Hue-change coupled with CRISPR-Cas12a lateral flow assay for the semiquantitative detection of Salmo salar adulteration.

Salmo salar is one of the most popular salmon species due to its meaty texture and quality protein. Oncorhynchus mykiss, which has a muscle texture similar to that of Salmo salar and is less expensive, is often used as a substitute for Salmo salar. As Salmo salar and Oncorhynchus mykiss belong to the same subfamily of Salmonidae, traditional methods are ineffective in the specific detection of the two. In this study, we combined hue-change with CRISPR/Cas12a lateral flow assay to detect the Salmo salar adulteration. This method detected S. salar genomic DNA at a vLOD of 5 copies, and was able to accurately identify adulterated samples containing 5 % w/w Salmo salar within one hour. In addition, the detection of Salmo salar in processed food products was achieved with the naked-eye at a concentration range of 0 % âˆ¼ 70 % w/w, and the detection accuracy is between 93.3 % âˆ¼ 100 %.

Engineering Carrier Density and Effective Mass of Plasmonic TiN Films by Tailoring Nitrogen Vacancies.

The introduction of nitrogen vacancies has been shown to be an effective way to tune the plasmonic properties of refractory titanium nitrides. However, its underlying mechanism remains debated due to the lack of high-quality single-crystalline samples and a deep understanding of electronic properties. Here, a series of epitaxial titanium nitride films with varying nitrogen vacancy concentrations (TiNx) were synthesized. Spectroscopic ellipsometry measurements revealed that the plasmon energy could be tuned from 2.64 eV in stoichiometric TiN to 3.38 eV in substoichiometric TiNx. Our comprehensive analysis of electrical and plasmonic properties showed that both the increased electronic states around the Fermi level and the decreased carrier effective mass due to the modified electronic band structures are responsible for tuning the plasmonic properties of TiNx. Our findings offer a deeper understanding of the tunable plasmonic properties in epitaxial TiNx films and are beneficial for the development of nitride plasmonic devices.

Identification of the shared gene MXD3 signatures and biological mechanism in patients with hip pain and prostate cancer.

Prostate cancer (PRAD) is recognized as having a significant effect on systemic illnesses. This study examined possible immune cells, metabolic pathways, and genes that may explain the interaction between PRAD and hip pain. We used information retrieved from the Cancer Genome Atlas and the Gene Expression Omnibus databases. To find common genes, we utilized differential expression analysis and weighted gene co-expression network analysis. The genes that were shared were subjected to pathway enrichment studies using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Additionally, hub genes were analyzed using LASSO regression, and a receiver operating characteristic curve was generated based on the screening outcomes. The genes for the nodes were chosen in a protein-protein interaction network that was built. Single-sample gene-set enrichment analysis was performed to identify the differentially expressed genes. Immunohistochemistry staining confirmed hub gene expression, and single-sample gene-set enrichment analysis assessed immune cell infiltration. We concluded by comparing MAX dimerization protein 3 (MXD3) and MAX interactor 1 (MXI1) expression in tumor tissues using Uniform Manifold Approximation and Projection and violin plots in the Tumor lmmune Single-cell Hub database. After analyzing the intersection of the differentially expressed genes and weighted gene co-expression network analysis-significant module genes, we determined that MXD3 was the best shared diagnostic biomarker for PRAD and hip pain. One potential predictor of PRAD development was the MXI1 node gene, which was found in the protein-protein interaction network. The analyses revealed that MXD3 had a relatively positive correlation with neutrophil and T-helper cell infiltration levels, whereas MXI1 had a negative correlation with mast and Tgd cell levels. Tumors had lower levels of MXI1 expression and higher levels of MXD3 expression compared to normal tissues. Endothelial cells, induced pluripotent stem cells, and smooth muscle cells were all found to express MXI1. This is the first study to investigate the close genetic link between hip pain and PRAD using bioinformatics technologies. The 2 most significant genes involved in crosstalk between PRAD and hip pain were MXD3 and MXI1. The immunological responses triggered by T cells, mast cells, and neutrophils may be crucial in the relationship between PRAD and hip pain.

Improved diagnostic efficiency of CRC subgroups revealed using machine learning based on intestinal microbes.

BACKGROUND: Colorectal cancer (CRC) is a common cancer that causes millions of deaths worldwide each year. At present, numerous studies have confirmed that intestinal microbes play a crucial role in the process of CRC. Additionally, studies have shown that CRC can be divided into several consensus molecular subtypes (CMS) based on tumor gene expression, and CRC microbiomes have been reported related to CMS. However, most previous studies on intestinal microbiome of CRC have only compared patients with healthy controls, without classifying of CRC patients based on intestinal microbial composition. RESULTS: In this study, a CRC cohort including 339 CRC samples and 333 healthy controls was selected as the discovery set, and the CRC samples were divided into two subgroups (234 Subgroup1 and 105 Subgroup2) using PAM clustering algorithm based on the intestinal microbial composition. We found that not only the microbial diversity was significantly different (Shannon index, p-value < 0.05), but also 129 shared genera altered (p-value < 0.05) between the two CRC subgroups, including several marker genera in CRC, such as Fusobacterium and Bacteroides. A random forest algorithm was used to construct diagnostic models, which showed significantly higher efficiency when the CRC samples were divided into subgroups. Then an independent cohort including 187 CRC samples (divided into 153 Subgroup1 and 34 Subgroup2) and 123 healthy controls was chosen to validate the models, and confirmed the results. CONCLUSIONS: These results indicate that the divided CRC subgroups can improve the efficiency of disease diagnosis, with various microbial composition in the subgroups.

Asymptomatic multicentric Castleman disease: A potential early stage of idiopathic MCD.

According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46.5 months (range: 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range: 3-60 months). During follow-up, 7 patients died; three of them died from progression of MCD. Despite that 37.7% patients received systemic treatment targeting MCD, this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all aMCD patients was 94.1% (95% CI 88.8-99.6%). Transformation to iMCD was an important predictor of death (log-rank p=0.01) (5-year estimated survival 83.3%). This study suggests that aMCD patients may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored.

Continuum percolation of two-dimensional adaptive dynamics systems.

The percolation phase transition of a continuum adaptive neuron system with homeostasis is investigated. In order to maintain their average activity at a particular level, each neuron (represented by a disk) varies its connection radius until the sum of overlapping areas with neighboring neurons (representing the overall connection strength in the network) has reached a fixed target area for each neuron. Tuning the two key parameters in the model, i.e., the density defined as the number of neurons (disks) per unit area and the sum of the overlapping area of each disk with its adjacent disks, can drive the system into the critical percolating state. These two parameters are inversely proportional to each other at the critical state, and the critical filling factors are fixed about 0.7157, which is much less than the case of the continuum percolation with uniform disks. It is also confirmed that the critical exponents in this model are the same as the two-dimensional standard lattice percolation. Although the critical state is relatively more sensitive and exhibits long-range spatial correlation, local fluctuations do not propagate in a long-range manner through the system by the adaptive dynamics, which renders the system overall robust against perturbations.

Identification of wheat stripe rust inoculum sources and dispersal routes responsible for initial rust establishment in southern Henan of China.

Wheat stripe rust (yellow rust), caused by Puccinia striiformis f. sp. tritici (Pst), is an important airborne disease worldwide. Pst inoculum strength in southern Henan in winter or early spring is important for spring epidemic in the main autumn-sown wheat-growing regions of China. However, there is limited knowledge about the source and time of initial infection on winter wheat in southern Henan. The first occurrence of wheat stripe rust in southern Henan was recorded annually from 2011-2022, from which we used the backward trajectory approach to infer the likely source of Pst inoculum responsible for the initial disease occurrence. The results suggested that the Pst inoculum responsible for initial rust established in the winter in southern Henan originated from the Gansu Pst oversummering area in China, whereas it originated from the adjacent winter Pst sporulation regions in southern Shaanxi and northwestern Hubei if Pst symptoms were first observed in early spring in southern Henan. Another possible Pst source is southern Hubei where Pst can also sporulate in the winter. Thus, early Pst development in winter in the main wheat production in China (Henan) is likely to be caused by Pst inoculum spread from the oversummering inocula or Pst epidemics in autumn seedlings in Gansu.

Clinical significance of positive resection margin for patients with rectal neuroendocrine tumors within 20 mm following initial endoscopic resection: A multi-center study.

BACKGROUND: The incidence of rectal neuroendocrine tumors (RNETs) has witnessed a significant surge, with a notable proportion being amenable to endoscopic removal. However, the clinical significance of positive resection margin for RNETs patients following endoscopic resection remain unknown, resulting in a lack of consensus regarding the appropriateness of implementing salvage treatment. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of individuals who underwent endoscopic resection for RNETs and classified them into two groups: the positive resection margin and the negative resection margin group. The overall survival (OS) and disease-free survival (DFS) were compared among two group. The independent variables were identified using univariate and multivariate logistic regression analyses to predict positive resection margin. Then, the model was established to predict the patients with positive resection margin using multivariate logistic regression. RESULTS: 181 RNETs patients (34.3 %) represented positive margin after endoscopic resection. Following a median follow-up period of 72 months, tumor recurrence manifested in 12 out of 527 patients (2.2 %) and the presence of positive resection margin was associated with worse DFS. Independent factors correlating with positive resection margin included endoscopic resection method choice, RNETs located in the low rectum, NLR >4.44 and tumor size exceeding 14.89 mm. A prediction model was therefore established with high predictive accuracy and excellent clinical applicability determined by calibration curves and DCA curve. Among RNETs patients with positive margin following endoscopic resection, implementing salvage treatment was beneficial for improving DFS and salvage endoscopic resection offer equal efficiency compared with salvage radical resection. CONCLUSIONS: Positive resection margin following endoscopic resection may indicate negative prognosis. Salvage treatment can improve the prognosis of RNETs patients with positive resection margin. Notably, salvage local resection exhibited similar efficacy compared with radical surgery in term of survival benefit.

Construction of platelet count-optical method reflex test rules using Micro-RBC#, Macro-RBC%, "PLT clumps?" flag, and "PLT abnormal histogram" flag on the Mindray BC-6800plus hematology analyzer in clinical practice.

OBJECTIVES: Utilizing RBC or PLT-related parameters to establish rules for the PLT-O reflex test can assist laboratories in quickly identifying specimens with interfered PLT-I that require PLT-O retesting. METHODS: Prospective PLT-I and PLT-O testing was performed on 6857 EDTA-anticoagulated whole blood samples, split randomly into training and validation cohorts at a 2:3 ratio. Reflex and non-reflex groups were distinguished based on the differences between PLT-I and PLT-O results. By comparing RBC and PLT parameter differences and flags in the training set, we pinpointed factors linked to PLT-O reflex testing. Utilizing Lasso regression, then refining through univariate and multivariate logistic regression, candidate parameters were selected. A predictive nomogram was constructed from these parameters and subsequently validated using the validation set. ROC curves were also plotted. RESULTS: Significant differences were observed between the reflex and non-reflex groups for 19 parameters including RBC, MCV, MCH, MCHC, RDW-CV, RDW-SD, Micro-RBC#, Micro-RBC%, Macro-RBC#, Macro-RBC%, MPV, PCT, P-LCC, P-LCR, PLR,"PLT clumps?" flag, "PLT abnormal histogram" flag, "IDA Anemia?" flag, and "RBC abnormal histogram" flag. After further analysis, Micro-RBC#, Macro-RBC%,"PLT clumps?", and "PLT abnormal histogram" flag were identified as candidate parameters to develop a nomogram with an AUC of 0.636 (95 %CI: 0.622-0.650), sensitivity of 42.9 % (95 %CI: 37.8-48.1 %), and specificity of 90.5 % (95 %C1: 89.6-91.3 %). CONCLUSIONS: The established rules may help laboratories improve efficiency and increase accuracy in determining platelet counts as a supplement to ICSH41 guidelines.

Seasonal biogenic volatile organic compound emission factors in temperate tree species: Implications for emission estimation and ozone formation.

Variability in biogenic volatile organic compound (BVOC) emissions across species and seasons poses challenges for accurate regional emission estimates and effective ozone (O3) control policies. To address this issue, we conducted in-situ measurements of emission factors for six dominant tree species in Beijing across four seasons. Subsequently, we developed monthly dynamic standard emission factors (SER-MDs) to model monthly BVOC emissions and their impacts on O3 formation at citywide and district levels. Our observations revealed pronounced seasonal differences in the BVOC composition and emission rates, as well as their responsiveness to monthly average temperature. By introducing the SER-MDs, we estimated BVOC emissions from the dominant tree species in Beijing to be 38.2 Gg yr-1, with monoterpenes and isoprene contributing 49% and 11%, respectively. This calculation reduced the overestimation associated with constant standard emission factors by 31%-38% at district level. The estimates also revealed regional differences in plant compositions rather than simple feedback from regional temperature and photosynthetically active radiation periods. Under these conditions, the maximum monthly BVOC-induced O3 concentration occurred in August and ranged from 4 to 17 µg m-3 across districts, with isoprene being the dominant contributor. Quercus mongolica and Populus tomentosa played significant roles in the formation of BVOC-induced O3 due to their strong isoprene emitting potential in July-August. These results indicate the necessity of introducing species-specific rhythms of BVOC emissions from dominant species in the development of urban BVOC emission inventories. This approach could inform the development of air pollution management policies that are consistent with the local vegetation composition and O3 pollution characteristics. For Beijing and other similar northern cities, reducing the use of tree species emitting substantial amounts of isoprene during periods of regional peak ambient O3 concentrations could constitute an effective nature-based solution for improving urban air quality in the future.

Essential phage component induces resistance of bacterial community.

Despite extensive knowledge on phage resistance at bacterium level, the resistance of bacterial communities is still not well-understood. Given its ubiquity, it is essential to understand resistance at the community level. We performed quantitative investigations on the dynamics of phage infection in Klebsiella pneumoniae biofilms. We found that the biofilms quickly developed resistance and resumed growth. Instead of mutations, the resistance was caused by unassembled phage tail fibers released by the phage-lysed bacteria. The tail fibers degraded the bacterial capsule essential for infection and induced spreading of capsule loss in the biofilm, and tuning tail fiber and capsule levels altered the resistance. Latent infections sustained in the biofilm despite resistance, allowing stable phage-bacteria coexistence. Last, we showed that the resistance exposed vulnerabilities in the biofilm. Our findings indicate that phage lysate plays important roles in shaping phage-biofilm interactions and open more dimensions for the rational design of strategies to counter bacteria with phage.

Patient-reported outcome measures for medication treatment satisfaction: a systematic review of measure development and measurement properties.

BACKGROUND: Medication Treatment Satisfaction (M-TS) from the patients' perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps. METHODS: Using PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM ). RESULTS: This review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test-retest reliability, results in 24 provided evidence of satisfactory test-retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability. CONCLUSIONS: Most existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS.

Altered purine and pentose phosphate pathway metabolism in uteroplacental insufficiency-induced intrauterine growth restriction offspring rats impair intestinal function.

This study aimed to identify metabolic alterations in the small intestine of newborn rats with intrauterine growth restriction (IUGR), a condition linked to intestinal dysfunction. Pregnant Sprague Dawley rats underwent bilateral uterine artery ligation on gestational day 17 to induce intrauterine growth restriction or sham surgery. Rat pups were delivered spontaneously on gestational day 22. Small intestine tissues were collected on postnatal days 0 and 7 from offspring. Liquid chromatography-mass spectrometry analysis was performed to investigate untargeted metabolomic profiles. Western blot analysis assessed protein expression of key regulators. Newborn rats with intrauterine growth restriction exhibited distinct small intestine metabolic profiles compared to controls on postnatal day 0. Notably, significant alterations were observed in purine metabolism, the pentose phosphate pathway, and related pathways. Western blot analysis revealed a decrease expression in transketolase, a key enzyme of the pentose phosphate pathway, suggesting impaired activity of the pentose phosphate pathway. Additionally, decreased expression of tight junction proteins ZO-1 and occludin indicated compromised intestinal barrier function in rats with intrauterine growth restriction. Similar metabolic disruptions persisted on postnatal day 7, with further reductions in tricarboxylic acid cycle intermediates and folate biosynthesis precursors. Interestingly, lysyl-glycine, a protein synthesis marker, was elevated in rats with intrauterine growth restriction. Our findings reveal a distinct metabolic signature in the small intestine of neonatal rats with intrauterine growth restriction, characterized by disruptions in the pentose phosphate pathway, purine metabolism, and energy production pathways. These novel insights suggest potential mechanisms underlying IUGR-associated intestinal dysfunction and impaired growth.

The interrelationships of CSF sTREM2, AD pathology, minimal depressive symptoms, and cognition in non-demented adults.

BACKGROUND: Microglial activation has been suggested to be involved in the pathogenesis of depression and Alzheimer's disease (AD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a marker of microglial activation. The purpose of this study was to investigate the interrelationships of cerebrospinal fluid (CSF) sTREM2, AD pathology, as well as minimal depressive symptoms (MDSs), and cognition. METHODS: A total of 545 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative cohort were included in our study. The average age of the total population was 72.6 years and the percentage of females was 42.6%. Linear regression models were conducted to investigate the linear relationships of MDSs with CSF sTREM2, AD pathology, cognition, and brain structure. Mediation models and structural equation models (SEM) were conducted to examine whether CSF sTREM2 mediated the relationships of MDSs with AD pathology and cognition. RESULTS: Results revealed that individuals with MDSs had lower CSF sTREM2 levels than normal controls. Linear regression showed that MDSs were linearly associated with CSF sTREM2 (PFDR = 0.012) and amyloid biomarkers (PFDR < 0.05), as well as cognitive scores (PFDR < 0.05) and hippocampal volume (PFDR = 0.003). Mediation analyses revealed that CSF sTREM2 mediated the association between MDSs and amyloid pathology, with the mediating proportions ranging from 6.030 to 18.894%. However, SEM failed to reveal that MDS affected cognition through CSF amyloid pathology and CSF sTREM2. CONCLUSIONS: MDSs are associated with amyloid pathology and cognition. CSF sTREM2 may potentially be an intervenable target between depression and AD pathology.

Risk factors for cognitive decline in non-demented elders with amyloid-beta positivity.

BACKGROUND: As a currently incurable but preventable disease, the prevention and early diagnosis of Alzheimer's disease (AD) has long been a research hotspot. Amyloid deposition has been shown to be a major pathological feature of AD. Notably, not all the people with amyloid-beta (Aß) pathology will have significant cognitive declines and eventually develop AD. Therefore, the aim of this study was to explore the risk factors for cognitive decline in Aß-positive participants. METHODS: We included 650 non-demented participants who were Aß-positive at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Mixed effects and COX regression models were applied to assess 37 potential risk factors. Mixed effects models were employed to assess the temporal associations between potential risk factors and four cognitive assessment scales. COX regression models were used to assess the impact of potential risk factors on cognitive diagnosis conversion. Univariate and multivariate analyses were applied to the above models. Additionally, we used the Cochran-Armitage trend test to examine whether the incidence of cognitive decline increased with the number concurrent of risk factors. RESULTS: Six factors (low diastolic pressure, low body mass index, retired status, a history of drug abuse, Parkinsonism, and depression) were the identified risk factors and four factors (a history of urinary disease, musculoskeletal diseases, no major surgical history, and no prior dermatologic-connective tissue diseases) were found to be suggestive risk factors. The incidence of cognitive decline in the Aß-positive participants gradually increased as the number of concurrent risk factors increased (p for trend = 0.0005). CONCLUSIONS: Our study may facilitate the understanding of the potential pathological processes in AD and provide novel targets for the prevention of cognitive decline among participants with Aß positivity.

Postoperative urinary retention following transanal versus laparoscopic total mesorectal excision for rectal cancer: A randomized trial report from an experienced center.

Background: Transanal total mesorectal excision has emerged as a potential solution to certain limitations associated with laparoscopic total mesorectal excision in rectal cancer patients. Differences in surgical approaches have raised questions regarding their impact on the risk of postoperative urinary retention, with limited data available from large scale randomized clinical study. Objective: To report incidence of postoperative urinary retention and evaluate the associated risk factors for transanal total mesorectal excision. Design: In this randomized controlled trial (ClinicalTrials. gov NCT06147492), we retrieved 524 patients who received total mesorectal excision (TME) for stage I-III rectal cancer between June 2019 and April 2022, and the patients were randomly assigned in a 1:1 ratio to undergo either taTME or laTME. Patients: We enrolled 524 patients who underwent total mesorectal excision for stage I-III rectal cancer between June 2019 and April 2022. Main outcome measures: The incidence of postoperative urinary retention. Results: Among the 524 enrolled patients, 261 were randomized to the laTME group, while 263 were were randomized the taTME group. The median age was 58 years, and 340 participants (64.8 %) were male. Notably, 37 individuals (7.0 %) experienced postoperative urinary retention during the follow-up period, with no significant disparity was observed between the taTME and laTME groups (6.8 % and 7.2 %, respectively, P = 0.98). Risk factors associated with PUR in patients following taTME encompassed early removal of the urinary catheter (P = 0.006), net infusion rate >4.09 ml kg-1.h-1 (P = 0.006), and an age surpassing 65 years (P = 0.0321). Limitations: The generalizability of the findings outside specialist rectal cancer centers may be limited. Conclusions: Transanal total mesorectal excision was not found to heighten the risk of postoperative urinary retention. Nonetheless, it is advisable removing postoperative catheter beyond the initial day and exercising caution in the administration of intravenous fluids in clinical practice for taTME procedures.

Ability of detection in different resolution endoscopy for upper gastrointestinal mucosal lesions.

BACKGROUND: Most endoscopists believe that higher resolution improves lesion detection rates. However, existing studies primarily compared the detection rates of white light endoscopy (WLE) and other imaging modalities. Our previous study demonstrated the advantages of magnifying endoscopy from general endoscopy for lesion detection, prompting further investigation into the variations in lesion detection rates across endoscopes with different resolutions. METHODS: Endoscopic and corresponding pathological data from our medical unit over the past 5 years were analyzed. We excluded specific-purpose endoscopic procedures to ensure the natural randomization of the data. Baseline adjustment and risk factor analyses used multi-group propensity score matching and logistic regression. RESULTS: The overall lesion detection rate was significantly higher with high-quality endoscopy (Q-endoscopy) compared to high-definition endoscopy (H-endoscopy) and high definition and quality endoscopy (HQ-endoscopy) (34.4% vs. 30.2% vs. 29.6%, P = 0.001). Similar results were observed for elevated lesions (25.7% vs. 21.0% vs. 22.9%, P = 0.001) and depressed lesions (6.6% vs. 6.2% vs. 3.6%, P < 0.001). HQ-endoscopy had a superior detection rate for superficial lesions compared to both H- and Q-endoscopies (3.0% vs. 2.8% vs. 1.8%, P = 0.041). However, there were no significant differences in neoplastic detection rate or missed neoplastic lesion rate among the three groups. CONCLUSION: Q-endoscopy is superior in detecting non-superficial lesions, while HQ-endoscopy is better at detecting superficial lesions. However, there were no statistically significant differences in detecting or omitting neoplastic lesions among the three endoscopic examinations.

Deoxyshikonin: a promising lead drug grass against drug resistance or sensitivity to Helicobacter pylori in an acidic environment.

Helicobacter pylori (H. pylori) is closely associated with the diseases such as gastric sinusitis, peptic ulcers, and gastric adenocarcinoma. Its drug resistance is very severe, and new antibiotics are urgently needed. Nine comfrey compounds were screened by antimicrobial susceptibility testing, among which deoxyshikonin had the best inhibitory effect, with a minimum inhibitory concentration (MIC) of 0.5-1 µg/mL. In addition, deoxyshikonin also has a good antibacterial effect in an acidic environment, it is highly safe, and H. pylori does not readily develop drug resistance. Through in vivo experiments, it was proven that deoxyshikonin (7 mg/kg) had a beneficial therapeutic effect on acute gastritis in mice infected with the multidrug-resistant H. pylori BS001 strain. After treatment with desoxyshikonin, colonization of H. pylori in the gastric mucosa of mice was significantly reduced, gastric mucosal damage was repaired, inflammatory factors were reduced, and the treatment effect was better than that of standard triple therapy. Therefore, deoxyshikonin is a promising lead drug to solve the difficulty of drug resistance in H. pylori, and its antibacterial mechanism may be to destroy the biofilm and cause an oxidation reaction.

Targeted agents plus CHOP compared with CHOP as the first-line treatment for newly diagnosed patients with peripheral T-cell lymphoma (GUIDANCE-03): an open-label, multicentre phase 2 clinical trial.

Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. We conducted an open-label, phase 2 nonrandomised, externally controlled study to evaluate the efficacy and safety of targeted agents plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) (CHOPX) for PTCL in the front-line setting. Methods: Eligible patients were ≥18 years of age and newly diagnosed PTCL. Patients in the CHOPX group received standard CHOP at Cycle 1. Specific targeted agents were added from Cycle 2, decitabine if TP53 mut, azacytidine if TET2/KMT2D mut, tucidinostat if CREBBP/EP300 mut, and lenalidomide if without mutations above. Patients in the CHOP group received CHOP for 6 cycles. The primary endpoint was the complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov, NCT04480099. Findings: Between July 29, 2020, and Sep 22, 2022, 96 patients were enrolled and included for efficacy and safety analysis with 48 in each group. The study met its primary endpoint. CRR at EOT in the CHOPX group was superior to the CHOP group (64.6% vs. 33.3%, OR 0.27, 95%CI 0.12-0.64; p = 0.004). At a median follow-up of 24.3 months (IQR 12.0-26.7), improved median PFS was observed in the CHOPX group (25.5 vs. 9.0 months; HR 0.57, 95%CI 0.34-0.98; p = 0.041). The median OS was similar between two groups (not reached vs. 30.9 months; HR 0.55, 95%CI 0.28-1.10; p = 0.088). The most common grade 3-4 hematological and non-hematological adverse events in the CHOPX group were neutropenia (31, 65%) and infection (5, 10%). Interpretation: Targeted agents combined with CHOP demonstrated effective and safe as first-line treatment in PTCL. Biomarker-driven therapeutic strategy is feasible and may lead to promising efficacy specifically toward molecular features in PTCL. Funding: This study was supported by the National Key Research and Development Program (2022YFC2502600) and the General Program of the Shanghai Municipal Health Commission (202040400).