLR is strongly associated with prognosis in patients with upper urothelial carcinoma (UTUC) after RNU without a history of bladder cancer.

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mNGS workflow in clinical application. CNS, Central nervous system.
Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases

November 2024

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66 Reads

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11 Citations

Metagenomic next-generation sequencing (mNGS) is a transformative approach in the diagnosis of infectious diseases, utilizing unbiased high-throughput sequencing to directly detect and characterize microbial genomes from clinical samples. This review comprehensively outlines the fundamental principles, sequencing workflow, and platforms utilized in mNGS technology. The methodological backbone involves shotgun sequencing of total nucleic acids extracted from diverse sample types, enabling simultaneous detection of bacteria, viruses, fungi, and parasites without prior knowledge of the infectious agent. Key advantages of mNGS include its capability to identify rare, novel, or unculturable pathogens, providing a more comprehensive view of microbial communities compared to traditional culture-based methods. Despite these strengths, challenges such as data analysis complexity, high cost, and the need for optimized sample preparation protocols remain significant hurdles. The application of mNGS across various systemic infections highlights its clinical utility. Case studies discussed in this review illustrate its efficacy in diagnosing respiratory tract infections, bloodstream infections, central nervous system infections, gastrointestinal infections, and others. By rapidly identifying pathogens and their genomic characteristics, mNGS facilitates timely and targeted therapeutic interventions, thereby improving patient outcomes and infection control measures. Looking ahead, the future of mNGS in infectious disease diagnostics appears promising. Advances in bioinformatics tools and sequencing technologies are anticipated to streamline data analysis, enhance sensitivity and specificity, and reduce turnaround times. Integration with clinical decision support systems promises to further optimize mNGS utilization in routine clinical practice. In conclusion, mNGS represents a paradigm shift in the field of infectious disease diagnostics, offering unparalleled insights into microbial diversity and pathogenesis. While challenges persist, ongoing technological advancements hold immense potential to consolidate mNGS as a pivotal tool in the armamentarium of modern medicine, empowering clinicians with precise, rapid, and comprehensive pathogen detection capabilities.


Fig. 1 (a) The basic principles of the Mendelian randomization (MR) study: (1) assumption 1: single-nucleotide polymorphisms (SNPs) are closely linked to blood biomarkers; (2) assumption 2: SNPs are not affected by confounders; and (3) assumption 3: SNPs must only affect acute pancreatitis (AP) through blood biomarkers. (b) A flowchart about the screening of instrumental variables (IVs) and how the MR analysis was performed. (c) The schematic diagram of multivariate MR (MVMR) analysis: (1) the three exposures should exhibit some form of interrelationship, such as the association between smoking, alcohol consumption, and other blood cell traits; (2) SNPs should demonstrate significant associations specifically with one of the exposures; (3) SNPs should be available and extracted for all exposures and outcomes without any missing information, ensuring comprehensive coverage across all variables; and (4) MVMR analysis necessitates the availability of complete genome-wide association study results for both the exposures and outcomes, enabling a thorough investigation of the relationships between the variables. BG, blood glucose; HLSR, high light scatter reticulocyte count; IVW, inverse variance weighted; LOO, leave-one-out; MR-PRESSO, Mendelian randomization pleiotropy residual sum and outlier; RBC, red blood cell.
Fig. 2 Forest plot of two-sample Mendelian randomization (MR) analysis to estimate causal effects between blood cell traits and acute pancreatitis in European populations (2018-2021) genome-wide association study summary statistics. The effect sizes were expressed as odds ratios (ORs) per SD increase in the quantitative exposure. The x-axis represents the OR value, and the y-axis represents the invalid line perpendicular to the x-axis. The error bars on the figures represent the 95% confidence interval (CI) for the estimated effects. P < 0.05 was used to determine statistical significance. Hb, hemoglobin concentration; HLSR, high light scatter reticulocyte count; HLSRPRC, high light scatter reticulocyte percentage of red cells; IFR, immature fraction of reticulocytes; IVW, inverse variance weighted; MCH, mean corpuscular hemoglobin; RBC, red blood cell; RCD, red cell distribution; RFRC, reticulocyte fraction of red cells; WBC, white blood cell.
Fig. 3 Forest plot of two-sample Mendelian randomization (MR) analysis to estimate causal effects between blood biomarkers and acute pancreatitis in European populations (2014-2022) genome-wide association study summary statistics. The effect sizes were expressed as odds ratios (ORs) per SD increase in the quantitative exposure. The x-axis represents the OR value, and the y-axis represents the invalid line perpendicular to the x-axis. The error bars on the figures represent the 95% confidence interval (CI) for the estimated effects. P < 0.05 was used to determine statistical significance. Alb, albumin; Ang-2, angiotensin II; AT-III, antithrombin III; BUN, blood urea nitrogen; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; IVW, inverse variance weighted; LDL, low-density lipoprotein; PCT, procalcitonin; PT, prothrombin time; SCr, serum creatinine; TC, total cholesterol level.
Large‐scale genome‐wide association studies identified causal relationship between multiple blood biomarkers and risk of acute pancreatitis

November 2024

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14 Reads

Journal of Gastroenterology and Hepatology

Background and Aim Observational studies have shown that there is a connection between blood biomarkers and the occurrence of acute pancreatitis (AP). Nevertheless, the causal relationships are still not clear. The purpose of this study was to evaluate causal association between biomarkers and AP. Method(s) A bidirectional two‐sample Mendelian randomization (MR) analysis was applied to investigate the causal association between blood biomarkers and AP. Summary statistics obtained from genome‐wide association studies were utilized for this analysis. The primary statistical approach employed was the inverse variance weighted (IVW) method, complemented by sensitivity analyses aimed at assessing heterogeneity and pleiotropy. Furthermore, a multivariable MR (MVMR) analysis was performed to adjust for confounders. Results A total of 11 red blood cell (RBC) traits, 6 white blood cell traits, platelet count, and 30 blood biomarkers were analyzed in this study. Genetically predicted RBC count (IVW odds ratio [OR] = 1.144, P = 0.004), the high light scatter reticulocyte count (HLSR) (OR = 1.127, P = 0.022), blood glucose (BG) (OR = 1.480, P = 0.019), and leptin (OR = 1.234, P = 0.050) were suggestively associated with an increased risk of AP. Reverse MR analysis showed no causal effect of AP on RBC, HLSR, BG, and leptin (IVW P > 0.05). Sensitivity analyses and MVMR analysis still supported the earlier causality. Conclusion(s) Our findings provide evidence of a suggestive association between RBC count, HLSR, BG, and leptin with an increased susceptibility to AP. These findings aid in our comprehension of the cause of AP and may be used as potential prognostic markers or predictors of severity with AP.


Clinical and pathological characteristics of patients
Univariate and multivariate Cox regression to explore the inuence of IVRFS
Univariate and multivariate Cox regression to explore the inuence of EURFS
Univariate and multivariate Cox regression to explore the inuence of RFS
Preoperative Serum Creatinine Levels as a Prognostic Indicator in Upper Urinary Tract Urothelial Carcinoma after Radical Nephroureterectomy: A Retrospective Clinical Study

October 2024

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14 Reads

Objective This study aimed to elucidate the prognostic significance of preoperative serum creatinine (SCr) levels on oncologic outcomes in patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UUT-UC). Methods We retrospectively analyzed clinical data from 227 patients treated for UUT-UC with RNU at Beijing Chaoyang Hospital, Capital Medical University between 2009 and 2020. Patients were stratified into groups based on optimal SCr thresholds identified via receiver operating characteristic (ROC) curve analysis. We compared baseline characteristics across these groups and assessed the impact of preoperative SCr on intravesical recurrence-free survival (IVRFS), extra-urinary recurrence-free survival (EURFS), recurrence-free survival (RFS), and overall survival (OS) using Kaplan-Meier survival plots and Cox proportional hazards regression models. Results Our cohort included 227 patients who fulfilled the study's inclusion and exclusion criteria. Pathologic T stage was identified as a predictor of IVRFS. Both pathologic T stage and preoperative SCr levels were significant predictors of EURFS and RFS. Additionally, age, pathologic T stage, neural invasion, and preoperative SCr were all significant prognostic factors for OS. Conclusion Elevated preoperative SCr levels are associated with poorer prognoses in patients with UUT-UC undergoing RNU, particularly impacting EURFS, RFS, and OS. Conversely, preoperative SCr levels did not correlate with IVR.


Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy

September 2024

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2 Reads

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2 Citations

World Journal of Gastrointestinal Surgery

BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged. AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma (dCCA) who underwent pancreatoduodenectomy (PD). METHODS This single-center study included 216 patients with dCCA after PD between January 1, 2011, and December 31, 2022. The individuals were categorized into two sets based on their systemic inflammatory response index (SIRI) levels: A low SIRI group (SIRI < 1.5, n = 123) and a high SIRI group (SIRI ≥ 1.5, n = 93). Inflammatory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves. Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival (OS) and recurrence-free survival (RFS). RESULTS The study included a total of 216 patients, with 58.3% being male and a mean age of 65.6 ± 9.6 years. 123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA. SIRI had an area under the curve value of 0.674 for diagnosing dCCA, showing better performance than other inflammatory biomarkers. Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD, leading to lower OS [hazard ratios (HR) = 1.868, P = 0.006] and RFS (HR = 0.949, P < 0.001). Additionally, survival analysis indicated a significantly better prognosis for patients in the low SIRI group (P < 0.001). CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.



The basal methylation pattern. (A) During very early embryogenesis (preimplantation), almost all DNAs are in an unmethylated state (blue boxes). During implantation, de novo methylation occurs causing the methylation (yellow boxes) of almost all CpG sites in the genome. CpG islands are protected from this process by cis‐acting sequences that are recognized by transcription factors in the early embryonic cells. (B) After implantation, cells lose their ability to methylate de novo, but the bimodal pattern is preserved through cell divisions by a maintenance mechanism. Me, methylation; TF, transcription factor.
The application status of cfDNA in non‐invasive diagnosis. cfDNA, cell‐free DNA.
The role of cell‐free DNA in non‐invasive diagnosis of urinary tract infection

Urinary tract infection (UTI) constitutes a pervasive health concern. UTIs are dichotomously classified into upper and lower strata, and further categorized as either complicated or uncomplicated. Upper UTIs predominantly afflict the renal and ureteral domains, typified by conditions exemplified in pyelonephritis, whereas lower UTIs manifest within the confines of the urethra and bladder. The conventional diagnosis of UTIs relies upon clinical manifestations and urine culture. Common symptoms encompass dysuria, frequent micturition, hematuria, and suprapubic discomfort. Urine culture serves to identify the specific pathogens instigating the infection and assess their antibiotic susceptibility. However, this procedural protocol generally necessitates an approximate duration of 24 h, coupled with an additional 24‐h interval for antibiotic susceptibility testing. In contradistinction, the detection of cell‐free DNA (cfDNA) in the circulatory system presents a potential avenue for non‐invasive diagnostic modalities. Notwithstanding, cfDNA emanates from deteriorating cells, affording insights into the extant cellular demise within the organism. Extensive scholarly inquiry has established a positive correlation between cfDNA concentration in the bloodstream and the incidence of cell death in conditions, such as severe traumas, sepsis, aseptic inflammation, myocardial infarction, and stroke. However, limited investigative effort has been devoted to elucidating the diagnostic potential of cfDNA in the context of UTIs. Consequently, the concentration and constitution of plasma cfDNA harbor substantial promise for non‐invasively diagnosing UTIs. In summation, the utilization of cfDNA in UTI diagnosis remains an incipient area of scholarly pursuit, underscoring the imperative for further research to elucidate the prospective role of plasma cfDNA in non‐intrusively discerning UTIs.


Factors Affecting Neutrophil Functions During Sepsis: Human Microbiome and Epigenetics

May 2024

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48 Reads

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1 Citation

Journal of Leukocyte Biology

Sepsis is a severe disease that occurs when the body's immune system reacts excessively to infection. The body's response, which includes an intense anti-bacterial reaction, can damage its tissues and organs. Neutrophils are the major components of white blood cells in circulation and play a vital role in innate immunity while fighting against infections, and are considered a feature determining sepsis classification. There's a plethora of basic research detailing neutrophil functioning, among which, the study of neutrophil extracellular traps (NETs) is providing novel insights into mechanisms and treatments of sepsis. This review explores their functions, dysfunctions, and influences in the context of sepsis. The interplay between neutrophils and the human microbiome and the impact of DNA methylation on neutrophil function in sepsis are crucial areas of study. The interaction between neutrophils and the human microbiome is complex, particularly in the context of sepsis where dysbiosis may occur. We highlight the importance of deciphering neutrophil’s functional alterations and their epigenetic features in sepsis because it is critical for defining sepsis endotypes and opening up the possibility for novel diagnostic methods and therapy. Specifically, epigenetic signatures are pivotal since they will provide a novel implication for sepsis diagnostic method when used in combination with the cell-free DNA (cfDNA). Research is exploring how specific patterns of DNA methylation in neutrophils, detectable in cfDNA, could serve as biomarkers for the early detection of sepsis.


Targeting vital metabolites as promising therapeutic targets via immunometabolism manipulation. Tumors are biased towards aerobic glycolysis in the TME. Macrophages produce ROS in addition to TNF-α and IL-1β. Subsequently, succinate accumulation stabilizes HIF-1α via the inhibition of PHD enzyme activity and the generation of IL-1β. Succinate accumulation results from TLR4 signaling and LPS-activated macrophages via glutamine metabolism. Itaconate is synthesized from cis-aconitate in the TCA cycle in macrophages, which is activated by LPS and other TRL ligands; these stimuli improve ACOD1, which then shifts cis-aconitate out of the TCA cycle to produce aconitate. TME, tumor microenvironment; ACOD1, aconitate decarboxylase 1; α-KG, α-ketoglutarate; DC, dendritic cell; HIF-1α, hypoxia-inducible factor-1 alpha; LPS, lipopolysaccharide; PHD, prolyl hydroxylase domain; ROS, reactive oxygen species; SDH, succinate dehydrogenase; TCA cycle, tricarboxylic acid cycle; TLR, toll-like receptor; TNF-α, tumor necrosis factor alpha; IL-1β, interleukin-1 beta.
Overview of carbohydrate, lipid, and protein metabolism by targeting central metabolites in HCC, IR injury, and rejection. ROS, reactive oxygen species; GSNOR, denitrosylating enzyme S-nitrosoglutathione reductase; αTOS, alpha-tocopheryl succinate; SDH, succinate dehydrogenase; YAP/TAZ, Yes-associated protein/transcriptional coactivator with PDZ-binding motif; VES, vitamin E succinate; IR injury, ischemia-reperfusion injury; ACOD1, aconitate decarboxylase 1; HCC, hepatocellular carcinoma; mTOR, the mammalian target of rapamycin; miRNA, microRNAs; SREBP-1, sterol regulatory element‐binding protein 1; FA, fatty acid; FAO, fatty acid oxidation; FATP, fatty acid transport protein; TAMs, tumor‐associated macrophages; IL-1β, interleukin-1 beta; NKs, natural killer cells; MCCC2, methylcrotonoyl-CoA carboxylase 2; DON, 6-diazo-5-oxo-L-norleucine; SLC27A5, the solute carrier family 27 member 5; ETC, electron transport chain; CPT2, carnitine palmitoyltransferase 2; 2-DG, 2-deoxy-D-glucose.
Therapeutically targeting essential metabolites to improve immunometabolism manipulation after liver transplantation for hepatocellular carcinoma

July 2023

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43 Reads

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2 Citations

Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy worldwide and is associated with a poor prognosis. Sophisticated molecular mechanisms and biological characteristics need to be explored to gain a better understanding of HCC. The role of metabolites in cancer immunometabolism has been widely recognized as a hallmark of cancer in the tumor microenvironment (TME). Recent studies have focused on metabolites that are derived from carbohydrate, lipid, and protein metabolism, because alterations in these may contribute to HCC progression, ischemia-reperfusion (IR) injury during liver transplantation (LT), and post-LT rejection. Immune cells play a central role in the HCC microenvironment and the duration of IR or rejection. They shape immune responses through metabolite modifications and by engaging in complex crosstalk with tumor cells. A growing number of publications suggest that immune cell functions in the TME are closely linked to metabolic changes. In this review, we summarize recent findings on the primary metabolites in the TME and post-LT metabolism and relate these studies to HCC development, IR injury, and post-LT rejection. Our understanding of aberrant metabolism and metabolite targeting based on regulatory metabolic pathways may provide a novel strategy to enhance immunometabolism manipulation by reprogramming cell metabolism.

Citations (2)


... Currently, the identification of pathogens mainly relies on conventional microbiological tests (CMTs), including culture, microscopic smears, polymerase chain reactions (PCR) and serologic testing. However, CMTs have certain limitations, such as time-consuming, complex operations, and low detection rates, especially for uncommon pathogens and difficult-to-culture organisms, making them inadequate to meet clinical needs (Rajapaksha et al., 2019;Zhao et al., 2024). With the continuous development of sequencing technology, the emergence of metagenomic next-generation sequencing (mNGS) has brought significant advancements in the field of infectious disease diagnosis, particularly in the area of pulmonary infections . ...

Reference:

Application of targeted next-generation sequencing for pathogens diagnosis and drug resistance prediction in bronchoalveolar lavage fluid of pulmonary infections
Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases

... Initially proposed in 2016, SIRI is calculated using the following formula: SIRI = neutrophil × monocyte/ lymphocyte (10). SIRI has demonstrated significant prognostic value in various cancers, including colorectal cancer (11), gastric cancer (12), cholangiocarcinoma (13), thyroid cancer (14), and non-small cell lung cancer (NSCLC) (15). Its prognostic value in patients with glioma has also been explored (16)(17)(18)(19)(20)(21)(22)(23)(24)(25); however, findings have been inconsistent. ...

Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy
  • Citing Article
  • September 2024

World Journal of Gastrointestinal Surgery