A Case of Pseudoelevation of Prostate Specific Antigen Level.

BACKGROUND: Prostate specific antigen (PSA) is an important marker for the diagnosis, monitoring and efficacy evaluation of prostate cancer. Therefore, the accuracy of PSA detection results is of great significance for the diagnosis and treatment of prostate cancer. METHODS: We reported a case with abnormally elevated PSA. The patient's serum samples were subjected to investigations for suspected interference. Interference studies included measurement of PSA on different analytical platforms, serial dilutions, heterophilic blocking tube (HBT) analysis and polyethylene glycol (PEG) precipitation. RESULTS: In this case, the abnormal increases in the results of PSA detected by Abbott i2000SR immune analyzer were considered to be the pseudoelevation caused by interferences, resulting in unnecessary prostate puncture examination. CONCLUSIONS: When the patient's PSA level is abnormally elevated, which is not consistent with the clinical diagnosis, we should consider immunological interference in PSA assays. Pretreatment with PEG may be an economical, simple, and feasible scheme for removing interference.

A case of Pseudo-Lowering of Blood Routine Results caused by Improper Blood Collection Operation.

BACKGROUND: Unqualified samples directly affect the accuracy of laboratory test results. Some links in the preanalysis stage are prone to produce unqualified samples that are difficult to identify, leading to inaccurate test results and affecting clinical diagnosis and treatment. METHODS: This paper reports a case of pseudo-lowering of blood routine results caused by improper blood collection operation. RESULTS: The blood routine samples caused by improper blood collection operation by nurses were diluted by the sealing solution of the indwelling needle, which resulted in inaccurate test results. CONCLUSIONS: The laboratory should pay attention to the quality control in the preanalysis stage and identify unqualified samples in time, provide reliable diagnostic basis for clinical practice, and avoid the occurrence of adverse events.

Efficacy and Mechanism of Core Traditional Chinese Medicines for Treating Malignant Lymphoma based on Efficacy Studies: A Study Supported by Network Pharmacology and Molecular Docking.

BACKGROUND: The burden of malignant lymphoma in China is greater than the global equivalent. The randomized controlled trials provide medical evidence that TCM can improve the response and survival in patients with lymphoma. However, the mechanisms underlying remain undefined. OBJECTIVE: Evidence-based data mining for traditional Chinese medicine (TCM) on improving response and survival in malignant lymphoma treatment was performed in this study. In addition, the mechanisms of TCM through network pharmacology and molecular docking were explored. METHODS: The China national knowledge infrastructure, Wanfang Data, China Science and Technology Journal Database, PubMed, and Web of Science databases were searched to select TCM formulas with response and survival benefits in the treatment of malignant lymphomas. We then analyzed and visualized the tropism of taste, frequency of drug use, dosage, clustering, association rules mining (minimum support threshold as 0.20, the minimum confidence threshold as 0.80 and lift >1), and complex networks for potential core herb compositions using Excel, IBM SPSS Statistics 26, and IBM SPSS Modeler 18. TCM systems pharmacology, GeneCards, Online Mendelian Inheritance in Man, and other databases were used to screen potential core active ingredients and malignant lymphoma-related targets. The intersection targets were used to construct a protein interaction network using Cytoscape to obtain the key targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were used to analyze the core target, and molecular docking of key components and targets was performed using CB-Dock2. RESULTS: Twenty-four Chinese herbal formulae were included, encompassing 107 herbs with mainly cold and warm properties and bitter and sweet flavors. They were associated with the yin meridians of the liver, spleen, and lungs. The TCMs underwent association rule analysis, identified 27 association rules, including 12 herb pairs and 13 angle medicine, and clustered into eight classes by clustering analysis. Combined with the results from mining analysis, Pinelliae (Ban-xia), Poria (Fu-ling), Atractylodis macrocephalae (Bai-zhu), Curcumae (E-zhu), and Sparganii (San-leng) were the potential core herbs According to network pharmacology and molecular docking, the main core components of the potential core drugs are hederagenin, cerevisterol, 14- acetyl-12-senecioyl-2E,8E,10E-atractylentriol, 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid, cavidine, and baicalein. These core drugs are mainly involved in the pathways of EGFR tyrosine kinase inhibitor resistance, PD-1/L1, natural killer cell-mediated cytotoxicity, NF-κB, epithelial cell signaling in H. pylori infections, and Th17 cell differentiation. They aid in regulating the transmembrane receptor protein tyrosine kinase signaling pathway, ERBB signaling pathway, PI3K signaling pathway, and phosphorylation process. Ten key components and eight key targets, including baicalein and hederagenin, demonstrated strong binding activity. CONCLUSION: Collectively, some core herbs exerted anti-tumor effects through immune and inflammatory pathway modulation, inhibition of immune escape, and induction of cell apoptosis. These findings support future evidence-based research on malignant lymphoma treatment using TCM.

Stratifin promotes the growth and proliferation of hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the second leading cancer cause of death worldwide. SFN plays a vital role in some malignancies. The purpose of this study was to investigate the role of SFN in the development of HCC. METHODS: The bioinformatics database was used to detect the expression of SFN and its prognosis in HCC patients. And the protein-protein interaction network was established. IHC and Elisa were used to analyze the expression level and clinical characteristics of SFN in HCC patients. Subsequently, siRNA knockdown of SFN expression in HCC cell lines was used to explore whether SFN could promote the development of HCC. RESULTS: SFN was highly expressed in the tissues and serum of hepatocellular carcinoma, and its expression level was correlated with the tumor which was single or not in patients. Bioanalysis and histochemistry results showed that CDC25B was co-expressed with SFN in HCC, which may be the upstream and downstream signaling molecule of SFN. Knockdown of SFN can inhibit cell proliferation, migration, invasion and promote apoptosis. CONCLUSIONS: Our results suggest that SFN may play an important role in HCC progression and may interact with CDC25B to promote malignant progression of HCC, providing a molecular target for future HCC therapy.

PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize.

BACKGROUND: Lung cancer is a serious threat to human life. It is of great significance to elucidate the pathogenesis of lung cancer and search for new markers. This study evaluate the clinical value of pyrroline-5-carboxylate reductase 1 (PYCR1) and explore its role and mechanisms in the malignant progression of lung cancer. METHODS: PYCR1 expression and its relationship with prognosis were analyzed using a bioinformatics database. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were utilized to examine the expression of PYCR1 in lung cancer tissues and peripheral blood. PYCR1-overexpressing lung cancer cells were constructed, then the cell proliferative, migration, and invasion ability was examined by the MTT and Transwell assays. siRNA against PRODH and STAT3 inhibitor sttatic was used to further elucidate the underlying mechanisms. Luciferase and CHIP assays were carried out for validate the how PYCR1 regulated PD-L1 expression via STAT3. Xenograft experiment was performed to determine the role of PYCR1 in vivo. RESULTS: Database analysis showed that PYCR1 expression was significantly increased in lung cancer tissues, and its high expression predicted poor prognosis. Lung cancer tissue and peripheral blood of patients showed obviously increased PYCR1 expression, and the sensitivity and specificity of serum PYCR1 in the diagnosis of lung cancer were 75.7% and 60%, respectively. PYCR1 overexpression enhanced the proliferative, migration, and invasion abilities of lung cancer cells. Both PRODH silence and stattic effectively attenuated the function of PYCR1. Animal experiment and IHC data indicated that PYCR1 could activated STAT3 phosphorylation and PD-L1, as well as suppressed T cell infiltration in lung cancer. Finally, we also validated that PYCR1 promoted PD-L1 transcription by elevating STAT3 binding to the gene promoter. CONCLUSION: PYCR1 has certain value in the diagnosis and prognosis of lung cancer. Moreover, through regulating JAK-STAT3 signaling pathway, PYCR1 significantly participated in process of lung cancer progression via the metabolism link between proline and glutamine, indicating that PYCR1 might be also a novel therapeutic target.

The thiol-sulfoxonium ylide photo-click reaction for bioconjugation.

Visible-light-mediated methods were heavily studied as a useful tool for cysteine-selective bio-conjugation; however, many current methods suffer from bio-incompatible reaction conditions and slow kinetics. To address these challenges, herein, we report a transition metal-free thiol-sulfoxonium ylide photo-click reaction that enables bioconjugation under bio-compatible conditions. The reaction is highly cysteine-selective and generally finished within minutes with naturally occurring riboflavin derivatives as organic photocatalysts. The catalysts and substrates are readily accessible and bench stable and have satisfactory water solubility. As a proof-of-concept study, the reaction was smoothly applied in chemo-proteomic analysis, which provides efficient tools to explore the druggable content of the human proteome.

Identification of an autoinhibitory, mitophagy-inducing peptide derived from the transmembrane domain of USP30.

The mitochondrial-anchored deubiquitinating enzyme USP30 (ubiquitin specific peptidase 30) antagonizes PRKN/parkin-mediated mitophagy, making it a potential target for treating Parkinson disease. However, few inhibitors targeting USP30 have been reported. Here, we report a novel peptide (Q14) derived from the transmembrane (TM) domain of USP30 that can target mitochondrial-anchored USP30 directly and increase mitophagy through two intriguing and distinct mechanisms: a novel autoinhibition mechanism in USP30 and accelerated autophagosome formation via the LC3-interacting region (LIR) of the Q14 peptide. We identified the potential binding sites between the Q14 peptide and USP30 and postulated that an allosteric autoinhibition mechanism regulates USP30 activity. Furthermore, the LIR motif in the Q14 peptide offers additional binding with LC3 and accelerated autophagosome formation. The two mechanisms synergistically enhance mitophagy. Our work provides novel insight and direction to the design of inhibitors for USP30 or other deubiquitinating enzymes (DUBs).Abbreviations: 3-MA: 3-methyladenine; ATTEC: autophagosome-tethering compound; BafA1: bafilomycin A1; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DMSO: dimethyl sulfoxide; FP: fluorescence polarization; FUNDC1: FUN14 domain containing 1; HCQ: hydroxychloroquine; LIR: LC3-interacting region; MST: microscale thermophoresis; mtDNA: mitochondrial DNA; mtPA-GFP: mitochondria-targeted photoactive fluorescence protein; OMM: outer mitochondrial membrane; PINK1: PTEN induced kinase 1; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; Rap: rapamycin; SA: streptavidin; TM: transmembrane; Ub: ubiquitin; Ub-AMC: Ub-7-amido-4-methylcoumarin; UPS: ubiquitin-protease system; USP: ubiquitin specific peptidase; USP30: ubiquitin specific peptidase 30.

Sulfonium-Driven Neoantigen-Released DNA Nanodevice as a Precise Vaccine for Tumor Immunotherapy and Prevention.

Peptide-based neoantigen vaccines hold tremendous potential for personalized tumor immunotherapy. However, effective delivery and controllable release of antigen peptides remain major challenges in stimulating robust and sustained immune responses. Programmable DNA nanodevices provide accurate fixed positions for antigens, which are convenient for the calculation of clinical dosage, and hold great potential as precise carriers. Here, a peptide-nucleic acid conjugate was prepared, which was driven by a propargyl sulfonium-based efficient and reversible bio-orthogonal reaction under weakly alkaline conditions, and folded into regular DNA nanodevice vaccines. The well-defined nanoplatform not only exhibits outstanding stability in serum, satisfactory safety, and effective internalization by antigen-presenting cells (RAW264.7 and BMDCs) but also obviously enhances cytokine (TNF-α, IL-6, and IL-12) secretion for further immune response. In vivo, the nanovaccine cooperating with OVA model antigens and CpG adjuvants stimulated an antigen-specific CD8+T cell response, significantly preventing the lung metastases of melanoma. In the B16-OVA tumor-bearing model, the growth inhibition rate of melanoma reached up to 50%. Similarly, the DNA nanodevice with neoantigen induced up to a maximum degree of complete MC-38 tumor regression in 80% of mice, possibly owing to antigen peptide reversible release driven by sulfonium and further cross-presentation. In brief, this study demonstrates that DNA nanodevices with sulfonium centers can provide a precise, biocompatible, and effective co-delivery vaccine platform for tumor immunotherapy and prevention.

miR-340 Exerts Suppressive Effect on Retinoblastoma Progression by Targeting KIF14.

Purpose: This work aimed to investigate the influences of microRNA-340 (miR-340) on proliferation and apoptosis of retinoblastoma (RB) cells and explore its regulatory mechanism. MATERIALS AND METHODS: miR-340 mimic and inhibitor were applied for up-regulating or inhibiting the expression of miR-340 in RB cell lines. Then, CCK-8 and AnnexinV-FITC/PI staining were used to measure cell proliferation and apoptosis, respectively. After that, luciferase assay was performed to affirm the direct targets of miR-340. Furthermore, qRT-PCR and western blotting assay were carried out to detect the levels of miR-340 and KIF14. RESULTS: Our results indicated that the miR-340 was lowly expressed in RB cell lines, and up-regulation of miR-340 can decrease the proliferation and induce the apoptosis of RB cells. Moreover, we verified that miR-340 controls KIF14 expression, either directly or through a subsequent molecular cascade, and inversely related to its expression. The results obtained from the rescue assays presented that over-expression of KIF14 reversed the miR-340-mediated inhibition on malignant phenotype of RB cells. CONCLUSIONS: Overall, we proved that miR-340 can decrease the proliferation and increase the apoptosis of RB cells, and its function in RB cells was at least partially achieved via down-regulation of KIF14, prompting that miR-340 was expected to supply a new direction for clinical therapy of RB in the future.

Remote real-time control of aerosol continuous monitoring for high radon concentration environments.

In this study, we developed a new continuous aerosol monitoring device, which can be controlled by a remote server and transmit data over the Internet according to the TCP protocol. The user can remotely control the device and obtain the data measured in real time, which can be used to send alarms related to the concentrations of radioactive aerosols. This new device was applied to remotely measuring the concentrations of nuclides (uranium, plutonium, and beta) in radioactive aerosols and for reducing the effects of high radon in the environment based on the measurements. The experimental results demonstrated that this novel device can provide accurate test results and transmit the results to the administrator's location, and it can be remotely controlled in order to remain at a safe distance away from a dangerous measurement area.

Design of a new comprehensive continuous monitoring system for environmental radioactive aerosol.

In order to comprehensive monitoring the radioactive isotopes from nuclear facilities, we developed a dual channel spectral monitoring instrument, and realized synchronous measurement for alpha, beta and gamma radionuclides. This article focuses on how to ensure its accuracy, stability and efficiency. First is the accuracy. In order to lower the interference of environmental and detector performance variation, the zero phase shift filter was designed to ensure the accuracy of characteristic peak position. Lorenz fitting algorithm was designed to reduce the effect of spectral low-energy tailing. Multi thread processing was introduced to ensure that there was sufficient time to complete our complex algorithms. Second is the stability. The complicated measuring process was decomposed into several sub-states. A state monitoring method was set up to timely dispose the abnormal operation. Third is the efficiency. Sampling process and measurement process were designed in synchronous to save monitoring time, which is especially useful for environmental low level radioactive monitoring. Continuous test for seven days shows that the detection limit is less than 0.0003Bq/m3 for U, 239Pu, and less than 0.048Bq/m3 for beta and 137Cs.