High-dose dual therapy versus bismuth-containing quadruple therapy for the eradication of Helicobacter pylori: A systematic review and meta-analysis.

OBJECTIVE: To update evidence-based data comparing the efficacy and safety of high-dose dual therapy (HDDT) and bismuth-containing quadruple therapy (BQT) in eradicating Helicobacter pylori infection through meta-analysis. METHODS: Multiple databases were systematically searched for randomized controlled trials (RCTs) published up to May 18, 2023. Dichotomous data were evaluated using risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis, sensitivity analysis, risk of bias assessment, and quality of evidence evaluation were performed. RESULTS: Twenty RCTs containing 7891 subjects were included in the analysis. There was no statistically significant difference in H. pylori eradication rate between HDDT and BQT in the intention-to-treat (ITT) analysis (86.31% vs 84.88%; RR 1.02, 95% CI 1.00-1.04, P = 0.12). In the per-protocol (PP) analysis, the eradication rates for HDDT and BQT were 90.27% and 89.94%, respectively (RR 1.01, 95% CI 0.99-1.03, P = 0.44). Adverse events were significantly lower with HDDT than with BQT (RR 0.44, 95% CI 0.38-0.51, P < 0.00001). Patient adherence was significantly different between the two groups (RR 1.01, 95% CI 1.00-1.03, P = 0.02). Subgroup analysis based on antibiotic combinations within the BQT group showed a significantly higher eradication rate for HDDT than for BQT only when BQT used amoxicillin combined with clarithromycin (P = 0.0009). CONCLUSIONS: HDDT showed comparable efficacy with BQT for H. pylori eradication, with fewer adverse effects and higher compliance. Due to regional differences, antibiotic resistance rates, and combined BQT antibiotics, more studies are needed for further validation and optimization of HDDT.

Knowledge, attitude, and practice of monitoring early gastric cancer after endoscopic submucosal dissection.

BACKGROUND: Early gastric cancer (EGC) is typically treated with endoscopic submucosal dissection (ESD). However, recurrence may occur after ESD, requiring surveillance. AIM: To examine the knowledge, attitude, and practice (KAP) of EGC survivors following ESD regarding gastric cancer recurrence. METHODS: This cross-sectional study was conducted between June 1, 2022 and October 1, 2022 in Zhejiang, China. A total of 400 EGC survivors who underwent ESD at the Affiliated Jinhua Hospital, Zhejiang University School of Medicine participated in this study. A self-administered questionnaire was developed to assess KAP monitoring gastric cancer after ESD. RESULTS: The average scores for KAP were 3.34, 23.76, and 5.75 out of 5, 30, and 11, respectively. Pearson correlation analysis revealed positive and significant correlations between knowledge and attitude, knowledge and practice, and attitude and practice (r = 0.405, 0.511, and 0.458, respectively; all P < 0.001). Multivariate logistic regression analysis showed that knowledge, attitude, 13-24 mo since the last ESD (vs ≤ 12 mo since the last ESD), and ≥ 25 mo since the last ESD (vs ≤ 12 mo since the last ESD) were independent predictors of proactive practice (odds ratio = 1.916, 1.253, 3.296, and 5.768, respectively, all P < 0.0001). CONCLUSION: EGC survivors showed inadequate knowledge, positive attitude, and poor practices in monitoring recurrences after ESD. Adequate knowledge, positive attitude, and a longer time since the last ESD were associated with practice.

[Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species].

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 µL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial.

BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Chuanxiong improves angiogenesis via the PI3K/AKT/Ras/MAPK pathway based on network pharmacology and DESI-MSI metabolomics.

Introduction: Chuanxiong, a traditional Chinese medicine, has been proved to treat a variety of cardiovascular and cerebrovascular diseases by promoting angiogenesis. However, the mechanisms of Chuanxiong's pro-angiogenesis is currently unknown. This study aimed to uncover the effect and mechanisms of Chuanxiong promoting angiogenesis in vivo and in vitro. Methods: First, potential targets were predicted by network pharmacology analysis, and PPI network was established and the pathways were enriched. Then, the chorioallantoic membrane test on quails was applied to assess the proangiogenic effects in vivo. As well, to evaluate the effects in vitro, real-time PCR, western blot analysis, the scratch test, and the tube formation experiment were used. Subsequently, the major metabolic pathways were analyzed using non-targeted metabolomics. Results: As a result of network pharmacological analysis, 51 collective targets of Chuanxiong and angiogenesis were identified, which are mainly associated with PI3K/AKT/Ras/MAPK pathway. And the biological verification results showed that Chuanxiong could increase the vessel numbers and vessel area in qCAM models. Meanwhile, Chuanxiong contributed to HUVEC proliferation, tube formation, migration, by encouraging scratch healing rates and boosting tube branch points. In addition, the levels of VEGFR2, MAPK and PI3K were elevated compared to the control group. The western blot analysis also confirmed Chuanxiong could promote an increase in AKT, FOXO1 and Ras. Furtheremore, metabolomic results showed that the proangiogenic effect of Chuanxiong is associated with glycine, serine and threonine metabolism. Discussion: In conclusion, this study clarified that Chuanxiong could promote angiogenesis in vivo and in vitro via regulating PI3K/AKT/Ras/MAPK pathway.

A strategy combining chemical analysis and network pharmacology to investigate the mechanism of Xiao'er Qingre Zhike Oral solution in cough.

Xiao'er Qingre Zhike Oral Solution (XQZS) is a commonly used TCM formula to treat cough in children in China. Its complicated composition renders its chemical analysis and mechanism elucidation difficult. To evaluate the bioactive components and mechanism of XQZS against cough, we used a combination strategy of chemical analysis and network pharmacology. A UHPLC/Q-Orbitrap-MS method was established for the identification and qualitative analysis of components of XQZS, and a total of 33 components were unambiguously identified. Aiming at identifying the components, network pharmacology revealed 107 potential targets related to cough. Using protein-protein interactions analysis, nine core targets were selected. Several cough-related pathways were enriched using the Kyoto Encyclopedia of Genes and Genomes, including neuroactive ligand-receptor interaction, serotonergic synapse and dopaminergic synapse. The herb-compound-target-pathway network indicated that PTGS2 (COX-2) was the core target of XQZS against cough. To demonstrate the inhibition effects of the major components against the key target, a COX-2 inhibitor screening assay was used. Compounds P2, P4, P23 and P49 exhibited promising inhibition effects on COX-2 at 20 µm, with inhibitory rates of 55.80-69.87%. In conclusion, this study demonstrates that XQZS may alleviate cough via the inhibition of PTGS2 (COX-2) and the regulation of the serotonergic synapse pathway. The chemical analysis and network pharmacology integrated evaluation provided an efficient strategy for discovering the key pharmacological mechanism of XQZS.

Design and synthesis of novel anti-multidrug-resistant staphylococcus aureus derivatives of glycyrrhetinic acid by blocking arginine biosynthesis, metabolic and H2S biogenesis.

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125-25 µM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC > 200 µM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 µM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H2S biogenesis. Importantly, compound 11 was confirmed to have good biocompatibility through the in vitro hemolysis tests, cytotoxicity assays and the in vivo quail chicken chorioallantoic membrane (qCAM) experiments. Current study provided new potential antibacterial candidates from glycyrrhetinic acid derivatives for clinical treatment of MRSA infections.

Endoscopic mucosal resection-precutting vs conventional endoscopic mucosal resection for sessile colorectal polyps sized 10-20 mm.

BACKGROUND: The optimal method to remove sessile colorectal lesions sized 10-20 mm remains uncertain. Piecemeal and incomplete resection are major limitations in current practice, such as endoscopic mucosal resection (EMR) and cold or hot snare polypectomy. Recently, EMR with circumferential precutting (EMR-P) has emerged as an effective technique, but the quality of current evidence in comparative studies of conventional EMR (CEMR) and EMR-P is limited. AIM: To investigate whether EMR-P is superior to CEMR in removing sessile colorectal polyps. METHODS: This multicenter randomized controlled trial involved seven medical institutions in China. Patients with colorectal polyps sized 10-20 mm were enrolled and randomly assigned to undergo EMR-P or CEMR. EMR-P was performed following submucosal injection, and a circumferential mucosa incision (precutting) was conducted using a snare tip. Primary outcomes included a comparison of the rates of en bloc and R0 resection, defined as one-piece resection and one-piece resection with histologically assessed clear margins, respectively. RESULTS: A total of 110 patients in the EMR-P group and 110 patients in the CEMR group were finally evaluated. In the per-protocol analysis, the proportion of en bloc resections was 94.3% [95% confidence interval (CI): 88.2%-97.4%] in the EMR-P group and 86% (95%CI: 78.2%-91.3%) in the CEMR group (P = 0.041), while subgroup analysis showed that for lesions > 15 mm, EMR-P also resulted in a higher en bloc resection rate (92.0% vs 58.8% P = 0.029). The proportion of R0 resections was 81.1% (95%CI: 72.6%-87.4%) in the EMR-P group and 76.6% (95%CI: 68.8%-84.4%) in the CEMR group (P = 0.521). The EMR-P group showed a longer median procedure time (6.4 vs 3.0 min; P < 0.001). No significant difference was found in the proportion of patients with adverse events (EMR-P: 9.1%; CEMR: 6.4%; P = 0.449). CONCLUSION: In this study, EMR-P served as an alternative to CEMR for removing nonpedunculated colorectal polyps sized 10-20 mm, particularly polyps > 15 mm in diameter, with higher R0 and en bloc resection rates and without increasing adverse events. However, EMR-P required a relatively longer procedure time than CEMR. Considering its potential benefits for en bloc and R0 resection, EMR-P may be a promising technique in colorectal polyp resection.

Clinicopathological characteristics and prognostic factors of elderly small intestine adenocarcinoma using propensity score matching analysis: a study based on SEER database.

BACKGROUND: Small intestine adenocarcinoma (SIA) is a scant disease that has no adequate clinical trials, so its prognostic factors are still unclear, especially in elderly patients. In this article, we aimed to explore the clinicopathology presentation, treatments, outcomes, and predictors of small intestine adenocarcinoma patients aged 65 years or older. METHODS: We retrieved clinicopathology data of small intestine adenocarcinoma patients diagnosed between 2004 and 2015 from the Surveillance Epidemiology and End Results (SEER) database. We clarified patients into two groups: the surgery and the non-surgery group and conducted propensity score matching (PSM) to compare survival outcoming. We identified the prognostic indicators for cancer-specific survival (CSS) and overall survival (OS) by the Cox proportional hazards model. RESULTS: In total, 1018 eligible cases were enrolled, with a median survival of 16 months; the 3-year OS and CSS rates were 36% and 41.7%, and the 5-year OS and CSS rates were 26.5% and 33.3%. Multivariate analyses revealed that age, grade, tumor stage, surgery, and chemotherapy were independent prognostic factors for OS, while grade, tumor stage, surgery, radiation, and chemotherapy were independent factors for CSS. After PSM, only surgery and tumor stage (AJCC 6th) were independent prognostic factors for OS and CSS. CONCLUSION: Surgery could bring benefit to survival for elderly SIA patients, and the early stage of the disease was another significant prognostic factor.

Synthesis and biological activity evaluation of podophyllotoxin-linked bile acid derivatives as potential anti-liver cancer agents.

Podophyllotoxin's undifferentiated cytotoxicity and poor selectivity limit its clinical application. To improve above disadvantages, conjugation of bile acids with podophyllotoxin could improve cell line selectivity of liver cancer to achieve clinical translation further. Enlightened by the bile acids' moiety magic characters, thirty podophyllotoxin-linked bile acid derivatives had been designed and synthesized. The cytotoxicity of these compounds in vitro was evaluated on HepG2, HCT-116, A549 and MDCK cell lines. After conjunction with bile acids, most of the derivatives (IC50 = 0.066-0.831 µM) were more potent against above three types of tumor cells than Etoposide (VP-16, IC50 = 4.319-41.080 µM) and exhibited similar antitumor activity compared with doxorubicin (DOX, IC50 = 0.230-0.745 µM). Moreover, structure-activity relationship displayed the length of the linker chain between podophyllotoxin and bile acids affected the cytotoxicity. Especially, compound 23 exhibited strong activity against HepG2 cell lines (IC50 = 0.188 ± 0.01 µM) than MDCK cell lines (IC50 = 4.780 ± 0.50 µM) and its SI (IC50MDCK/IC50HepG2) value of compound 23 was 25.4. Further antitumor mechanism studies showed that compound 23 acted as Topo Ⅱ inhibition and induced cell apoptosis with S cell cycle arrest. In particular, compound 23 showed valid antitumor efficacy at 10 mg/kg by intraperitoneal administration with a tumor inhibition rate of 60.9% in the Hepa1-6 xenograft mice model. The current research displayed that introduction of bile acids contributed to improve selectivity and activity to cell, and compound 23 could be a promising anti-tumor candidate.

Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Talaromyces marneffei Infections.

Background: Although anti-IFN-γ autoantibodies predispose patients to Talaromyces marneffei infection, whether this is mediated by T cell attenuation remains elusive. Methods: Total peripheral blood mononuclear cells (PBMCs) from healthy donors or patients with T. marneffei infection were stimulated with M158-66, and immunodominant influenza H1N1 peptide, or heat-inactivated T. marneffei in the presence of serum from anti-IFN-γ autoantibody-positive patients or healthy controls. The percentages of IFN-γ+TNF+CD8+ T cells and IFN-γ+CD4+ T cells were determined by flow cytometry and cytokines released in the supernatant were detected by Cytometric Bead Array. Furthermore, PBMCs from patients with T. marneffei infection and healthy individuals were stimulated with IFN-γ and anti-CD3/CD28 beads, and the levels of STAT1 and STAT3 phosphorylation were detected by Western blot. Results: The M1-reactive CD8+ T cells that expressed IFN-γ+ TNF-α+ of healthy controls were clearly reduced in serum with high-titer anti-IFN-γ autoantibodies. In addition, the CD4+ T cell response, designated by the expression of IFN-γ, against T. marneffei in PBMCs of patients were significantly decreased when cultured in high-titer anti-IFN-γ autoantibody serum culture, compared to the healthy compartments. Moreover, the release of the cytokines IFN-γ, TNF-α and IL-2 was significantly decreased, while IL-10 was significantly increased. There was no significant difference in the phosphorylation levels of STAT1 and STAT3 protein between patients and healthy controls after IFN-γ or anti-CD3/CD28 beads stimulation. Conclusion: Anti-IFN-γ autoantibodies presence in the serum inhibited CD4+ Th1 and CD8+ T cell immune responses. There was no congenital dysfunction of STAT1 and STAT3 in anti-IFN-γ autoantibody-positive patients with T. marneffei infection. These results suggest that the production of anti-IFN-γ autoAbs impair T-lymphocyte responses.

A simple and rapid mix-and-read assay for sensitive detection of O6-methylguanine DNA methyltransferase.

We have developed a simple and rapid mix-and-read assay for the sensitive detection of O6-methylguanine DNA methyltransferase (MGMT) activity based on exonuclease III-assisted signal amplification under completely isothermal conditions (37 °C). This method is very simple and rapid (60 min) with ultrahigh sensitivity and good specificity, and it can detect MGMT activity at the single-cell level. Moreover, this method can be applied for the screening of MGMT inhibitors and the discrimination of MGMT in different cancer cells.

Organoid Models for Precision Cancer Immunotherapy.

Cancer immunotherapy is exploited for the treatment of disease by modulating the immune system. Since the conventional in vivo animal and 2D in vitro models insufficiently recapitulate the complex tumor immune microenvironment (TIME) of the original tumor. In addition, due to the involvement of the immune system in cancer immunotherapy, more physiomimetic cancer models, such as patient-derived organoids (PDOs), are required to evaluate the efficacy of immunotherapy agents. On the other hand, the dynamic interactions between the neoplastic cells and non-neoplastic host components in the TIME can promote carcinogenesis, tumor metastasis, cancer progression, and drug resistance of cancer cells. Indeed, tumor organoid models can properly recapitulate the TIME by preserving endogenous stromal components including various immune cells, or by adding exogenous immune cells, cancer-associated fibroblasts (CAFs), vasculature, and other components. Therefore, organoid culture platforms could model immunotherapy responses and facilitate the immunotherapy preclinical testing. Here, we discuss the various organoid culture approaches for the modeling of TIME and the applications of complex tumor organoids in testing cancer immunotherapeutics and personalized cancer immunotherapy.

Quality Improvement of Sample Collection Increases the Diagnostic Accuracy of Quantitative Fecal Immunochemical Test in Colorectal Cancer Screening: A Pilot Study.

Objective: The diagnostic efficiency of the quantitative fecal immunochemical test (qFIT) has large variations in colorectal cancer (CRC) screening. We aimed to explore whether the practical sample collection operant training could improve the diagnostic accuracy of the qFIT in CRC screening. Methods: Moderate-/high-risk individuals aged 50-75 years old were invited to participate in a prospective observational study between July 2020 and March 2021. Participants took a qFIT sample without fecal sample collection operant training in advance and then completed another qFIT sample after the operant training. The primary outcome was the sensitivity and specificity of the qFITs for CRC and advanced colorectal neoplasia (ACRN). The secondary outcome was the difference in the area under the curves (AUCs) and the concentrations of the fecal hemoglobin (Hb) between the qFIT without and after the operant training. Results: Out of 913 patients, 81 (8.9%) patients had ACRN, including 25 (2.7%) patients with CRC. For CRC, the sensitivities of the qFIT without and after the operant training at 10 µg/g were 80.4 and 100.0%, respectively, and the specificities were 90.1 and 88.4%, respectively. For ACRN, the sensitivities were 49.4 and 69.1% and the specificities were 91.7 and 91.3%, respectively. The AUC of the qFIT after the operant training was significantly higher than that without the operant training for CRC (p = 0.027) and ACRN (p = 0.001). After the operant training, the concentration of the fecal Hb was significantly higher than that without the operant training (p = 0.009) for ACRN, but there was no significant difference for CRC (p = 0.367). Conclusion: Practical sample collection operant training improves the diagnostic accuracy of the qFIT, which increases the detection of the low concentrations of fecal Hb. Improving the quality of the sample collection could contribute to the diagnostic efficiency of the qFIT in CRC screening.

The Prediction Potential of the Pretreatment Lung Immune Prognostic Index for the Therapeutic Outcomes of Immune Checkpoint Inhibitors in Patients With Solid Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The lung immune prognostic index (LIPI) is recently developed to predict immune checkpoint inhibitors (ICIs) treatment outcomes for non-small cell lung cancer. However, its predictive value for other types of cancer remained unclear. This meta-analysis aimed to evaluate the association between pretreatment LIPI score and therapeutic outcomes in cancer patients treated with ICIs. METHODS: We searched PubMed, Cochrane Library literature databases and EMBASE for abstracts and full-text articles published from the inception of the database until 16th, Nov 2020. Meta-analyses were performed separately for progression-free survival (PFS) and overall survival (OS) by using the random-effects model. RESULTS: A total of 12 studies involving 4883 patients receiving ICIs treatment were identified for the primary analysis. The pooled results implied that compared with good LIPI score groups, patients with poor or intermediate LIPI score were significantly associated with worse OS (HR=3.33, 95%CI 2.64-4.21, P < 0.001, I2 = 64.2%; HR=1.71, 95%CI 1.43-2.04, P < 0.001, I2 = 43.6%, respectively) and PFS (HR=2.73,95%CI 2.00-3.73, P < 0.001, I2 = 78.2%; HR=1.43, 95%CI 1.28-1.61, P < 0.001, I2 = 16.3%, respectively). Also, for 1873 patients receiving chemotherapy, a poor LIPI score was significantly associated with worse OS (HR=2.30, 95%CI 1.73-3.07, P < 0.001; I2 = 56.2%) and PFS (HR=1.92,95%CI 1.69-2.17; P < 0.001; I2 = 0.0%) compared with good LIPI score groups. CONCLUSIONS: A good LIPI score was significantly correlated with improved OS and PFS in cancer patients receiving ICIs or chemotherapy, regardless of the types of cancer.

Combination of bidirectional strand displacement amplification with single-molecule detection for multiplexed DNA glycosylases assay.

DNA glycosylases can initiate base excision repair pathway to repair endogenous DNA base damages for the maintenance of genome stability. Multiple DNA glycosylases exhibit abnormal in various diseases, and the simultaneous measurement of different DNA glycosylases is critical to clinical diagnosis and drug discovery. Herein, we take advantage of single-molecule detection and bidirectional strand displacement amplification (SDA) to simultaneously detect uracil DNA glycolase (UDG) and human alkyladenine DNA glycosylase (hAAG). We design a partial double-stranded DNA (dsDNA) substrate modified with specific recognition sites of UDG and hAAG. The dsDNA substrate is labeled with BHQ1 and BHQ2 at the 5'-ends and then hybridizes with the Cy3/Cy5-labeled reporter probes to obtain the BHQ1/Cy3 and BHQ2/Cy5 base pairs, resulting in the quenching of Cy3/Cy5 fluorescence by BHQ1/BHQ2 via fluorescence resonance energy transfer (FRET). When UDG and hAAG are present, they can induce the base excision repair reaction and subsequently initiate the bidirectional SDA amplification process, releasing the Cy5/Cy3-labeled reporter probes from the dsDNA substrate and consequently the recovery of Cy5 and Cy3 fluorescence, which can be measured by single-molecule detection, with Cy5 indicating UDG and Cy3 indicating hAAG. This method possesses high sensitivity and good selectivity with the capability of quantifying multiple DNA glycosylases at the single-cell level. Furthermore, it can be used to simultaneously screen DNA glycosylase inhibitors and determine enzyme kinetic parameters, with the potential of sensing various DNA/RNA enzymes by simple changing the recognition sites of DNA substrates.

Diffuse xanthoma in early esophageal cancer: A case report.

BACKGROUND: Gastrointestinal xanthomas are asymptomatic and infrequent non-neoplastic lesions that commonly occur in the stomach with Helicobacter pylori-associated gastritis and rarely in the esophagus. To date, there have been no reports of esophageal xanthoma combined with esophageal cancer. Herein, we present the first case in the literature of a diffuse xanthoma complicated with early esophageal cancer. Moreover, this combination makes the endoscopic diagnosis difficult if it is not in mind. CASE SUMMARY: A 68-year-old man visited our department with a 2-mo history of epigastric discomfort. He underwent surgery for gastric cancer 6 years ago. Esophagogastroduodenoscopy showed a semi-circumferential irregular yellowish-colored and granular lesion in the esophagus (30-35 cm from the incisors). Using magnifying endoscopy with narrow band imaging, aggregated minute and yellowish-colored spots with tortuous microvessels on the surface were observed, and background coloration was clearly seen in the lesion. As endoscopic biopsy suggested a histologically high-grade dysplasia; the lesion was completely resected en bloc by endoscopic submucosal dissection (ESD). The resected specimen was confirmed to be a squamous cell carcinoma in situ with extensive foamy cells in the superficial mucosal layer. Immunohistochemically, the observed foamy cells were strongly positive for CD68, which is characteristic of xanthoma. The clinical course was favorable, and no recurrence was observed 2 years and 7 mo after ESD. CONCLUSION: Diffuse xanthoma concurrent with early esophageal cancer is extremely rare. The characteristic endoscopic features may assist endoscopists in diagnosing similar lesions.

RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival.

Angiogenesis and immunosuppression have been described as closely related processes that can occur in parallel. As an inhibitor of matrix metalloproteinase, whether the level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in hepatocellular carcinoma (HCC) reflects a link between angiogenesis and immunosuppression is still unknown. We analyzed RNA expression, immune infiltration and survival of HCC from The Cancer Genome Atlas databases. Immune scores and stromal scores were calculated based on the ESTIMATE algorithm to quantify the immune and stromal components in HCC. The association between RECK and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high RECK expression was significantly better than that of patients with low RECK expression. High RECK expression was associated with high ESTIMATE Score, recruitment of more tumor-infiltrating lymphocytes, low tumor purity, and high PD-L1 expression. In addition, positive RECK expression was associated with a lower incidence of vascular invasion and recurrence, a lower level of alpha fetoprotein (AFP) and microvessel density and a better tumor differentiation. Multivariate analyses revealed that reduced RECK expression was an independent prognostic factor for recurrence and poor prognosis. In conclusion, high RECK expression reflects an immunogenic and hypovascularity status in HCC. RECK is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive anti-angiogenic therapy or immunotherapy.

Real-time artificial intelligence for endoscopic diagnosis of early esophageal squamous cell cancer (with video).

BACKGROUND AND AIMS: Endoscopic diagnosis of early esophageal squamous cell cancer (ESCC) is complicated and dependent on operators' experience. This study aimed to develop an artificial intelligence (AI) model for automatic diagnosis of early ESCC. METHODS: Non-magnifying and magnifying endoscopic images of normal/noncancerous lesions, early ESCC, and advanced esophageal cancer (AEC) were retrospectively obtained from Qilu Hospital of Shandong University. A total of 10,988 images from 5075 cases were chosen for training and validation. Another 2309 images from 1055 cases were collected for testing. One hundred and four real-time videos were also collected to evaluate the diagnostic performance of the AI model. The diagnostic performance of the AI model was compared with endoscopists by magnifying images and the assistant efficiency of the AI model for novices was evaluated. RESULTS: The AI diagnosis for non-magnifying images showed a per-patient accuracy, sensitivity, and specificity of 99.5%, 100%, 99.5% for white light imaging, and 97.0%, 97.2%, 96.4% for optical enhancement/iodine straining images. Regarding diagnosis for magnifying images, the per-patient accuracy, sensitivity, and specificity were 88.1%, 90.9%, and 85.0%. The diagnostic accuracy of the AI model was similar to experts (84.5%, P = 0.205) and superior to novices (68.5%, P = 0.005). The diagnostic performance of novices was significantly improved by AI assistance. When it comes to the diagnosis for real-time videos, the AI model showed acceptable performance as well. CONCLUSIONS: The AI model could accurately recognize early ESCC among noncancerous mucosa and AEC. It could be a potential assistant for endoscopists, especially for novices.