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Biomedical subjects

Shujun Li

Publications and source records attributed to Shujun Li.

10 recordsLinked to original sources

Unveiling the power of TIIC: A prognostic tool for esophageal adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EAC) remains a lethal malignancy with limited prognostic tools for guiding immunotherapy. Tumor-infiltrating immune cells (TIICs) play a critical role in EAC prognosis and treatment response. METHODS: We integrated single-cell RNA sequencing and bulk transcriptome data from TCGA and GEO databases. TIIC-specific RNAs were identified via tissue specificity index calculation combined with machine learning feature selection. Twenty machine learning algorithms were benchmarked to construct an optimal TIIC signature score (TIIC-Score) based on the comprehensive C-index. Immunotherapy response, genomic mutation, and copy number variation were analyzed. Summary-data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (MR) were performed to explore genetic associations. Core prognostic TIIC-related genes were functionally validated in esophageal cancer cell lines through loss-of-function assays. RESULTS: The TIIC-Score demonstrated robust prognostic value for 1-, 2-, and 3-year overall survival across multiple cohorts, outperforming 22 published models. High TIIC-Score was associated with poor survival and increased chromosomal instability. Mutation profiling revealed high frequencies of TP53 (78.2%), TTN (48.7%), and SYNE1 (30.8%). MR analysis identified a significant association between gastro-oesophageal reflux and EAC risk at SNP rs8130507. Functionally, CCNI was upregulated in esophageal cancer cells, and its knockdown suppressed malignant phenotypes while promoting apoptosis, supporting its pro-tumorigenic role. CONCLUSION: The TIIC-Score provides a novel prognostic framework for EAC that effectively stratifies patient risk and may help identify individuals most likely to benefit from immunotherapy.

Esophageal adenocarcinoma↗

Clinical impact of metagenomic next-generation sequencing for pathogen identification and guided therapy in pediatric intensive care unit patients with severe pulmonary infections.

UNLABELLED: To explore the diagnostic efficiency, clinical concordance, and precision treatment value of metagenomic next-generation sequencing (mNGS) for severe pulmonary infections in children in the pediatric intensive care unit (PICU), and to provide evidence for improving microbiological diagnosis and optimizing anti-infective strategies. A retrospective cohort study included 89 children with severe pneumonia in the PICU in 2024. All underwent routine microbiological testing and mNGS of bronchoalveolar lavage fluid (BALF). Detection rates, pathogen composition, co-infection identification, diagnostic concordance, and treatment impact were analyzed. Metagenomic next-generation sequencing demonstrated high diagnostic sensitivity in the PICU setting, achieving a positive detection rate of 90.0% (80/89) and identifying a diverse spectrum of 103 pathogens, including 50.5% viruses, 43.7% bacteria, 38.8% co-infections (vs 11.6%), and 86.3% diagnostic concordance (vs 55.8%, P < 0.01). Among 46 patients included in the therapeutic outcome analysis (22 in the mNGS-guided group), 21 patients in the mNGS-guided group improved. Multivariate logistic regression analysis, adjusting for confounding factors (age, underlying diseases, PaO2/FiO2 ratio, PRISM III score, and preoperative antibiotic use duration), confirmed that mNGS-guided therapy was an independent protective factor for achieving the primary outcome (OR = 5.23, 95% CI: 1.87-14.61, P = 0.002) and secondary outcomes (C-reactive protein reduction &#x2265;50%: OR = 4.89, 95% CI: 1.72-13.93, P = 0.003; oxygenation improvement: OR = 5.67, 95% CI: 1.98-16.21, P = 0.001). Metagenomic next-generation sequencing demonstrated high diagnostic sensitivity in the PICU setting, guiding precision therapy, and improving prognosis. IMPORTANCE: It supports metagenomic next-generation sequencing (mNGS) as a supplementary tool for pediatric intensive care unit (PICU) refractory infections, guides anti-infective adjustments, and informs tiered diagnostic pathways for resource-limited settings to optimize cost-effectiveness.

Humans↗

Analysis of security problems in a medical image encryption system.

Recently, a new system for the secure transmission and efficient storage of medical images interleaved with patient information has been proposed in 2003 by Rajendra Acharya et al. In this paper, we analyse the security of this system, showing how to improve it to obtain a truly secure system.

Algorithms↗

Solution structure of Kti11p from Saccharomyces cerevisiae reveals a novel zinc-binding module.

Kti11p is a small, highly conserved CSL zinc finger-containing protein found in many eukaryotes. It was first identified as one of the factors required for maintaining the sensitivity of Saccharomyces cerevisiae to Kluyveromyces lactis zymocin. Then, it was found to be identical to Dph3, a protein required for diphthamide biosynthesis on eEF-2, the target of diphtheria toxin and Pseudomonas exotoxin A, in both yeast and higher eukaryotes. Furthermore, Kti11p/Dph3 was found to physically interact with core-Elongator, ribosomal proteins, eEF-2, two other proteins required for diphthamide modification on eEF-2, and DelGEF. Here, we determined the solution structure of Kti11p using NMR, providing the first structure of the CSL-class zinc-binding protein family. We present the first experimental evidence that Kti11p can bind a single Zn(2+) ion by its four conserved cysteine residues. The major structure of Kti11p comprises a beta sandwich as well as an alpha helix. Moreover, a structure-based similarity search suggests that it represents a novel structure and may define a new family of the zinc ribbon fold group. Therefore, our work provides a molecular basis for further understanding the multiple functions of Kti11p/Dph3 in different biological processes.

Amino Acid Sequence↗

Extrarenal ETB plays a significant role in controlling cardiovascular responses to high dietary sodium in rats.

Endothelin-B receptor (ET(B))-deficient rats have low-renin, salt-sensitive hypertension. We hypothesized this was caused by an absence of renal ET(B) signaling and performed a series of experiments to examine the effect of dietary sodium (Na) on endothelin-1 (ET1) expression and renal function in wild-type (WT) and ET(B)-deficient rats. We found that ET(B) deficiency, but not dietary Na, increases circulating and tissue (kidney and aorta) ET1 levels. Quantitative reverse-transcription polymerase chain reaction reveals that aortic and renal ET1 and endothelin-A receptor (ET(A)) mRNA, however, are similarly increased by dietary Na in ET(B)-WT and ET(B)-deficient rats. We then determined the effect of chronic ET(A) blockade on blood pressure (direct conscious measurements), urinary protein excretion, and creatinine clearance (Crcl). On a Na-deficient diet, ET(B)-deficient rats have mild proteinuria and impaired Crcl. On a high-Na diet, severe hypertension and renal dysfunction develop in ET(B)-deficient rats. Chronic ET(A) blockade prevents hypertension and renal injury. To determine the role of the renal versus the extrarenal endothelin system, we performed renal cross-transplantation. We found that ET(B) deficiency in the body is associated with renal injury and an impaired ability to excrete an Na load. We also found that ET(B) deficiency in the body affects blood pressure response to dietary Na. Expression of ET1 and ET(A) are regulated by dietary Na. ET(B) receptors outside of the kidney, likely by functioning as a clearance receptor for ET1, limit salt-sensitivity in rats.

Animals↗

Breaking a chaos-noise-based secure communication scheme.

This paper studies the security of a secure communication scheme based on two discrete-time intermittently chaotic systems synchronized via a common random driving signal. Some security defects of the scheme are revealed: 1) The key space can be remarkably reduced; 2) the decryption is insensitive to the mismatch of the secret key; 3) the key-generation process is insecure against known/chosen-plaintext attacks. The first two defects mean that the scheme is not secure enough against brute-force attacks, and the third one means that an attacker can easily break the cryptosystem by approximately estimating the secret key once he has a chance to access a fragment of the generated keystream. Yet it remains to be clarified if intermittent chaos could be used for designing secure chaotic cryptosystems.

Algorithms↗

Investigation of zinc-containing peptide deformylase from Leptospira interrogans by X-ray absorption near-edge spectroscopy.

Peptide deformylase (PDF, EC 3.5.1.27) is essential for the normal growth of eubacterium but not for mammalians. Recently, PDF has been studied as a target for new antibiotics. Its activity is strongly dependent on the bound metal ion. The crystallographic studies did not show any significant structural difference upon various bound metal ions. In this paper, X-ray absorption spectroscopy was employed to determine the local structure around the zinc ion of PDF from Leptospira interrogans in dry powder. XANES (X-ray absorption near-edge structure) calculations were performed and the local geometry of the active center was reconstructed successfully. By comparing with the crystal structure of an enzyme-product complex, the results from calculations show that a water molecule has moved towards the zinc ion and lies in the distance range to coordinate with the zinc ion weakly.

Amidohydrolases↗

PH domain of G protein-coupled receptor kinase-2 binds to protein kinase C (PKC) and negatively regulates activity of PKC kinase.

G protein-coupled receptor kinase-2 (GRK),also known as beta1-adrenergic receptor kinase(beta-ARK1), plays an important role in agonist-induced desensitization of the beta-adrenergic receptors. Activation of protein kinase C (PKC) is able to stimulate phosphorylation and activation of GRKs and induce desensitization of G protein-coupled receptor. However, detail mechanism of interaction between PKC and GRK2 and the effect of GRK2 on activity of PKC remain unknown. Pleckstrin homology (PH) domain is a kind of functionally domain containing about 120 amino acids, which exists on many protein molecules that involve in cellular signal transduction. A PH domain located in GRK2 residue 548 to 660 may play a significant role in mediating interaction between PKC and GRK2. In present study, we revealed that PKC could associate with PH domain of GRK2 in pull-down assay in vitro. Co-immunoprecipitation displayed binding of PKC to GRK2 in intact Jurkat cells after prolonged stimulation of epinephrine. Assay of PKC beta1 kinase activity indicated that the binding of the PH domain of GRK2 to PKC beta 1 could down-regulate activity of PKC beta 1 kinase. Thus, GRK2 may play a negative feedback regulatory role on PKCbeta1 activity in interaction between GRK2 and PKCbeta 1.

Agammaglobulinaemia Tyrosine Kinase↗

Laparoscopic donor nephrectomy at a low volume living donor transplant center: successful outcomes can be expected.

PURPOSE: Concern has been raised about possible increased morbidity associated with laparoscopic donor nephrectomy (LDN) during the learning curve of the procedure and at centers with a low volume of living donors. We evaluated the safety and success of LDN at a low volume living donor transplant center with a skilled laparoscopic urologist and experienced renal transplant team. MATERIALS AND METHODS: We reviewed the records of all patients who underwent LDN at our institution. A single surgeon skilled in laparoscopy (JAC) performed all LDNs. Patient demographics, operative reports, complications and recipient outcomes were evaluated. RESULTS: A total of 17 LDNs were performed between January 2000 and September 2002. There was 1 elective conversion to an open procedure for kidney harvest due to complex hilar anatomy. Only 1 minor complication occurred (wound seroma) and 1 donor had creatinine persistently elevated to 1.9 mg/dl (normal 0.6 to 1.2). Mean operating room time, estimated blood loss and hospital stay were 250 minutes, 188 ml and 2.5 days, respectively. Recipient creatinine had a nadir mean of 1.2 mg/dl and a 90-day postoperative mean of 1.6 mg/dl. One recipient eventually lost the graft due to recurrent disease. CONCLUSIONS: LDN can be performed safely and efficiently at low volume transplant centers with a skilled laparoscopist and experienced renal transplant team. Laparoscopic skills developed during similar procedures, such as laparoscopic radical and partial nephrectomy, minimize the learning curve and morbidity of LDN to produce results consistent with those in the published literature.

Adult↗

Do preoperative finger pressures predict early arterial steal in hemodialysis access patients? A prospective analysis.

BACKGROUND: Hand ischemia resulting from arterial steal is a serious complication in patients undergoing hemodialysis access, but specific risk factors for steal remain in dispute. The purpose of this study was to determine whether plethysmographically derived finger pressures (FPs) or digital-brachial indices (DBIs) are predictive of symptomatic arterial steal. METHODS: We prospectively studied 72 patients (37 men, 35 women; mean age, 57 +/- 10 years) who were undergoing brachial artery-based hemodialysis access. All patients had complete pre- and postoperative hand examinations and FP determinations. Surgeons were blinded to preoperative FP results. RESULTS: Prosthetic graft was used in 60 patients (6-mm polytetrafluoroethylene [PTFE] in 50, tapered PTFE in 10), and brachial-based arteriovenous fistulas were created in 12. Fourteen (19%) patients developed arterial steal symptoms. The mean preoperative FP was significantly lower in steal patients than in those without steal (131 +/- 27 vs 151 +/- 31 mm Hg, P <.03). Nine (64%) of the patients with steal had DBIs <1.0, compared to 18 (31%) of the patients without steal (P =.02). However, there was no absolute FP or DBI threshold below which steal was inevitable. The occurrence of steal was attributed to proximal arterial stenoses in seven, to distal arterial disease in five, and was unknown in two. When comparing the 14 patients who developed steal to the 58 who did not, we noted that a higher proportion of steal patients had coronary artery disease (57% vs 17%, P =.005). Steal was more likely to develop in patients with arteriovenous fistulas than in patients with prosthetic grafts (43% vs 14%, P =.009). There were no significant differences in demographic factors, atherosclerotic risks (diabetes, smoking, hypertension, dyslipidemia), prevalence of peripheral vascular disease, cerebrovascular disease, shunt location, tapered vs straight graft, or number of prior grafts placed. CONCLUSIONS: These data indicate that preoperative FPs are lower in patients who develop steal syndrome after hemodialysis access. Patients with preoperative DBIs <1.0 are more likely to develop steal, but there is no DBI threshold below which steal is inevitable. Steal is more likely in patients undergoing brachial-based arteriovenous fistulas than in those receiving prosthetic grafts.

Aged↗