Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.

PURPOSE: As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis. METHODS: Gastric biopsies from different stomach microhabitats (n = 70) were subjected to 16S rRNA gene sequencing, and blood samples (n = 95) were subjected to untargeted metabolome (gas chromatography‒mass spectrometry, GC‒MS) analyses. The datasets were analysed using various bioinformatics approaches. RESULTS: The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer. CONCLUSION: The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.

Notopterygium Incisum Extract Promotes Apoptosis by Preventing the Degradation of BIM in Colorectal Cancer.

OBJECTIVE: Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism. METHODS: The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors. RESULTS: QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice. CONCLUSION: QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM.

Heterologous expression of the insect SVWC peptide WHIS1 inhibits Candida albicans invasion into A549 and HeLa epithelial cells.

Candida albicans (C. albicans), a microbe commonly isolated from Candida vaginitis patients with vaginal tract infections, transforms from yeast to hyphae and produces many toxins, adhesins, and invasins, as well as C. albicans biofilms resistant to antifungal antibiotic treatment. Effective agents against this pathogen are urgently needed. Antimicrobial peptides (AMPs) have been used to cure inflammation and infectious diseases. In this study, we isolated whole housefly larvae insect SVWC peptide 1 (WHIS1), a novel insect single von Willebrand factor C-domain protein (SVWC) peptide from whole housefly larvae. The expression pattern of WHIS1 showed a response to the stimulation of C. albicans. In contrast to other SVWC members, which function as antiviral peptides, interferon (IFN) analogs or pathogen recognition receptors (PRRs), which are the prokaryotically expressed MdWHIS1 protein, inhibit the growth of C. albicans. Eukaryotic heterologous expression of WHIS1 inhibited C. albicans invasion into A549 and HeLa cells. The heterologous expression of WHIS1 clearly inhibited hyphal formation both extracellularly and intracellularly. Furthermore, the mechanism of WHIS1 has demonstrated that it downregulates all key hyphal formation factors (ALS1, ALS3, ALS5, ECE1, HWP1, HGC1, EFG1, and ZAP1) both extracellularly and intracellularly. These data showed that heterologously expressed WHIS1 inhibits C. albicans invasion into epithelial cells by affecting hyphal formation and adhesion factor-related gene expression. These findings provide new potential drug candidates for treating C. albicans infection.

Risk of dyslipidemia and major adverse cardiac events with tofacitinib versus adalimumab in rheumatoid arthritis: a real-world cohort study from 7580 patients.

Objective: To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA). Methods: Data of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality. Results: A total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076-1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760-1.303]) and all-cause mortality (HR, 1.402 [0.887-2.215]). Conclusion: Tofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality.

Relay Annulation of Ammonium Ylides with Oxindole-Derived α,ß-Unsaturated Ketimines: Catalytic Construction of Spiro-polycyclic Oxindoles.

An ammonium ylide-based relay annulation was disclosed, which uses DABCO as the catalyst and oxindole-derived α,ß-unsaturated ketimines and γ-bromo-crotonates as the starting materials. This method enables the rapid assembly of a series of structurally novel spiro-polycyclic oxindoles containing a bicyclo[4.1.0]heptane moiety through simultaneous generation of three new bonds and two rings in one step under mild reaction conditions.

OsNLP3 enhances grain weight and reduces grain chalkiness in rice.

Grain weight, a key determinant of yield in rice (Oryza sativa L.), is governed primarily by genetic factors, whereas grain chalkiness, a detriment to grain quality, is intertwined with environmental factors such as mineral nutrients. Nitrogen (N) is recognized for its impact on grain chalkiness, yet the underlying molecular mechanisms remain elusive. This study revealed the pivotal role of rice NODULE INCEPTION-LIKE PROTEIN 3 (OsNLP3) in simultaneously regulating grain weight and grain chalkiness. Our investigation showed that the loss of OsNLP3 leads to a reduction in both grain weight and dimension, in contrast to the enhancement observed with OsNLP3 overexpression. OsNLP3 directly suppresses the expression of OsCEP6.1 and OsNF-YA8, which were identified as negative regulators associated with grain weight. Consequently, two novel regulatory modules, OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8, were identified as key players in grain weight regulation. Notably, the OsNLP3-OsNF-YA8 module not only augments grain weight but also mitigates grain chalkiness in response to N. This research clarifies the molecular mechanisms orchestrating grain weight through the OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8 modules, underscoring the pivotal role of the OsNLP3-OsNF-YA8 module in alleviating grain chalkiness. These findings offer potential targets for concurrently enhancing rice yield and quality.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Engineering properties optimization of dispersive soil by calcium silicate waste-The role of steel-making slag.

Steel slag (SS) is a byproduct that comes from the production of crude steel in alkaline oxidation furnaces. Resource utilization of steel slag, a calcium-silicon solid waste, is an urgent problem. This paper investigates a solid waste disposal method that applies different steel slag contents to modify dispersive soil. The engineering properties and modification mechanisms of dispersive soil specimens are studied and revealed by performing microstructure, mineral evolution, unconfined compressive strength (UCS), and tensile strength analysis. The pinhole test, mud ball crumb test (BCT), and mud cube crumb test (CCT) were carried out to determine the dispersivity of the soil specimens. Results show that when the steel slag content increases from 1% to 10%, the unconfined compressive strength and tensile strength increase by 176.05% and 75.40%, respectively. For soil specimens without curing time under 50 mm water head, the weight loss of the specimen with 10% steel slag content decreases by 72.03% compared to specimens with 1% steel slag content. Microstructural and mineralogical analyses indicate that the hydration reaction of steel slag changes the ionic composition of the soil and generates reaction products with effects such as filling and connection. To sum up, steel slag effectively improves water stability and mechanical properties of dispersive soil.

Clinical spectrum of late symptomatic neurosyphilis in China: an 11-year retrospective study.

OBJECTIVES: This study aimed to describe the clinical features of neurosyphilis in Chinese patients in an attempt to find clinical features that are helpful for the early identification of neurosyphilis. METHODS: This retrospective study included people with syphilis who visited Shanghai Skin Disease Hospital between January 2010 and December 2020. Lumbar puncture was performed on those who met the inclusion and exclusion criteria. The diagnosis of neurosyphilis was based on clinical and laboratory findings. The parameters were analysed statistically. RESULTS: Of the 3524 patients with neurosyphilis, 2111 (59.9%) and 1413 (40.1%) were asymptomatic and symptomatic neurosyphilis, respectively. General paresis was the most common type of symptomatic neurosyphilis (46.8%). The clinical manifestations of symptomatic neurosyphilis include psychiatric and neurotic symptoms, among which general paresis predominantly presented as psychiatric symptoms such as affective (66.7%) and memory disorder (72.9%). Tabes dorsalis is often presented as neurotic symptoms. One hundred fifty patients (10.6%) with symptomatic neurosyphilis presented candy signs, a rare and specific neurosyphilis symptom that is common in general paresis. Girdle sensation was presented in 13 patients, mainly with tabes dorsalis, which had not been reported in previous studies. CONCLUSIONS: Notably, the candy sign is identified as a specific symptom of general paresis, while girdle sensations are highlighted as a particular symptom of tabes dorsalis. This is the largest study describing the clinical spectrum of neurosyphilis since the onset of the penicillin era and could help doctors learn more about the disease. A comprehensive description of the possible clinical manifestations of late symptomatic neurosyphilis, particularly highlighting rare symptoms, can identify suspicious patients and prevent diagnostic delays.

Cartilage-Inspired, High-Strength, and Heat-Tolerant Lubricating Hydrogels by Macrophase Separation.

Hydrogels are considered as a potential cartilage replacement material based on their structure being similar to natural cartilage, which are of great significance in repairing cartilage defects. However, it is difficult for the existing hydrogels to combine the high load bearing and low friction properties (37 °C) of cartilage through sample methods. Herein, we report a facile and new fabrication strategy to construct the PNIPAm/EYL hydrogel by using the macrophase separation of supersaturated N-isopropylacrylamide (NIPAm) monomer solution to promote the formation of liposomes from egg yolk lecithin (EYL) and asymmetric template method. The PNIPAm/EYL hydrogels possess a relatively high compressive strength (more than 12 MPa), fracture energy (9820 J/m2), good fatigue resistance, lubricating properties, and excellent biocompatibility. Compared with the PNIPAm hydrogel, the friction coefficient (COF 0.046) of PNIPAm/EYL hydrogel is reduced by 50%. More importantly, the COF (0.056) of PNIPAm/EYL hydrogel above lower critical solution temperature (LCST) does not increase significantly, exhibiting heat-tolerant lubricity. The finite element analysis further proves that PNIPAm/EYL hydrogel can effectively disperse the applied stress and dissipate energy under load conditions. This work not only provides new insights for the design of high-strength lubricating hydrogels but also lays a foundation for the treatment of cartilage injury as a substitute material.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes.

SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.

Could ceftriaxone be a viable alternative to penicillin for the treatment of ocular syphilis?

This study was conducted to compare the effectiveness of ceftriaxone with that of aqueous crystalline penicillin G in treating ocular syphilis. We conducted a retrospective study from 2010 to 2021. Syphilis patients were administered either ceftriaxone (2 g intravenously daily for 14 days) or aqueous crystalline penicillin G [4 million units (MU) intravenously every 4 h for 14 days] as therapeutic interventions. Subsequently, we utilized these two groups to assess the serological results, cerebrospinal fluid analysis, and visual acuity at time intervals spanning 3 to 6 months post-treatment. A total of 205 patients were included, with 34 assigned to the ceftriaxone group and 171 to the penicillin group. The median age of patients was 56 years, with an interquartile range of 49-62 years, and 137 of them (66.8%) were male. Between 3 and 6 months after treatment, 13 patients (38.2%) in the ceftriaxone group and 82 patients (48.0%) in the penicillin group demonstrated effective treatment based on the clinical and laboratory parameters. The crude odds ratio (OR) was 0.672 (95% confidence interval [CI]: 0.316-1.428, P = 0.301), indicating no significant difference in effectiveness between the two groups. Thirty patients (17.5%) in the penicillin group and six patients (17.6%) in the ceftriaxone group did not experience successful outcomes. Notably, no serious adverse effects were reported in both the groups. There was no significant difference in the effectiveness of ceftriaxone and aqueous crystalline penicillin G in treating ocular syphilis. The administration of ceftriaxone without requiring hospitalization presents a convenient and safe alternative treatment option for ocular syphilis.

1,5-Hydrogen atom transfer of α-iminyl radical cations: a new platform for relay annulation for pyridine derivatives and axially chiral heterobiaryls.

The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,ß-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (ß-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.

Investigation of core symptoms and symptom clusters in maintenance hemodialysis patients: A network analysis.

PURPOSE: To construct a symptom network of maintenance hemodialysis patients and identify the core symptoms and core symptom clusters. Finally, this study provides a reference for accurate symptom management. DESIGN AND METHOD: A correlational cross-sectional design. A total of 368 patients who underwent maintenance hemodialysis were enrolled from two hemodialysis centers in Chengdu, Sichuan Province, China. A symptom network was constructed with the R coding language to analyze the centrality index. Symptom clusters were extracted by exploratory factor analysis, and core symptom clusters were preliminarily determined according to the centrality index of the symptom network. FINDINGS: The most common symptoms in maintenance hemodialysis patients were fatigue, dry skin, and pruritus. In the symptom network, headache had the highest mediation centrality (rB = 2.789) and closeness centrality (rC = 2.218) and the greatest intensity of numbness or tingling in the feet (rS = 1.952). A total of six symptom clusters were extracted, including pain and discomfort symptom clusters, emotional symptom clusters, gastrointestinal symptom clusters, sleep disorder symptom clusters, dry symptom clusters, and sexual dysfunction symptom clusters. The cumulative variance contribution rate was 69.269%. CONCLUSIONS: Fatigue, dry skin, and pruritus are the sentinel symptoms of maintenance hemodialysis patients, headache is the core symptom and bridge symptom, and pain symptom clusters are the core symptom clusters of MHD patients. Nurses can develop interventions based on core symptoms and symptom clusters to improve the effectiveness of symptom management in maintenance hemodialysis patients. CLINICAL RELEVANCE: Understanding the core symptoms and symptom groups that plague maintenance hemodialysis patients is critical to providing accurate symptom management. To ensure that maintenance hemodialysis patients receive effective support during treatment, reduce the adverse effects of symptoms, and improve the quality of life of patients.

Clinical-radiomics nomogram for the risk prediction of esophageal fistula in patients with esophageal squamous cell carcinoma treated with intensity-modulated radiation therapy or volumetric-modulated arc therapy.

Background: Esophageal fistula (EF) is a serious adverse event as a result of radiotherapy in patients with esophageal cancer (EC). We aimed to identify the predictive factors and establish a prediction model of EF in patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Methods: Patients with ESCC treated with IMRT or VMAT from January 2013 to December 2020 at Xijing Hospital were retrospectively analyzed. Ultimately, 43 patients with EF and 129 patients without EF were included in the analysis and propensity-score matched in a 1:3 ratio. The clinical characteristics and radiomics features were extracted. Univariate and multivariate stepwise logistic regression analyses were used to determine the risk factors associated with EF. Results: The median follow-up time was 24.0 months (range, 1.3-104.9 months), and the median overall survival (OS) was 13.1 months in patients with EF. A total of 1,158 radiomics features were extracted, and eight radiomics features were selected for inclusion into a model for predicting EF, with an area under the receiver operating characteristic curve (AUC) value of 0.794. Multivariate analysis showed that tumor length, tumor volume, T stage, lymphocyte rate (LR), and grade IV esophagus stenosis were related to EF, and the AUC value of clinical model for predicting EF was 0.849. The clinical-radiomics model had the best performance in predicting EF with an AUC value of 0.896. Conclusions: The clinical-radiomics nomogram can predict the risk of EF in ESCC patients and is helpful for the individualized treatment of EC.

Rapid Detection of Bacterial Pathogens Causing Lower Respiratory Tract Infections via Microfluidic-Chip-Based Loop-Mediated Isothermal Amplification.

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.

An observational prospective study based on a large cohort of HIV-negative neurosyphilis patients with particular reference to the Jarisch-Herxheimer reaction.

PURPOSE: The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients. METHODS: A prospective study cohort of 772 cases with almost all stages of neurosyphilis depicted the features of JHR including occurrence rate, risk profiles, clinical manifestations, medical management and prognosis. RESULTS: The total occurrence rate of JHR was 9.3% (95% CI, 7.3-11.4%), including 4.1% (95% CI, 2.7-5.6%) with severe JHR. The reaction started 5 h after treatment initiation, peaked after 8 h, and subsided after 18 h. Patients with severe JHR experienced a longer recovery time (26 h). Patients with general paresis (OR = 6.825), ocular syphilis (OR = 3.974), pleocytosis (OR = 2.426), or a high CSF-VDRL titre (per log2 titre increase, OR = 2.235) were more likely to experience JHR. Patients with general paresis had an 11.759-fold increased risk of severe JHR. Worsening symptoms included cognitive impairment, mania, nonsense speech, and dysphoria, while symptoms of hallucination, urination disorder, seizures, myoclonus, or aphasia appeared as new-onset symptoms. Neurosyphilis treatment did not need to be interrupted in most patients with JHR and could be reinstated in patients with seizures under supportive medication when JHR subsided. CONCLUSION: Severe JHR displayed a 4.1% occurrence rate and clinicians should pay particular attention to patients at a higher risk of JHR. The neurosyphilis treatment regime can be restarted under intensive observation for patients with severe JHR and, if necessary, supportive medication should be initiated and continued until the end of therapy.

Phthalate ester (PAEs) accumulation in wheat tissues and dynamic changes of rhizosphere microorganisms in the field with plastic-film residue.

Phthalates acid esters (PAEs) have accumulated in soil and crops like wheat as a result of the widespread usage of plastic films. It is yet unclear, nevertheless, how these dynamic variations in PAE accumulation in wheat tissues relate to rhizosphere bacteria in the field. In this work, a field root-bag experiment was conducted to examine the changes of PAEs accumulation in the rhizosphere soil and wheat tissues under film residue conditions at four different growth stages of wheat, and to clarify the roles played by the microbial community in the alterations. Results showed that the plastic film residues significantly increased the concentrations of PAEs in soils, wheat roots, straw and grains. The maximum ΣPAEs concentration in soils and different wheat tissues appeared at the maturity, with the ΣPAEs concentration of 1.57 mg kg-1, 4.77 mg kg-1, 5.21 mg kg-1, 1.81 mg kg-1 for rhizosphere soils, wheat roots, straw and grains, respectively. The plastic film residues significantly changed the functions and components of the bacterial community, increased the stochastic processes of the bacterial community assembly, and reduced the complexity and stability of the bacterial network. In addition, the present study identified some bacteria associated with plastic film residues and PAEs degradation in key-stone taxa, and their relative abundances were positive related to the ΣPAEs concentration in soils. The PAEs content and key-stone taxa in rhizosphere soil play a crucial role in the formation of rhizosphere soil bacterial communities. This field study provides valuable information for better understanding the role of microorganisms in the complex system consisting of film residue, soil and crops.

Impact of setup errors on the robustness of linac-based single-isocenter coplanar and non-coplanar VMAT plans for multiple brain metastases.

PURPOSE: Patient setup errors have been a primary concern impacting the dose delivery accuracy in radiation therapy. A robust treatment plan might mitigate the effects of patient setup errors. In this reported study, we aimed to evaluate the impact of translational and rotational errors on the robustness of linac-based, single-isocenter, coplanar, and non-coplanar volumetric modulated arc therapy treatment plans for multiple brain metastases. METHODS: Fifteen patients were retrospectively selected for this study with a combined total of 49 gross tumor volumes (GTVs). Single-isocenter coplanar and non-coplanar plans were generated first with a prescribed dose of 40 Gy in 5 fractions or 42 Gy in 7 fractions to cover 95% of planning target volume (PTV). Next, four setup errors (+1  and +2 mm translation, and +1° and +2° rotation) were applied individually to generate modified plans. Different plan quality evaluation metrics were compared between coplanar and non-coplanar plans. 3D gamma analysis (3%/2 mm) was performed to compare the modified plans (+2 mm and +2° only) and the original plans. Paired t-test was conducted for statistical analysis. RESULTS: After applying setup errors, variations of all plan evaluation metrics were similar (p > 0.05). The worst case for V100% to GTV was 92.07% ± 6.13% in the case of +2 mm translational error. 3D gamma pass rates were > 90% for both coplanar (+2 mm and +2°) and the +2 mm non-coplanar groups but was 87.40% ± 6.89% for the +2° non-coplanar group. CONCLUSION: Translational errors have a greater impact on PTV and GTV dose coverage for both planning methods. Rotational errors have a greater negative impact on gamma pass rates of non-coplanar plans. Plan evaluation metrics after applying setup errors showed that both coplanar and non-coplanar plans were robust and clinically acceptable.