Inverted Sandwich-Type e-LCR Aided by Lambda Exonuclease-RecJf Combination Enables Ultrasensitive Detection of Low-Frequency EGFR-L858R Mutation in NSCLC.

Highly sensitive detection of low-frequency EGFR-L858R mutation is particularly important in guiding targeted therapy of nonsmall-cell lung carcinoma (NSCLC). To this end, a ligase chain reaction (LCR)-based electrochemical biosensor (e-LCR) with an inverted sandwich-type architecture was provided by combining a cooperation of lambda exonuclease-RecJf exonuclease (λ-RecJf exo). In this work, by designing a knife-like DNA substrate (an overhang ssDNA part referred to the "knife arm") and introducing the λ-RecJf exo, the unreacted DNA probes in the LCR were specially degraded while only the ligated products were preserved, after which the ligated knife-like DNA products were hybridized with capture probes on the gold electrode surface through the "knife arms", forming the inverted sandwich-type DNA structure and bringing the methylene blue-label close to the electrode surface to engender the electrical signal. Finally, the sensitivity of the e-LCR could be improved by 3 orders of magnitude with the help of the λ-RecJf exo, and due to the mutation recognizing in the ligation site of the employed ligase, this method could detect EGFR-L858R mutation down to 0.01%, along with a linear range of 1 fM-10 pM and a limit detection of 0.8 fM. Further, the developed method could distinguish between L858R positive and negative mutations in cultured cell samples, tumor tissue samples, and plasma samples, whose accuracy was verified by the droplet digital PCR, holding a huge potential in liquid biopsy for precisely guiding individualized-treatment of NSCLC patients with advantages of high sensitivity, low cost, and adaptability to point-of-care testing.

Scutellaria barbata D.Don and Scleromitrion diffusum (Willd.) R.J.Wang inhibits the progression of triple negative breast cancer though the activation inhibition of NF-κB triggered by CAFs-derived IL6.

ETHNOPHARMACOLOGICAL RELEVANCE: The treatment options for triple-negative breast cancer (TNBC) are limited. Traditional Chinese Medicine (TCM) plays an important role in the treatment of TNBC. The herb pair Scutellaria barbata D.Don and Scleromitrion diffusum (Willd.) R.J.Wang (SH) is commonly used in clinical practice for its anti-tumor properties. It has been proven to have good therapeutic effects on tumor-related diseases, but the underlying molecular mechanisms are not yet fully explained. AIM OF STUDY: Through bioinformatics, it was validated that IL6, primarily derived from cancer-associated fibroblasts (CAFs), is associated with poor prognosis. Additionally, cell and animal experiments confirmed that SH inhibits tumor proliferation, migration, and growth in an orthotopic tumor model by suppressing the IL6/NF-κB pathway. MATERIALS AND METHODS: GEO, TCGA and HPA databases were used to analyze the prognostic value of CAFs and IL6, then IL6 resource was detected. After the bioinformatics, the influence of CAFs and CAFs-derived IL6 on TNBC was verified by experiments both in vitro and in vivo. Cell clone formation assay, wound-Healing assay, and Transwell assay were used to detect the promotion of CAFs and CAFs-derived IL6 and the inhibition of SH in vitro. TNBC model in mice was used to prove the promotion of CAFs and CAFs-derived IL6 and the inhibition of SH in vivo. The biological pathway of NF-κB was explored by western blotting through detecting unique molecules. RESULTS: Bioinformatics analysis revealed that higher proportion of CAFs and elevated level of IL6 were significantly associated with poor prognosis in TNBC. At the same time, IL6 was proved predominantly derived from CAFs. After the indication of bioinformatics, experiments in vitro demonstrated that both CAFs and IL6 could enhance the clone formation and migration ability of MDA-MD-231 cells (231), furthermore, the promotion of CAFs was related with the level of IL6. Based on these data, mechanism was detected that CAFs-derived IL6 enhancement was closely related to the activation of NF-κB signaling pathway, while the activation can be reduced by SH. In the end, the promotion of CAFs/CAFs-derived IL6/NF-κB and the efficacy of SH inhibition were both confirmed by experiments in vivo. CONCLUSIONS: Bioinformatics data indicates that higher proportion of CAFs and higher level of CAFs-derived IL6 are significantly related to poorer survival of TNBC. CAFs and CAFs-derived IL6 were proved to promote the progression of TNBC both in vitro and in vivo, and the process of which was significantly related to the activation of NF-κB. SH inhibited the progress of TNBC, which was proved to be closely related to CAFs/CAFs-derived IL6/NF-κB.

Reagent-free anti-fouling electrochemical immunosensor based on AL-BSA/AuNPs/PANI coating for the point-of-care detection of C-reactive protein in plasma and whole blood.

Developing the portable CRP detection technologies that are suitable for point-of-care (POC) and primary care management is of utmost importance, and advancing the electrochemical immunosensors hold promise for POC implementation. Nevertheless, non-specific adsorption of numerous interfering proteins in complex biological media contaminates immunosensors, thereby restricting the reliability in detection efficacy. In this study, a three-dimensional flower-leaf shape amyloid bovine serum albumin/gold nanoparticles/polyaniline (AL-BSA/AuNPs/PANI) coating on the surface of the electrode was developed, which demonstrated strong anti-adsorption properties against bovine serum albumin, plasma, and cells. The immunosensor exhibited a good linear relationship to CRP response, featuring a detection limit of 0.09 µg/mL, consistent with clinical reference range. In addition, the CRP immunosensor demonstrated excellent specificity in other inflammation-related proteins and commendable anti-interference performance for CRP detection in plasma and whole blood tests. Importantly, by combining the development of a USB flash disk-type portable electrochemical workstation with a reagent-free mode, the developed CRP electrochemical immunosensor delivered ideal results in clinical samples. The anti-fouling performance, sensitivity and specificity of the immunosensor, as well as its flexible test modes in clinical samples, provide important scientific basis for developing POC detection technologies of vital biomarkers in complex biological media.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Serological response and immune-related adverse events following COVID-19 vaccination in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

With the popularity of Coronavirus disease 2019 (COVID-19) vaccine and the development of vaccination strategies, the impact of COVID-19 vaccine on cancer patients receiving immune checkpoint inhibitors (ICIs) is still unclear. In the systematic review and meta-analysis of patients with ICIs, we assessed the serological response of cancer patients receiving COVID-19 vaccine, and explored the risk of immune related adverse events (irAEs). We searched PubMed, EMBASE and Cochrane Library as of 10 June 2023, and included cancer patients who received ICIs and COVID-19 vaccine. The systematic review and meta-analysis include cohort study, cross-sectional study and case report. The outcome included the serological response, Spike-specific T-cell response, irAEs and rare adverse events. When possible, the data were analysed by random effect analysis, and the statistical heterogeneity was assessed by Q-test and I2 statistics. We explored the sources of heterogeneity through L'Abbe plots, Galbraith radial plots, and sensitivity analysis. The publication bias was evaluated by Egger's, Begg's linear regression test and funnel plot, and the impact of publication bias was further analysed by trim and fill method. 27 studies were eligible (19 cohort studies, 1 cross-sectional study and 7 case reports), involving 8331 patients (with 4724 receiving ICIs). Most studies used mRNA vaccine (BNT162b2 or mRNA-1273). Compared with cancer patients receiving chemotherapy, cancer patients receiving ICIs were significantly more likely to have seroconversion (RR = 1.05, 95%CI 1.01-1.10, P = 0.02). There were no statistically significant differences in seroconversion rates when comparing cancer patients receiving ICIs with controls without cancer (RR = 0.95, 95% CI 0.89-1.01, P = 0.09) or with cancer patients receiving targeted therapy (RR = 1.05, 95% CI 0.79-1.39, P = 0.75). The incidence of irAEs in patients receiving ICIs before and after COVID-19 vaccination was (21.96%, 95%CI 16.66%-28.94%) and (14.88%, 95%CI 8.65%-25.57%), respectively. The most common irAEs were endocrine abnormalities, skin disorders, etc. The certainty of evidence was low in cancer patients with ICIs, compared with those receiving chemotherapy, and very low versus controls without cancer. Cancer patients treated with ICIs seem to be able to receive COVID-19 vaccine safely without increasing the incidence of irAEs.

Compound Kushen injection combined with transarterial chemoembolization for hepatocellular carcinoma: An evidence map and overview of systematic reviews.

ETHNOPHARMACOLOGICAL RELEVANCE: For the treatment of hepatocellular carcinoma (HCC), compound Kushen injection (CKi) is commonly used in combination with transarterial chemoembolization (TACE). AIMS OF THE STUDY: Our objective was to evaluate the reporting quality, methodological quality, risk of bias, and certainty of evidence for CKi combined with TACE for the treatment of patients with HCC by conducting systematic reviews (SRs). The purpose of this study was to improve the clinical application of CKis, strengthen clinical decision-making regarding CKis, and inform future research. MATERIALS AND METHODS: We used eight databases to systematically search SRs of CKi combined with TACE for HCC through February 21, 2023. The quality of reporting of SRs was evaluated using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, methodological quality using A MeaSurement Tool to Assess systematic Reviews 2, risk of bias using the Risk of Bias in Systematic Review, and certainty of evidence using the Grading of Recommendations Assessment. Finally, the assessment results were visualized by the evidence mapping method. This overview has been registered on PROSPERO with the registration title "Compound Kushen injection for hepatocellular carcinoma: An overview of systematic reviews" and registration number CRD42022369120. RESULTS: A total of 12 SRs meeting the inclusion criteria were included. In terms of reporting quality, 42% of SRs reported relatively complete reports and 58% had certain deficiencies. The methodological quality of all SRs was " critically low". The risk of bias was evaluated as low in 33% of SRs and high in 67% of SRs. The results of the evidence synthesis showed that, in the "moderate" level of evidence, CKi combined with TACE resulted in a 12.7%-21.5% benefit for one-year survival rate, 11.7%-17.2% benefit for objective response rate (ORR), 20.5%-27.1% benefit for quality of life, 22.2% benefit for nausea and vomiting, and 24.7%-27.4% benefit for leukopenia in HCC patients. CONCLUSION: In conclusion, CKi combined with TACE improved survival, ORR and quality of life in patients with HCC, and reduced adverse events. The results should be interpreted with caution due to the low methodological quality of the included SRs. The clinical efficacy of CKis must be confirmed in a large number of randomized controlled trials.

Precise Differentiation of Wobble-Type Allele via Ratiometric Design of a Ligase Chain Reaction-Based Electrochemical Biosensor for CYP2C19*2 Genotyping of Clinical Samples.

Due to the comparable stability between the perfect-base pair and the wobble-base pair, a precise differentiation of the wobble-type allele has remained a challenge, often leading to false results. Herein, we proposed a ligase chain reaction (LCR)-based ratiometric electrochemical DNA sensor, namely, R-eLCR, for a precise typing of the wobble-type allele, in which the traditionally recognized "negative" signal of wobble-base pair-mediated amplification was fully utilized as a "positive" one and a ratiometric readout mode was employed to ameliorated the underlying potential external influence and improved its detection accuracy in the typing of the wobble-type allele. The results showed that the ratio between current of methylene blue (IMB) and current of ferrocene (IFc) was partitioned in three regions and three types of wobble-type allele were thus precisely differentiated (AA homozygote: IMB/IFc > 2; GG homozygote: IMB/IFc < 1; GA heterozygote: 1 < IMB/IFc < 2); the proposed R-eLCR successfully discriminated the three types of CYP2C19*2 allele in nine cases of human whole blood samples, which was consistent with those of the sequencing method. These results evidence that the proposed R-eLCR can serve as an accurate and robust alternative for the identification of wobble-type allele, which lays a solid foundation and holds great potential for precision medicine.

Comprehensive analysis of resistance mechanisms to EGFR-TKIs and establishment and validation of prognostic model.

PURPOSE: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for patients with lung adenocarcinoma (LUAD) harboring activating EGFR mutations. However, the emergence of drug resistance to EGFR-TKIs remains a critical obstacle for successful treatment and is associated with poor patient outcomes. The overarching objective of this study is to apply bioinformatics tools to gain insights into the mechanisms underlying resistance to EGFR-TKIs and develop a robust predictive model. METHODS: The genes associated with gefitinib resistance in the LUAD cell Gene Expression Omnibus (GEO) database were identified using gene chip expression data. Functional enrichment analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed to comprehensively explore the mechanism of gefitinib resistance. Furthermore, a GRRG_score was constructed by integrating genes related to LUAD prognosis from The Cancer Genome Atlas (TCGA) database with the screened Gefitinib Resistant Related differentially expressed genes (GRRDEGs) using the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses. Furthermore, we conducted an in-depth analysis of the tumor microenvironment (TME) features and their association with immune infiltration between different GRRG_score groups. A prognostic model for LUAD was developed based on the GRRG_score and validated. The HPA database was used to validate protein expression. The CTR-DB database was utilized to validate the results of drug therapy prediction based on the relevant genes. RESULTS: A total of 110 differentially expression genes were identified. Pathway enrichment analysis of DEGs showed that the differentially expressed genes were mainly enriched in Mucin type O-glycan biosynthesis, Cytokine-cytokine receptor interaction, Sphingolipid metabolism. Gene set enrichment analysis showed that biological processes strongly correlated with gefitinib resistance were cell proliferation and immune-related pathways, EPITHELIAL_MESENCHYMAL_TRANSITION, APICAL_SURFACE, and APICAL_JUNCTION were highly expressed in the drug-resistant group; KRAS_SIGNALING_DN, HYPOXIA, and HEDGEHOG_SIGNALING were highly expressed in the drug-resistant group. The GRRG_score was constructed based on the expression levels of 13 genes, including HSPA2, ATP8B3, SPOCK1, EIF6, NUP62CL, BCAR3, PCSK9, NT5E, FLNC, KRT8, FSCN1, ANGPTL4, and ID1. We further screened and validated two key genes, namely, NUP62CL and KRT8, which exhibited predictive value for both prognosis and drug resistance. CONCLUSIONS: Our study identified several novel GRRDEGs and provided insight into the underlying mechanisms of gefitinib resistance in LUAD. Our results have implications for developing more effective treatment strategies and prognostic models for LUAD patients.

Chinese patent medicine Kanglaite injection for non-small-cell lung cancer: An overview of systematic reviews.

ETHNOPHARMACOLOGICAL RELEVANCE: Kanglaite injection (KLTi), a Chinese herbal medicine, is used as an adjuvant treatment for non-small-cell lung cancer (NSCLC). AIMS OF THE STUDY: To provide an evidence-based endorsement for the clinical application and selection of KLTi by evaluating the reporting quality, methodological quality, risk of bias, and evidence quality of systemic reviews (SRs). MATERIALS AND METHODS: SRs of KLTi adjuvant therapy of NSCLC were searched by using 12 databases, consulting experts, and retrieving relevant conference papers until 2022.03.24. The treatment group received KLTi in combination with other therapies, regardless of dosage, duration, or the therapy combined. Network meta-analyses and SRs using repeated data were excluded. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines 2009, A MeaSurement Tool to Assess systematic Reviews, Risk of Bias in Systematic Review, and the Grading of Recommendations Assessment, Development and Evaluation were used to assess the quality of reports, methodological quality, risk of bias, and level of evidence; R was used for visual analysis of the relevant contents. RESULTS: Twenty SRs (13 Chinese and 7 English articles), all authored by Chinese authors as the first author, were included. The reporting information of most included studies was relatively complete (21-27 points), accounting for three-fourths of the total literature. The quality of the methods used in all studies was critically low. The risk of bias was mostly high. Results of the evidence summary showed that among the "moderate" evidence, KLTi combined with chemotherapy had benefits of 9.7-16.4% for objective response rate (ORR) (11 SRs), 8.1-14% for disease control rate (four SRs), and 20.1-28.6% for quality of life (12 SRs) compared with those of chemotherapy alone. The incidence of gastrointestinal symptoms (five SRs) was reduced by 11.5%-23.2%, while that of leukopenia (four SRs) improved by 19.5-29.2%. Combined radiotherapy and targeted therapy had benefits of 25.9% and 16.8%, respectively, in ORR and 31.3% and 22.8%, respectively, in quality of life (the quality of evidence was "low"). The results depicted that treatment with two courses of KLTi produce the best results. CONCLUSION: Our results suggest that KLTi, whether combined with chemotherapy, radiotherapy, or targeted therapy, has an effect on ORR and quality of life and induces adverse reactions, such as leukopenia, nausea, and vomiting. It may improve patient survival; however, the impact of its low-grade quality on the immune function remains undetermined. Owing to the low reporting quality and methodological quality and high risk of bias of the SRs and the included studies, clinical application of KLTi remains unelucidated; higher-quality SRs and randomized controlled trials are necessary in the future.

Electrochemical immunosensor based on AuNPs/ERGO@CNT nanocomposites by one-step electrochemical co-reduction for sensitive detection of P-glycoprotein in serum.

P-glycoprotein (P-gp), a transmembrane glycoprotein widely expressed on the surface of various cells, is highly associated with multidrug resistance (MDR) that heralds the malignant progress of disease after drug treatment. Notably, there have been reported that serum P-gp is a potential marker for assessing the progression of disease resistance. Currently, there are few methods for point-of-care serum P-gp detection. In this study, we proposed a gold nanoparticles/electrochemically reduced graphene oxide@carbon nanotube (AuNPs/ERGO@CNT) modified immunosensor based on a one-step electrochemical co-reduction method. The limit of detection (LOD) of our constructed electrochemical immunosensor for P-gp detection reached 0.13 ng/mL, and the detection results in serum were consistent with ELISA. The developed immunosensor is expected to provide a scientific basis for the clinical application of serum P-gp monitoring and integrated medicine.

Chinese herbal medicine combined with oxaliplatin-based chemotherapy for advanced gastric cancer: A systematic review and meta-analysis of contributions of specific medicinal materials to tumor response.

Introduction: The incidence and mortality of gastric cancer ranks among the highest, and the 5-year survival rate of advanced gastric cancer (AGC) is less than 10%. Currently, chemotherapy is the main treatment for AGC, and oxaliplatin is an important part of the commonly used chemotherapy regimen for AGC. A large number of RCTs have shown that Chinese herbal medicine (CHM) combined with oxaliplatin-based chemotherapy can improve objective response rate (ORR) and disease control rate (DCR), reduce the toxic and side effects of chemotherapy. There is currently a lack of systematic evaluation of the evidence to account for the efficacy and safety of CHM combined with oxaliplatin-based chemotherapy in AGC. Therefore, we carried out this study and conducted the sensitivity analysis on the herbal composition to explore the potential anti-tumor efficacy. Methods: Databases of PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Wanfang database, and the Chinese Scientific Journals Database were searched from their inception to April 2022. RCTs evaluating the efficacy of CHM combined with oxaliplatin-based chemotherapy on AGC were included. Stata 16 was used for data synthesis, RoB 2 for quality evaluation of included RCTs, and GRADE for quality of synthesized evidence. Additional sensitivity analysis was performed to explore the potential anti-tumor effects of single herbs and combination of herbs. Results: Forty trials involving 3,029 participants were included. Most included RCTs were assessed as "Some concerns" of risk of bias. Meta-analyses showed that compare to oxaliplatin-based chemotherapy alone, that CHM combined with oxaliplatin-based chemotherapy could increase the objective response rate (ORR) by 35% [risk ratio (RR) = 1.35, 95% confidence intervals (CI) (1.25, 1.45)], and disease control rate (DCR) by 12% [RR = 1.12, 95% CI (1.08, 1.16)]. Subgroup analysis showed that compare to SOX, FOLFOX, and XELOX regimens alone, CHM plus SOX, CHM plus FOLFOX, and CHM plus XELOX could significantly increase the ORR and DCR. Sensitivity analysis identified seven herbs of Astragalus, Liquorice, Poria, Largehead Atractylodes, Chinese Angelica, Codonopsis, and Tangerine Peel with potentials to improve tumor response of oxaliplatin-based chemotherapy in AGC. Conclusion: Synthesized evidence showed moderate certainty that CHM plus oxaliplatin-based chemotherapy may promote improvement in tumor response in AGC. CHM treatment is safe for AGC. Due to the poor quality of included RCTs and small samplesizes, the quality of synthesized evidence was not high. Specific combinations of herbs appeared to produce higher contributions to ORR than the herb individually. Each of this seven above mentioned herbs has been shown in experimental studies to potentially contribute to the improvement of tumor response. To support this conclusion, these seven herbs are worthy of further clinical research. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262595], identifier [CRD42022262595].

Efficacy and Safety of EGFR Tyrosine Kinase Inhibitors Combined with Cranial Radiotherapy for Brain Metastases from Non-Small-Cell Lung Cancer: A Protocol for a Systematic Review and Meta-Analysis.

Introduction. Brain metastases (BMs) are common in non-small-cell lung cancer (NSCLC), which leads to a poor prognosis. As the two most effective strategies available, the use of combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and radiotherapy (RT) is still controversial. This protocol proposes a methodology for carrying out a systematic review and meta-analysis that is aimed at (1) focusing on the efficacy and safety role of EGFR-TKIs combined with RT for BMs from NSCLC and (2) displaying the difference in efficacy of EGFR-TKIs owing to the sites and number of BMs, different types of RT, EGFR mutation status, and the subtypes of EGFR mutations by subgroup analysis. Methods and Analysis. Electronic databases including PubMed, Embase, CENTRAL, Web of Science, CBM, CNKI, Wanfang database, and VIP database will be searched from their inception until May 2022. Only randomized controlled trials evaluating the clinical efficacy and safety of EGFR-TKIs combined with RT on BMs of NSCLC will be included. Two reviewers will select the articles, assess the risk of bias, and extract data independently and in duplicate. The RoB 2 tool will be used to assess the quality of included studies. The meta-analysis of data synthesis will be performed with Stata 16. Publication bias will be assessed with the funnel plot method and the Egger test. Quality of the evidence will be evaluated by the GRADE system. Discussion. The approval of an ethical committee is not required. All the included trials will comply with the current ethical standards and the Declaration of Helsinki. Given the ongoing controversies regarding the optimal sequencing of the available and expanding treatment options for EGFR-TKIs in NSCLC with BMs, a synthesis of available, high-quality clinical research evidence is essential to advance our understanding in the treatment of this complex and common disease. This systematic review will evaluate available evidence, will try to provide optimized advice in the applications of EGFR-TKIs, and will be published in a high-quality journal. This study is registered with PROSPERO registration number CRD42021291509.

Multimodal Ochratoxin A-Aptasensor Using 3'-FAM-Enhanced Exonuclease I Tool and Magnetic Microbead Carrier.

Thanks to its preparatory ease, close affinity, and low cost, the aptasensor can serve as a promising substitute for antibody-dependent biosensors. However, the available aptasensors are mostly subject to a single-mode readout and the interference of unbound aptamers in solution and non-target-induced transition events. Herein, we proposed a multimodal aptasensor for multimode detection of ochratoxin A (OTA) with cross-validation using the 3'-6-carboxyfluorescein (FAM)-enhanced exonuclease I (Exo I) tool and magnetic microbead carrier. Specifically, the 3'-FAM-labeled aptamer/biotinylated-cDNA hybrids were immobilized onto streptavidin-magnetic microbeads via streptavidin-biotin interaction. With the presence of OTA, an antiparallel G-quadruplex conformation was formed, protecting the 3'-FAM labels from Exo I digestion, and then anti-FAM-horseradish peroxidase (HRP) was bound via specific antigen-antibody affinity; for the aptamers without the protection of OTA, the distal ssDNA was hydrolyzed from 3' → 5', releasing 3'-FAM labels to the solution. Therefore, the OTA was detected by analyzing the "signal-off" fluorescence of the supernatant and two "signal-on" signals in electrochemistry and colorimetry through the detection of the coating magnetic microbeads in HRP's substrate. The results showed that the 3'-FAM labels increased the activity of Exo I, producing a low background due to a more thorough digestion of unbound aptamers. The proposed multimodal aptasensor successfully detected the OTA in actual samples. This work first provides a novel strategy for the development of aptasensors with Exo I and 3'-FAM labels, broadening the application of aptamer in the multimode detection of small molecules.

Efficacy and Safety of Brucea javanica Oil Emulsion Injection in the Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis.

Background: Gastric cancer (GC) is one of the most common digestive tract cancers and ranks fifth in the incidence of malignant tumors worldwide. Brucea javanica oil emulsion injection (BJOEI), a Chinese patent medicine extracted from Brucea javanica (Yadanzi in Chinese Pinyin), is widely used as an adjuvant treatment for GC in China. This systematic review and meta-analysis aimed to evaluate the available data on the efficacy and safety of BJOEI in the treatment of GC and assess the quality of the synthesized evidence. Methods: A comprehensive search was performed on PubMed, EMBASE, CENTRAL, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and Chinese Scientific Journals Database (VIP database), and other potential resources, such as the Chinese Clinical Trial Registry (ChiCTR) and ClinicalTrials.gov from their inception to July 31, 2021. Randomized controlled trials (RCTs) comparing the therapeutic effects of BJOEI combined with conventional therapy to those of conventional therapy alone were included. We used RevMan 5.3 for data analysis and quality evaluation of the included studies and assessed the evidence quality based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results: Eighteen RCTs involving 1,210 patients were included, and the meta-analysis results demonstrated that compared with the control group (conventional therapy), the experimental group (BJOEI combined with conventional therapy) showed a significantly improved overall response rate (ORR) (risk ratio [RR] = 1.52, 95% CI: 1.36-1.69, P < 0.00001), clinical benefit rate (CBR) (RR = 1.17, 95% CI: 1.11-1.23, P < 0.00001), performance status (RR = 1.72, 95% CI: 1.46-2.01, P < 0.00001), and reduced incidence of the following adverse drug reactions (ADRs): neutropenia, leukopenia, nausea and vomiting, diarrhea, liver damage, hand-foot syndrome, and peripheral sensory nerve toxicity. Subgroup analysis showed that the BJOEI intervention could significantly improve the ORR and CBR in patients with GC when combined with FOLFOX4, XELOX, and other chemotherapeutics. Conclusion: The evidence presented in this study supports the fact that BJOEI combined with conventional chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, CBR, performance status, and ADR reduction in patients with GC. To further support this conclusion, more rigorously designed, large-scale, and multicenter RCTs are needed in the future.

Traditional Chinese Medicine Therapy for Esophageal Cancer: A Literature Review.

Esophageal cancer (EC) is the sixth leading cause of cancer-related deaths worldwide. Western medicine has played a leading role in its treatment, but its prognosis remains unsatisfactory. Therefore, the development of effective therapies is important. Traditional Chinese medicine (TCM) has been practiced for thousands of years, and involves taking measures before diseases occur, deteriorate, and recur. Interestingly, there is growing evidence that TCM can improve the therapeutic effects in reversing precancerous lesions, inhibiting the recurrence and metastasis of EC. In this article, we review traditional Chinese herbs and formulas that have preventive and therapeutic effects on EC, summarize the application and research status of TCM in patients with EC, and discuss its shortcomings and prospects in the context of translational, evidence-based, and precision medicine.

Efficacy and Safety of Brucea javanica Oil Emulsion Injection for Treating Gastric Cancer: A Protocol for a Systematic Review and Meta Analysis.

Introduction. Brucea javanica oil emulsion injection (BJOEI) is an antitumor drug extracted from the traditional Chinese medicinal plant Brucea javanica, which has broad prospects as an adjuvant treatment for gastric cancer (GC); however, its efficacy and safety are still controversial. We plan to conduct a systematic review and meta-analysis to summarise the clinical efficacy and safety of BJOEI in the treatment of GC and provide credible evidence for the clinical application and subsequent studies of BJOEI. Methods and Analysis. This systematic review will include articles identified by electronically searching the following databases: PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journals Database (VIP Database) from inception to 31 July 2021. The primary outcomes of this research will be the clinical total effective rate, performance status, and adverse drug reactions (ADRs). The systematic review will be performed using RevMan 5 software. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluation System (GRADE) to assess the quality of evidence. Ethics and Dissemination. Ethical approval is not required for literature-based studies. The results of this systematic review will be published in a peer-reviewed journal. PROSPERO registration number: CRD42021265646.

A potentially valuable nano graphene oxide/USPIO tumor diagnosis and treatment system.

Due to increased requirements for precision cancer treatment, cancer chemotherapy and combination therapies have gradually developed in the direction of diagnosis and treatment integration. In this study, a non-toxic nano carrier that demonstrates integrated MRI signal enhancing performance, as well as better chemotherapy and photothermal conversion performance, was prepared and characterized. Furthermore, the carrier was used to construct an integrated system of tumor diagnosis and treatment. Our in vitro studies showed that this system has a considerable inhibition effect on tumor cells during the treatment of chemotherapy when combined with PTT, and in vivo studies showed that the system could improve the MRI signal of the tumor site with application of a safe dosage. Thus, this system based on NGO/USPIO has the potential to be a multi-functional nano drug delivery system integrating diagnosis and treatment benefits and applications that are worthy of further research.

Functionalized Graphene Oxide as Drug Delivery Systems for Platinum Anticancer Drugs.

Graphene Oxide, prepared by the modified Hummer's method, was modified with a series of high polymers (polyethyleneimine, polyethylene glycol, chitosan) and Folic Acid for the delivery of platinum anticancer drugs including Cisplatin, Carboplatin, Oxaliplatin and Eptaplatin. Nanocarriers were successfully prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscope. Measurement of drug loading efficiency showed that these nanocarriers had the ability for effective delivery of the platinum anticancer drugs. The Maximum loading ratios of Cisplatin, Carboplatin, Oxaliplatin and Eptaplatin were 25.72, 161.08, 345.21 and 67.80 µg/mg. Drug release experiments in the acid environment showed that the cumulative release rate of platinum anticancer drugs from nanocarriers was higher than that in the neutral environment. The cumulative release of all three nanocarriers in the acid environment reached above 60%. In vitro cytotoxicity assay showed that those nanocarriers had a low toxicity. The cell viability rates were above 80% for all three nanocarriers. Investigation of the anticancer activity in vitro showed that those drug delivery systems had the ability to inhibit the growth of the SKOV3 cell line. These results showed that those nanocarriers were suitable for the delivery of platinum anticancer drugs. Providing preliminary advice on the potential application of the combination of platinum anticancer drugs and the functionalized Graphene Oxide nanocarriers.