Knowledge, attitudes, and practices of endoscopy among gastroenterologists in diagnosis and management of inflammatory bowel disease in China: a multicenter cross-sectional study.

BACKGROUND: The aim was to assess the knowledge, attitudes, and practices (KAPs) of endoscopy among gastroenterologists in the diagnosis and management of IBD in China. METHODS: A multicenter cross-sectional KAP study was performed. The questionnaire was developed and improved using feedback and opinions from a team of experienced IBD specialist professors and then distributed and collected online. In addition, eight fellow gastroenterologists participated in an IBD endoscopy training program were asked to review endoscopic images, and the consistency of the endoscopic scores before and after training was calculated. RESULTS: A total of 193 participants from 12 provincial-level administrative regions encompassing both the Northern and Southern parts of China completed the study questionnaire. The median age of the participants was 40 (36, 45) years, with the majority being female (70.5%). The median professional experience as gastroenterologists was 11 (7, 17) years, while the median experience as endoscopists was 8 (3, 15) years. The median knowledge score was 8 out of 10 points for single-choice questions; however, most gastroenterologists believed that some concepts in these endoscopic indices were vague, including those regarding deep ulcerations, ulcerated surfaces, affected surfaces and narrowing in open-answer questions. The UCEIS and SES-CD were considered most consistent with clinical activity score in the evaluation of UC and CD, respectively. IBD subspecialists and gastroenterologists who had previously received IBD endoscopy screening training were more likely to use endoscopic indices (p<0.001, p = 0.029, respectively). The Rutgeerts score demonstrated the most significant improvement in consistency before and after training, from 0.407 (95% CI: 0.025-0.999) to 0.909 (95% CI: 0.530-1.000). CONCLUSIONS: We propose the elucidation of ambiguous definitions in endoscopic indices, enhancement of training, and the application of innovative technology to enhance the application of endoscopic evaluation and endoscopic indices in clinical practice.

First Report of Colletotrichum spaethianum Causing Anthracnose on Jiaotou (Allium chinense G. Don) in China.

Jiaotou (Allium chinense G. Don) is a culinary and aromatic herb belonging to the family Amaryllidaceae. It is native to China and cultivated for its culinary uses in many other countries, which also possess high medicinal value in traditional Chinese medicine (Rhetso et al. 2020). In March 2023, a disease resembling anthracnose was detected in the fields of Changde city, Hunan Province, China. The symptoms manifested as yellow to brown necrotic spots located at the tip or middle of the blade. The lesions tended to wrinkle, leading to leaf distortion, thinning, and wilting. This disease has a high incidence rate of approximately 50% in an area of nearly 20 hectares. Ten symptomatic plants were collected for pathogen isolation. The leaf tissues were surface sterilized using 70% ethyl alcohol and 2% sodium hypochlorite, rinsed with sterile distilled water, and then transferred to potato dextrose agar (PDA) and incubated at 26°C in the dark. Ten colonies with similar cultural morphology were selected from the 10 affected plant samples. The fungal strains produced densely aerial mycelium on PDA, displaying off-white to gray-brown coloration. Conidia were hyaline, curved or slightly curved, aseptate, with a rounded apex and truncate base, contained oil globules, and measuring 21.0 to 29.0 × 4.1 to 5.3 µm (n = 50. Appressoria were dark brown, irregular in shape, partially lobed, and measured 6.5 to 15.5 µm long × 5.0 to 10.5 µm wide. Setae were straight, dark brown, with two- to three-septate, 78.5 to 155.4 µm long (n = 50). These morphological characteristics were similar to Colletotrichum spaethianum (Damm et al. 2009). The internal transcribed spacer (ITS) region of rDNA, actin (ACT), chitin synthase (CHS-1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes of three representative strains, JT-1, JT-2 and JT-3, were amplified and sequenced as described in Weir et al. (2012). These sequences were 99 to 100% identical to corresponding sequences of C. spaethianum strains (565/569 bp, MN396364.1 for ITS; 565/569 bp, MN433299.1 for ACT; 262/263 bp, MN433298.1 for GAPDH; 272/272 bp, MH020773 for CHS-1, respectively) (Zhong et al. 2020; Liu et al. 2020; Sun et al. 2020). A concatenated phylogenetic tree showed that all three strains were clustered within the C. spaethianum clade. The sequences of isolate JT-1 were deposited in GenBank (accession nos. PP911453, PP911607, PP911605, and PP911606 for ITS, ACT, GAPDH and CHS-1, respectively). For pathogenicity assays, 1-month-old seedings of A. chinense in plots were inoculated by spraying with a conidial suspension (1 × 105 conidia/ml) until runoff. Control plants were sprayed with sterilized water. All the inoculated plants were kept in a greenhouse at 25°C with a 12-h/12-h light/dark cycle. The experiment was conducted twice with three replications each. After 7 days, symptoms similar to those observed in the field developed on leaves of the inoculated plants, whereas the control plants remained asymptomatic C. spaethianum was specifically reisolated and identified from the symptomatic leaves, thus fulfilling Koch's postulates. Colletotrichum spaethianum has been recorded as a pathogen fungus on many medicinal plants, such as Peucedanum praeruptorum (Guo et al. 2013), Anemarrhena asphodeloides (Okorley et al. 2019), and Paris polyphylla (Zhong et al. 2020). To our knowledge, this is the first report of C. spaethianum causing anthracnose on Jiaotou in China. Effective control measures should be implemented to mitigate potential further damage to Jiaotou cultivation.

Cell cycle checkpoint revolution: targeted therapies in the fight against malignant tumors.

Malignant tumors are among the most important causes of death worldwide. The pathogenesis of a malignant tumor is complex and has not been fully elucidated. Studies have shown that such pathogenesis is related to abnormal cell cycle progression. The expression levels of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors as well as functions of the cell cycle checkpoints determine whether the cell cycle progression is smooth. Cell-cycle-targeting drugs have the advantages of high specificity, low toxicity, low side effects, and low drug resistance. Identifying drugs that target the cell cycle and applying them in clinical treatments are expected to promote chemotherapeutic developments against malignant tumors. This article aims to review drugs targeted against the cell cycle and their action mechanisms.

Aspertaichamide B, a new anti-tumor prenylated indole alkaloid from the fungus Aspergillus japonicus TE-739D.

Prenylated indole alkaloids, which are mainly produced by genera Aspergillus and Penicillium, are a class of structurally intriguing specialized metabolites with remarkable biomedical interests. In this study, chemically guided isolation of the Nicotiana tabacum-derived endophytic fungus Aspergillus japonicus TE-739D yielded eight structurally diverse prenylated indole alkaloids, including an undescribed compound, namely aspertaichamide B (ATB, 1), together with seven previously discovered derivatives (compounds 2 - 8). Their chemical structures as well as the stereochemical features were determined by integrated spectroscopic analyses, including HRESIMS, NMR, NMR calculations with DP4 + probability analysis, and a comparison of the experimental ECD data with computed DFT-based quantum chemical calculations. In vitro cytotoxic effects against the gastric cancer MFC cells revealed that the new compound ATB demonstrated considerable activity. Further studies found that ATB suppressed the viability, colony formation, and migration ability of MFC cells, and induced MFC cells apoptosis in a concentration-dependent way. Moreover, ATB stimulated ROS production in MFC cells and inhibited the tumor growth in the MFC-sourced subcutaneous tumor model while not significantly reducing the weight of mice. The pharmacological results suggested that the newly discovered ATB may be a promising anti-tumor lead compound. KEY POINTS: • Eight structurally diverse prenylated indole alkaloids including a new aspertaichamide B (ATB) were isolated from the fungus Aspergillus japonicus TE-739D. • The structure of ATB was elucidated by HRESIMS, NMR, NMR calculations with DP4 + probability analysis, and ECD calculations. • ATB inhibited cell proliferation, promoted apoptosis, and increased ROS production in gastric cancer cells, and exhibited inhibitory effects on tumor growth in vivo.

Natural course of ulcerative colitis in China: Differences from the West?

BACKGROUND AND AIMS: Whether the natural course of ulcerative colitis (UC) in mainland China is similar or different from that in Western countries is unknown, and data on it is limited. We aimed to provide a comprehensive description of the natural course of UC in China and compare it with Western UC patients. METHODS: Based on a prospective Chinese nationwide registry of consecutive patients with inflammatory bowel diseases, the medical treatments and natural history of UC were described in detail, including disease extension, surgery, and neoplasia. The Cox regression model was used to identify factors associated with poor outcomes. RESULTS: A total of 1081 UC patients were included with a median follow-up duration of 5.3 years. The overall cumulative exposure was 99.1% to 5-aminosalicylic acids, 52.1% to corticosteroids, 25.6% to immunomodulators, and 15.4% to biologics. Disease extent at diagnosis was proctitis in 26.9%, left-sided colitis in 34.8%, and extensive colitis in 38.3%. Of 667 patients with proctitis and left-sided colitis, 380 (57.0%) experienced disease extent progression. A total of 58 (5.4%) UC patients underwent colectomy, demonstrating cumulative proportions of surgery at 1, 5, and 10 years after diagnosis of 0.6%, 3.4%, and 8.2%, respectively. In addition, 23 (2.1%) UC patients were diagnosed with neoplasia, demonstrating cumulative proportions of neoplasia at 1, 5, and 10 years after diagnosis of 0.5%, 1.0%, and 3.5%, respectively. CONCLUSIONS: Chinese UC patients had similar cumulative proportions of exposure to IBD-specific treatments but a lower surgical rate than patients in Western countries, indicating a different natural course, and close monitoring needs for UC in China. However, these results must be confirmed in population-based studies because the hospital-based cohort in our study might lead to selection bias.

Triterpene-Based Prodrug for Self-Boosted Drug Release and Targeted Oral Squamous Cell Carcinoma Chemotherapy.

Chemotherapy is one of the main treatments for oral squamous cell carcinoma (OSCC), especially as a combined modality approach with and after surgery or radiotherapy. Limited therapeutic efficiency and serious side effects greatly restrict the clinical performance of chemotherapeutic drugs. The development of smart nanomedicines has provided new research directions, to some extent. However, the involvement of complex carrier compositions inevitably brings biosafety concerns and greatly limits the "bench-to-bed" translation of most nanomedicines reported. In this study, a carrier-free self-assembled prodrug was fabricated by two triterpenes (glycyrrhetinic acid, GA and ginsenoside Rh2, Rh2) isolated from medicinal plants, licorice, and ginseng, for the targeted and highly effective treatment of OSCC. Reactive oxygen species (ROS) self-supplied molecule TK-GA2 was synthesized with ROS-responsive thioketal linker and prodrug was prepared by a rapid-solvent-exchange method with TK-GA2 and Rh2. After administration, oral tumor cells transported large amounts of prodrugs with glucose ligands competitively. Endogenous ROS in oral tumor cells then promoted the release of GA and Rh2. GA further evoked the generation of a large number of ROS to help self-boosted drug release and increase oxidative stress, synergistically causing tumor cell apoptosis with Rh2. Overall, this carrier-free triterpene-based prodrug might provide a preeminent opinion on the design of effective chemotherapeutics with low systemic toxicity against OSCC.

The performance and mechanism of sulfidated nano-zero-valent iron for the simultaneous stabilization of arsenic and cadmium.

Co-contamination of soil and groundwater with arsenic (As) and cadmium (Cd) is widespread. Sulfidized Nanoscale Zero-Valent Iron (S-nZVI) is effective in removing As and Cd from contaminated environments. However, the mechanisms governing As and Cd removal from systems containing both species are still unclear. This study investigated the effectiveness of S-nZVI in the simultaneous removal of Cd(II) and As(III) from contaminated solutions and their interaction mechanisms. Adsorption experiments were conducted under aerobic conditions to investigate the effect of Cd(II) and As(III) on their co-immobilisation at different As(III) and Cd(II) concentrations. S-nZVI was characterised before and after the reaction to elucidate the mechanism of its simultaneous immobilisation of As(III) and Cd(II). Batch experiments revealed that the presence of Cd(II) and As(III) together considerably promotes the passivation of S-nZVI. The adsorption of Cd(II) at Cd:As = 1:3 was 198.37 mg/g, which was 27.6 % higher than that in Cd(II)-only systems, and the adsorption of As(III) at As:Cd = 1:3 was 204.05 mg/g, which was 175 % higher than that in As(III)-only systems. The results of X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy indicated that the removal of Cd(II) and As(III) by S-nZVI involves electrostatic adsorption, complexation and oxidation reactions, amongst which electrostatic adsorption and ternary-complex generation are responsible for the synergistic effect. As and Cd ions can form two types of surface complexes with FeOH or FeS on the outer layer of S-nZVI: anionic bridging to form Fe-As-Cd and cationic bridging to form Fe-Cd-As. This investigation elucidates the synergistic action of Cd(II) and As(III) during their removal using S-nZVI. Thus, S-nZVI is a promising material for the combined removal of Cd(II) and As(III), which can mitigate environmental pollution.

Computer-aided molecular design and optimization of potent inhibitors disrupting APC‒Asef interaction.

Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. At initial diagnosis, approximately 20% of patients are diagnosed with metastatic CRC (mCRC). Although the APC‒Asef interaction is a well-established target for mCRC therapy, the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging endeavor. In this study, we identified a novel structural scaffold based on MAI inhibitors, the first-in-class APC‒Asef inhibitors we reported previously. ONIOM model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed, and 24-fold greater potency was obtained with the best inhibitor compared to the parental compound. In addition, the cocrystal structure validated that the two-layer π‒π stacking interactions were essential for inhibitor stabilization in the bound state. Furthermore, in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC‒Asef interaction. These results provide an intrinsic structural basis to further explore drug-like molecules for APC‒Asef-mediated CRC therapy.

Radiomic score for lung nodules as a prognostic biomarker in locally advanced rectal cancer patients: A bi-institutional study.

BACKGROUND: Undetermined lung nodules are common in locally advanced rectal cancer (LARC) and lack precise risk stratification. This study aimed to develop a radiomic-based score (Rad-score) to distinguish metastasis and predict overall survival (OS) in patients with LARC and lung nodules. METHODS: Retrospective data from two institutions (July 10, 2006-September 24, 2015) was used to develop and validate the Rad-score for distinguishing lung nodule malignancy. The prognostic value of the Rad-score was investigated in LARC cohorts, leading to the construction and validation of a clinical and radiomic score (Cli-Rad-score) that incorporates both clinical and radiomic information for the purpose of improving personalized clinical prognosis prediction. Descriptive statistics, survival analysis, and model comparison were performed to assess the results. RESULTS: The Rad-score demonstrated great performance in distinguishing malignancy, with C-index values of 0.793 [95% CI: 0.729-0.856] in the training set and 0.730 [95% CI: 0.666-0.874] in the validation set. In independent LARC cohorts, Rad-score validation achieved C-index values of 0.794 [95% CI: 0.737-0.851] and 0.747 [95% CI: 0.615-0.879]. Regarding prognostic prediction, Rad-score effectively stratified patients. Cli-Rad-score outperformed the clinicopathological information alone in risk stratification, as evidenced by significantly higher C-index values (0.735 vs. 0.695 in the internal set and 0.618 vs. 0.595 in the external set). CONCLUSIONS: CT-based radiomics could serve as a reliable and powerful tool for lung nodule malignancy distinction and prognostic prediction in LARC patients. Rad-score predicts prognosis independently. Incorporation of Cli-Rad-score significantly enhances the persionalized clinical prognostic capacity in LARC patients with lung nodules.

Ar/NH3 Plasma Etching of Cobalt-Nickel Selenide Microspheres Rich in Selenium Vacancies Wrapped with Nitrogen Doped Carbon Nanotubes as Highly Efficient Air Cathode Catalysts for Zinc-Air Batteries.

This work utilizes defect engineering, heterostructure, pyridine N-doping, and carbon supporting to enhance cobalt-nickel selenide microspheres' performance in the oxygen electrode reaction. Specifically, microspheres mainly composed of CoNiSe2 and Co9Se8 heterojunction rich in selenium vacancies (VSe·) wrapped with nitrogen-doped carbon nanotubes (p-CoNiSe/NCNT@CC) are prepared by Ar/NH3 radio frequency plasma etching technique. The synthesized p-CoNiSe/NCNT@CC shows high oxygen reduction reaction (ORR) performance (half-wave potential (E1/2) = 0.878 V and limiting current density (JL) = 21.88 mA cm-2). The JL exceeds the 20 wt% Pt/C (19.34 mA cm-2) and the E1/2 is close to the 20 wt% Pt/C (0.881 V). It also possesses excellent oxygen evolution reaction (OER) performance (overpotential of 324 mV@10 mA cm-2), which even exceeds that of the commercial RuO2 (427 mV@10 mA cm-2). The density functional theory calculation indicates that the enhancement of ORR performance is attributed to the synergistic effect of plasma-induced VSe· and the CoNiSe2-Co9Se8 heterojunction. The p-CoNiSe/NCNT@CC electrode assembled Zinc-air batteries (ZABs) show a peak power density of 138.29 mW cm-2, outperforming the 20 wt% Pt/C+RuO2 (73.9 mW cm-2) and other recently reported catalysts. Furthermore, all-solid-state ZAB delivers a high peak power density of 64.83 mW cm-2 and ultra-robust cycling stability even under bending.

A clade of receptor-like cytoplasmic kinases and 14-3-3 proteins coordinate inositol hexaphosphate accumulation.

Inositol hexaphosphate (InsP6) is the major storage form of phosphorus in seeds. Reducing seed InsP6 content is a breeding objective in agriculture, as InsP6 negatively impacts animal nutrition and the environment. Nevertheless, how InsP6 accumulation is regulated remains largely unknown. Here, we identify a clade of receptor-like cytoplasmic kinases (RLCKs), named Inositol Polyphosphate-related Cytoplasmic Kinases 1-6 (IPCK1-IPCK6), deeply involved in InsP6 accumulation. The InsP6 concentration is dramatically reduced in seeds of ipck quadruple (T-4m/C-4m) and quintuple (C-5m) mutants, accompanied with the obviously increase of phosphate (Pi) concentration. The plasma membrane-localized IPCKs recruit IPK1 involved in InsP6 synthesis, and facilitate its binding and activity via phosphorylation of GRF 14-3-3 proteins. IPCKs also recruit IPK2s and PI-PLCs required for InsP4/InsP5 and InsP3 biosynthesis respectively, to form a potential IPCK-GRF-PLC-IPK2-IPK1 complex. Our findings therefore uncover a regulatory mechanism of InsP6 accumulation governed by IPCKs, shedding light on the mechanisms of InsP biosynthesis in eukaryotes.

The CfKOB1 gene related to cell apoptosis is required for pathogenicity and involved in mycovirus-induced hypovirulence in Colletotrichum fructicola.

Colletotrichum fructicola is a globally significant phytopathogenic fungus. Mycovirus-induced hypovirulence has great potential for biological control and study of fungal pathogenic mechanisms. We previously reported that the mycovirus Colletotrichum alienum partitivirus 1 (CaPV1) is associated with the hypovirulence of C. fructicola, and the present study aimed to further investigate a host factor and its roles in mycovirus-induced hypovirulence. A gene named CfKOB1, which encodes putative protein homologous to the ß-subunit of voltage-gated potassium channels and aldo-keto reductase, is downregulated upon CaPV1 infection and significantly upregulated during the early infection phase of Nicotiana benthamiana by C. fructicola. Deleting the CfKOB1 gene resulted in diminished vegetative growth, decreased production of asexual spores, hindered appressorium formation, reduced virulence, and altered tolerance to abiotic stresses. Transcriptome analysis revealed that CfKOB1 regulates many metabolic pathways as well as the cell cycle and apoptosis. Furthermore, enhanced apoptosis was observed in the ΔCfKOB1 mutants. Viral RNA accumulation was significantly increased in the CfKOB1 deletion mutant. Additionally, our findings demonstrated that CaPV1 infection in the WT strain also induced cell apoptosis. Collectively, these results highlight the diverse biological roles of the CfKOB1 gene in the fungus C. fructicola, while it also participates in mycovirus-induced hypovirulence by regulating apoptosis.

MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases.

Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven to be an effective local treatment modality but incompetent against metastases. Hence, the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a magnetic resonance imaging (MRI)-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with a programmed cell death 1 (PD-1) inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under an 808 nm near-infrared laser. In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with an 808-nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP non-invasively due to the presence of superparamagnetic iron oxide nanocrystal in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32°C to 60.7°C in 5 min. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided PTT/PDT results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.

The LRR receptor-like kinase ALR1 is a plant aluminum ion sensor.

Plant survival requires an ability to adapt to differing concentrations of nutrient and toxic soil ions, yet ion sensors and associated signaling pathways are mostly unknown. Aluminum (Al) ions are highly phytotoxic, and cause severe crop yield loss and forest decline on acidic soils which represent ∼30% of land areas worldwide. Here we found an Arabidopsis mutant hypersensitive to Al. The gene encoding a leucine-rich-repeat receptor-like kinase, was named Al Resistance1 (ALR1). Al ions binding to ALR1 cytoplasmic domain recruits BAK1 co-receptor kinase and promotes ALR1-dependent phosphorylation of the NADPH oxidase RbohD, thereby enhancing reactive oxygen species (ROS) generation. ROS in turn oxidatively modify the RAE1 F-box protein to inhibit RAE1-dependent proteolysis of the central regulator STOP1, thus activating organic acid anion secretion to detoxify Al. These findings establish ALR1 as an Al ion receptor that confers resistance through an integrated Al-triggered signaling pathway, providing novel insights into ion-sensing mechanisms in living organisms, and enabling future molecular breeding of acid-soil-tolerant crops and trees, with huge potential for enhancing both global food security and forest restoration.

A Convenient and Effective Preoxygenation Technique for Prolonging Deep Inspiration Breath-Hold Duration With a Venturi Mask With a 50% Oxygen Concentration.

PURPOSE: Voluntary deep inspiration breath-hold (DIBH) is commonly used in radiation therapy (RT), but the short duration of a single breath-hold, estimated to be around 20 to 40 seconds, is a limitation. This prospective study aimed to assess the feasibility and safety of using a simple preoxygenation technique with a Venturi mask to prolong voluntary DIBH. METHODS AND MATERIALS: The study included 33 healthy volunteers and 21 RT patients. Preoxygenation was performed using a Venturi mask with a 50% oxygen concentration. Paired t tests compared the duration of a single DIBH in room air and after 5, 15, and 30 minutes of preoxygenation in healthy volunteers. Sustainability of breath-hold and tolerability of heart rate and blood pressure were assessed for multiple DIBH durations in both volunteers and patients. RESULTS: In healthy volunteers, a 15-minute preoxygenation significantly prolonged the duration of a single DIBH by 24.95 seconds compared with 5-minute preoxygenation (89 ± 27.76 vs 113.95 ± 30.63 seconds; P < .001); although there was a statistically significant increase in DIBH duration after 30-minute preoxygenation, it was only extended by 4.95 seconds compared with 15-minute preoxygenation (113.95 ± 30.63 vs 118.9 ± 29.77 seconds; P < .01). After 15-minute preoxygenation, a single DIBH lasted over 100 seconds in healthy volunteers and over 80 seconds in RT patients, with no significant differences among 6 consecutive cycles of DIBH. Furthermore, there were no significant differences in heart rate or blood pressure after DIBHs, including DIBH in room air and 6 consecutive DIBHs after 15-minute preoxygenation (all P > .05). CONCLUSIONS: Preoxygenation with a 50% oxygen concentration for 15 minutes effectively prolongs the duration of 6 cycles of DIBH both in healthy volunteers and RT patients. The utilization of a Venturi mask to deliver 50% oxygen concentration provides a solution characterized by its convenience, good tolerability, and effectiveness.

An interpretable model predicts visual outcomes of no light perception eyes after open globe injury.

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.

Characterization and biocontrol mechanism of Streptomyces olivoreticuli as a potential biocontrol agent against Rhizoctonia solani.

Rhizoctonia solani is a widespread and devastating plant pathogenic fungus that infects many important crops. This pathogen causes tobacco target spot, a disease that is widespread in many tobacco-growing countries and is destructive to tobacco. To identify antagonistic microorganisms with biocontrol potential against this disease, we isolated Streptomyces strains from forest inter-root soil and screened a promising biocontrol strain, ZZ-21. Based on in vitro antagonism assays, ZZ-21 showed a significant inhibitory effect on R. solani and various other phytopathogens. ZZ-21 was identified as Streptomyces olivoreticuli by its phenotypic, genetic, physiological and biochemical properties. Complete genome sequencing revealed that ZZ-21 harbored numerous antimicrobial biosynthesis gene clusters. ZZ-21 significantly reduced the lesion length in detached inoculated leaf assays and reduced the disease index under greenhouse and field conditions. Based on an in vitro antagonistic assay of ZZ-21 culture, the strain exhibited an antifungal activity against R. solani in a dose-dependent manner. The culture filtrate could impair membrane integrity, possibly through membrane lipid peroxidation. ZZ-21 could secrete multiple extracellular enzymes and siderophores. According to a series of antifungal assays, the extracellular metabolites of ZZ-21 contained antimicrobial bioactive compounds composed of proteins/peptides extracted using ammonium sulfate precipitation, which were stable under stress caused by high temperature and protease K. The EC50 value for ammonium sulfate precipitation was determined to be 21.11 µg/mL in this study. Moreover, the proteins/peptides also exhibited biocontrol ability and were observed to alter the plasma membrane integrity of R. solani which were evaluated by biocontrol efficacy assays on detached tobacco leaves and PI staining. Overall, strain ZZ-21 shows the potential to be developed into a biopesticide against tobacco target spot disease.

Geographical heterogeneity in the disease characteristics and management of patients with inflammatory bowel disease, the preliminary results of a Chinese database for IBD (CHASE-IBD).

Background: The incidence of inflammatory bowel disease (IBD) is rapidly increasing in China, a vast country with significant geographical differences. The socioeconomic status of Eastern China is significantly higher than that of Western China. Objectives: This study aimed to describe the geographical heterogeneity in the characteristics and management of patients with IBD in both Eastern and Western China. Design: This was a multicenter, cross-sectional study. Methods: Patients with IBD with ages ⩾18 years up to 18 January 2023 were included in the analysis from the Chinese database for IBD. Logistic regression was used to identify risk factors associated with surgeries among patients with IBD. Results: Among 8305 patients with IBD, the ratio of ulcerative colitis (UC) to Crohn's disease (CD) was 4.13 and 0.33 in Western and Eastern China, respectively. The median age at diagnosis of UC and CD was 40.69 and 28.58 years, respectively. There was a male predominance among patients with UC (54.3%) and CD (68.0%). The two regions exhibited a similar distribution of disease locations in UC. However, Western China had a higher proportion of L2 involvement (30.0% versus 19.1%) and more advanced disease behavior (B2 and B3) (48.8% versus 39.8%) than Eastern China. Patients with IBD in Western China received more 5-aminosalicylic acid and corticosteroids and fewer immunomodulators and biologicals. In terms of surgical risk, Eastern China [versus Western China, odds ratios (OR): 5.36, 95% confidence intervals (CI): 2.96-9.68] was associated with a higher risk of surgery in UC, while Western China (versus Eastern China, OR: 3.39, 95% CI: 2.37-4.86) was associated with a higher risk of surgery in CD. Conclusion: Geographical heterogeneity exists in the disease characteristics and management of IBD in Eastern and Western China. These findings have the potential to guide the formulation of location-specific strategies aimed at enhancing the long-term outcomes of patients with IBD.

Interactions among acute respiratory viruses in Beijing, Chongqing, Guangzhou, and Shanghai, China, 2009-2019.

Background: A viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There is limited understanding of virus-virus interactions due to lack of long-term population-level data. Methods: Our study leverages passive surveillance data of 10 human acute respiratory viruses from Beijing, Chongqing, Guangzhou, and Shanghai collected during 2009 to 2019: influenza A and B viruses; respiratory syncytial virus A and B; human parainfluenza virus (HPIV), adenovirus, metapneumovirus (HMPV), coronavirus, bocavirus (HBoV), and rhinovirus (HRV). We used a multivariate Bayesian hierarchical model to evaluate correlations in monthly prevalence of test-positive samples between virus pairs, adjusting for potential confounders. Results: Of 101,643 lab-tested patients, 33,650 tested positive for any acute respiratory virus, and 4,113 were co-infected with multiple viruses. After adjusting for intrinsic seasonality, long-term trends and multiple comparisons, Bayesian multivariate modeling found positive correlations for HPIV/HRV in all cities and for HBoV/HRV and HBoV/HMPV in three cities. Models restricted to children further revealed statistically significant associations for another ten pairs in three of the four cities. In contrast, no consistent correlation across cities was found among adults. Most virus-virus interactions exhibited substantial spatial heterogeneity. Conclusions: There was strong evidence for interactions among common respiratory viruses in highly populated urban settings. Consistent positive interactions across multiple cities were observed in viruses known to typically infect children. Future intervention programs such as development of combination vaccines may consider spatially consistent virus-virus interactions for more effective control.

[Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma].

OBJECTIVE: To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM). METHODS: The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens. RESULTS: The 41 patients underwent 97 mobilization collections, and the median number of CD34+ cells collected was 6.09 (0-34.07)×106/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34+ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34+ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34+ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05). CONCLUSION: PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34+ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.