Effectiveness of mobile smoking cessation treatment with 1-week nicotine replacement therapy sampling at outdoor smoking hotspots: A cluster randomized controlled trial.

AIMS: To evaluate the effectiveness of mobile smoking cessation (SC) treatment with 1-week nicotine replacement therapy (NRT) sampling on recruitment and quitting outcomes. DESIGN: Two-arm cluster RCT (1:1 ratio), single-blinded, at 244 recruitment sessions in Hong Kong outdoor smoking hotspots from October 2018-December 2019. SETTING: Participant were recruited by ambassadors and treated at the mobile SC truck. PARTICIPANTS: 834 adult (≥18 years, male 81.3%) daily smokers, Chinese-speaking, non-NRT users in the past month, consented after nurse-led intervention in mobile SC truck were randomized to the experimental (n = 482 male 79.5%) and the control group (n = 352, male 83.8%). INTERVENTION AND COMPARATOR: The experimental group received a 1-week free NRT sample, an NRT instruction card, and mobile SC treatment including onsite nurse-led brief medication advice (about 15 minutes) and referral to SC clinics. The control group received the same mobile SC treatment. MEASUREMENTS: Primary outcome was self-reported quit attempts at 1-month follow-up. Secondary outcomes included SC service use at 1 month, and biochemically validated abstinence (exhaled carbon monoxide < 4 ppm; or saliva cotinine < 10 ng/ml) at 6-month follow-up. Additionally, a post-hoc cost analysis was conducted. FINDINGS: By intention-to-treat, the two groups showed similar prevalence of quit attempts (44·4% versus 43·5%, risk ratio (RR) = 1·04, 95% confidence interval (CI) = 0·79-1·37, P = 0·79). Compared with the control group, the experimental group showed lower SC service use at clinics (32·4% versus 44·9%, RR = 0·72, 95%CI = 0·57-0·91, P = 0·006), but no significant difference in validated abstinence (4·6% versus 2·8%, RR = 1·64, 95%CI = 0·76-3·50, P = 0·21). The experimental recruitment sessions recruited more smokers for onsite medication advice than the control session (mean 6·7 vs 5·0, adjusted incident rate ratio = 1·30, 95%CI = 1·08-1·56, P = 0·005). CONCLUSIONS: Mobile smoking cessation treatment with 1-week nicotine replacement therapy sampling did not increase quit attempts or abstinence outcomes among recruited daily smokers in Hong Kong. The intervention increased smokers' uptake of onsite medication advice but reduced subsequent smoking cessation service use at clinics.

PD-1 blockade combined with chemotherapy and bevacizumab in DNA mismatch repair-proficient/microsatellite stable colorectal liver metastases.

Background: Single-agent immunotherapy is less effective in patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC). Whether pMMR/MSS mCRC patients benefit from combination immunotherapy remains unclear. This study aimed to evaluate the efficacy and safety of anti-programmed cell death protein 1 (PD-1) therapy combined with chemotherapy and bevacizumab in pMMR/MSS colorectal liver metastases (CRLM) patients. Methods: A total of 12 patients with pMMR/MSS CRLM treated at The Sixth Affiliated Hospital of Sun Yat-sen University were enrolled. All patients were treated with at least 4 doses of PD-1 monoclonal antibody combined with chemotherapy and bevacizumab as neoadjuvant/adjuvant therapy. Results: A total of 10 of the 12 patients received the combined therapies before primary tumor resection; the disease control rate (DCR) was 100% (10/10), and the objective response rate (ORR) was 70% (7/10). The ORR of liver metastases was 75% (9/12). Pathological complete response (pCR) was achieved in 1 primary tumor patient and 2 patients with hepatic lesions. A total of 5 patients underwent simultaneous resection of the primary tumor and liver metastases; 9 patients underwent microwave ablation for liver metastases. A total of 7 patients were assessed as having no evidence of disease (NED) with a median progression-free survival (PFS) interval of 9.2 (1.5-15.8) months after multimodality treatments for both primary and metastatic lesions. No severe immune-related adverse events (irAEs) and operational complications were observed. Conclusions: PD-1 blockade combined with chemotherapy and bevacizumab might be safe and effective for patients with pMMR/MSS CRLM. This treatment strategy might lead to better tumor regression and a higher chance of achieving NED.

Soil organic carbon fractions and their stability under different land uses in wind erosion area of Northeast China.

Exploring the physical fractions of organic carbon and influencing mechanisms in grassland, forest, and farmland soils in wind erosion area can provide scientific basis for carbon sequestration, land utilization, wind prevention measure making, and fertility restoration of sloping farmland in the region. We examined the differentiation of aggregate organic carbon and density fractionation organic carbon in 0-15 cm soil layer across grassland, forest, and sloping farmland with 350 m long and 5° slope gradient in the wind erosion area of Meilisi District, Qiqihar, Heilongjiang, as well as the sloping farmland in the downhill section, middle section, and uphill section with every 100 m apart from the bottom to the top. The results showed that soil aggregates >2 mm were all destroyed across grassland, forest, and farmland soils, while the percentage of aggregates <0.053 mm was significantly higher than that of other sizes. The percentage of various soil aggregates, organic carbon content from density fractionations, and the proportion of organic carbon in the heavy fraction aggregates in farmland were significantly lower than that in grassland and forest soils. Soil aggregates in the uphill section of farmland were completely destroyed, and organic carbon content in various size aggregates and density fractionations gradually decreased with increasing slope. The proportion of organic carbon in the heavy fraction aggregates decreased, but that in light fraction aggregates increased gradually. Soil organic carbon and available potassium were key factors affecting aggregate stability, aggregate organic carbon content, and organic carbon content in density fractionations, while the loss of organic carbon in aggregate led to a decrease in aggregate stability. In summary, compared with grassland and forest soils, the stability of soil aggregates, the aggregate organic carbon content, the organic carbon content in density fractionations, and the proportion of organic carbon in heavy fraction aggregates in farmland all decreased in the wind erosion area of Northeast China. With the increases of slope, the aggregate organic carbon content, the organic carbon content in density fractionations, and the proportion of organic carbon in the heavy fraction aggregates in sloping farmland all decreased. Planting trees, conserving and expanding grassland area, and increasing the application of organic materials in sloping farmland in wind erosion area are effective approaches to stabilize and increase carbon storage, improve soil structure, and enhance soil quality.

Farmed fur animals harbour viruses with zoonotic spillover potential.

Animals such as raccoon dogs, mink and muskrats are farmed for fur and are sometimes used as food or medicinal products1,2, yet they are also potential reservoirs of emerging pathogens3. Here we performed single-sample metatranscriptomic sequencing of internal tissues from 461 individual fur animals that were found dead due to disease. We characterized 125 virus species, including 36 that were novel and 39 at potentially high risk of cross-species transmission, including zoonotic spillover. Notably, we identified seven species of coronaviruses, expanding their known host range, and documented the cross-species transmission of a novel canine respiratory coronavirus to raccoon dogs and of bat HKU5-like coronaviruses to mink, present at a high abundance in lung tissues. Three subtypes of influenza A virus-H1N2, H5N6 and H6N2-were detected in the lungs of guinea pig, mink and muskrat, respectively. Multiple known zoonotic viruses, such as Japanese encephalitis virus and mammalian orthoreovirus4,5, were detected in guinea pigs. Raccoon dogs and mink carried the highest number of potentially high-risk viruses, while viruses from the Coronaviridae, Paramyxoviridae and Sedoreoviridae families commonly infected multiple hosts. These data also reveal potential virus transmission between farmed animals and wild animals, and from humans to farmed animals, indicating that fur farming represents an important transmission hub for viral zoonoses.

Deterministic Localization for Fully Automatic Operation: A Survey and Experiments.

With the rapid development of fully automatic operation (FAO) and location-based services, the evaluation criteria of average localization accuracy can no longer meet our demands, in favor of deterministic localization. However, most localization researches modeled localization performance function and enhanced it by minimizing average localization root mean square error (RMSE). The performance degradation in a small region was not considered. In this paper, we present a survey of deterministic localization and analyze the relationship between accuracy and certainty. In this paper, two common solutions of localization enhancement are presented and their localization certainties are discussed. Furthermore, we carry out related localization enhancement experiments in rail transit line and analyze their improvement on deterministic localization. The experimental results show that the overall localization performance is improved, while the deterministic localization requires the stricter solution to promote.

Exposures to particulate matters and childhood sleep disorders-A large study in three provinces in China.

OBJECTIVES: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter <2.5 µm and <1 µm, respectively) with sleep disorders in children. METHODS: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012-2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM2.5 and PM1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments. RESULTS: Long-term PM2.5 and PM1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM2.5 and PM1 per 10 µg/m3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM1 were found than that of PM2.5 in southeast region. CONCLUSION: Long-term PM2.5 and PM1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region.

PD-1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer.

BACKGROUND: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. METHODS: In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. RESULTS: By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10-8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). CONCLUSIONS: Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.

Association of mental disorders with sepsis: a bidirectional Mendelian randomization study.

Background: Substantial research evidence supports the correlation between mental disorders and sepsis. Nevertheless, the causal connection between a particular psychological disorder and sepsis remains unclear. Methods: For investigating the causal relationships between mental disorders and sepsis, genetic variants correlated with mental disorders, including anorexia nervosa (AN), attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder (PTSD), schizophrenia (SCZ), and tourette syndrome (TS), were all extracted from the Psychiatric Genomics Consortium (PGC). The causal estimates and direction between these mental disorders and sepsis were evaluated employing a two-sample bidirectional MR strategy. The inverse variance weighted (IVW) method was the primary approach utilized. Various sensitivity analyses were performed to confirm the validity of the causal effect. Meta-analysis, multivariable MR, and mediation MR were conducted to ensure the credibility and depth of this research. Results: The presence of AN was in relation to a greater likelihood of sepsis (OR 1.08, 95% CI 1.02-1.14; p = 0.013). A meta-analysis including validation cohorts supported this observation (OR 1.06, 95% CI 1.02-1.09). None of the investigated mental disorders appeared to be impacted when sepsis was set as the exposure factor. Even after adjusting for confounding factors, AN remained statistically significant (OR 1.08, 95% CI 1.02-1.15; p = 0.013). Mediation analysis indicated N-formylmethionine levels (with a mediated proportion of 7.47%), cystatin D levels (2.97%), ketogluconate Metabolism (17.41%) and N10-formyl-tetrahydrofolate biosynthesis (20.06%) might serve as mediators in the pathogenesis of AN-sepsis. Conclusion: At the gene prediction level, two-sample bidirectional MR analysis revealed that mental disorder AN had a causal association with an increased likelihood of sepsis. In addition, N-formylmethionine levels, cystatin D levels, ketogluconate metabolism and N10-formyl-tetrahydrofolate biosynthesis may function as potential mediators in the pathophysiology of AN-sepsis. Our research may contribute to the investigation of novel therapeutic strategies for mental illness and sepsis.

Caspase-8 promotes NLRP3 inflammasome activation mediates eye development defects in zebrafish larvae exposed to perfulorooctane sulfonate (PFOS).

Epidemiological evidence showed that serum high perfluorooctane sulfonate (PFOS) levels are associated with multiple eye related diseases, but the potential underlying molecular mechanisms remain poorly understood. Zebrafish and photoreceptor cell (661w) models were used to investigate the molecular mechanism of PFOS induced eye development defects. Our results showed a novel molecular mechanism of PFOS-induced inflammation response-mediated photoreceptor cell death associated with eye development defects. Inhibition of Caspase-8 activation significantly decreased photoreceptor cell death in PFOS exposure. Mechanistically, Toll-like receptor 4 (TLR4) mediates activation of Caspase-8 promote activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome to elicit maturation of interleukin-1 beta (IL-1ß) via Caspase-1 activation, facilitating photoreceptor cell inflammation damage in PFOS exposure. In addition, we also made a novel finding that Caspase-3 activation was increased via Caspase-8 activation and directly intensified cell death. Our results show the important role of Caspase-8 activation in PFOS induced eye development defects and highlight Caspase-8 mediated activation of the NLRP3 inflammation triggers activation of Caspase-1 and promote the maturation of IL-1ß in retinal inflammatory injury.

Low remnant cholesterol and the subsequent risk of new-onset atrial fibrillation: A prospective cohort study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia with high morbidity and mortality implications. Several studies have described a paradoxical inverse relationship between serum cholesterol and the risk of AF, but it remains unknown whether remnant cholesterol (RC) is associated with AF incidence. OBJECTIVE: This study aims to prospectively investigate the association between RC and AF. METHODS: A total of 392,783 participants free of AF at baseline from the UK Biobank were included for the analysis. Cox proportional hazards model, subgroup analysis, and sensitivity analyses were used to evaluate the independent association between RC levels and the risk of new-onset AF. Furthermore, we performed a discordance analysis by using the median cutoff points of low-density lipoprotein cholesterol (LDL-C) and RC. RESULTS: After a median follow-up of 12.8 years (interquartile range 12.0-13.6 years), a total of 23,558 participants experienced incident AF. Compared with the highest RC level, the lower RC level was associated with an increased risk of AF incidence (quartile 1 vs quartile 4: hazard ratio 1.396; 95% confidence interval [CI] 1.343-1.452). The results remained robust across a series of sensitivity analyses. In the discordance analyses, a significantly higher risk of AF was observed in participants with discordant low RC/high LDL-C levels than in those with concordant high RC/LDL-C levels. In the low LDL-C group, RC reduction even contributed to an additional 15.8% increased rate of incident AF (low RC/low LDL-C: hazard ratio 1.303; 95% CI 1.260-1.348 vs high RC/low LDL-C: hazard ratio 1.125; 95% CI 1.079-1.172). CONCLUSION: Low RC levels were associated with an increased risk of incident AF independent of traditional cardiovascular risk factors.

Efficacy of simple and very brief handgrip and isometric exercises for reducing withdrawal symptoms in cigarette smokers: A pilot randomized controlled trial.

INTRODUCTION: Withdrawal symptoms lead to smoking relapse and reduce the intention to quit. The present pilot RCT examined the effect of simple and very brief handgrip and isometric exercises on reducing withdrawal symptoms, measured by the strength of tobacco craving, Questionnaire of Smoking Urges-Brief (QSU-B), Mood and Physical Symptoms Scale (MPSS), and Positive and Negative Affect Schedule (PANAS). METHODS: In this 2-arm, open-labeled pilot RCT, 30 current smokers who had abstained from tobacco for at least 9 hours were randomly assigned (allocation ratio 1:1) to either the intervention group that watched a 5-minute video and did 5-minute handgrip and isometric exercises (pulling and pushing) or control group that watched 10-minute healthy-diet videos. Measurements were taken before, immediately after, and 10 minutes post-intervention. Outcomes were self-reported strength of tobacco craving, QSU-B, MPSS, and PANAS scores. The effect size for group-by-time interaction was assessed using Cohen's f2 (small=0.02, medium=0.15, large=0.35). RESULTS: Group-by-time interactions showed that the intervention group showed larger reductions than the control group in the strength of tobacco craving (Cohen's f2=0.54, 95% CI: 0.52-0.57), QSU-B (Cohen's f2=0.77; 95% CI: 0.74-0.80), and MPSS (Cohen's f2=0.51; 95% CI: 0.46-0.56) over the three measurement points. CONCLUSIONS: This RCT showed that simple and brief handgrip and isometric exercises could immediately reduce withdrawal symptoms and up to 10 minutes. CLINICAL TRIAL REGISTRATION: in https://clinicaltrials.gov/. IDENTIFIER: NCT04059497.

Effectiveness of Very Brief Advice on Tobacco Cessation: A Systematic Review and Meta-Analysis.

BACKGROUND: Very brief advice (VBA; ≤ 3 min) on quitting is practical and scalable during brief medical interactions with patients who smoke. This study aims to synthesize the effectiveness of VBA for smoking cessation and summarize the implementation strategies. METHODS: We searched randomized controlled trials aiming at tobacco abstinence and comparing VBA versus no smoking advice or no contact from Medline, Embase, CINAHL, Cochrane Library, PsycInfo databases, six Chinese databases, two trial registries ClinicalTrials.gov and WHO-ICTRP from inception to September 30, 2023. Grading of Recommendations, Assessment, Development, and Evaluations framework was used to assess the certainty of the evidence of the meta-analytic findings. The outcomes were self-reported long-term tobacco abstinence at least 6 months after treatment initiation, earlier than 6 months after treatment initiation, and quit attempts. Effect sizes were computed as risk ratio (RR) with 95% CI using frequentist random-effect models. DATA SYNTHESIS: Thirteen randomized controlled trials from 15 articles (n = 26,437) were included. There was moderate-certainty evidence that VBA significantly increased self-reported tobacco abstinence at ≥ 6 months in the adjusted model (adjusted risk ratio ARR 1.17, 95% CI: 1.07-1.27) compared with controls. The sensitivity analysis showed similar results when abstinence was verified by biochemical validation (n = 6 studies, RR 1.53, 95% CI 0.98-2.40). There was high-certainty evidence that VBA significantly increased abstinence at < 6 months (ARR 1.22, 95% CI: 1.01-1.47). Evidence of effect on quit attempts (ARR 1.03, 95% CI 0.97-1.08) was of very low certainty. DISCUSSION: VBA delivered in a clinical setting is effective in increasing self-reported tobacco abstinence, which provides support for wider adoption in clinical practice.

Positive association between chlorinated paraffins and the risk of allergic diseases in children and adolescents.

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.

Serum brain-derived neurotrophic factor levels in type 2 diabetes mellitus patients and its association with cognitive impairment: A meta-analysis.

OBJECTIVE: To compare the serum levels of brain-derived neurotrophic factor (BDNF) in type 2 diabetes mellitus (T2DM) patients with healthy controls (HC) and evaluate the BDNF levels in T2DM patients with/without cognitive impairment. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for the published English literature on BDNF in T2DM patients from inception to December 2022. The BDNF data in the T2DM and HC groups were extracted, and the study quality was evaluated using the Agency for Healthcare Research and Quality. A meta-analysis of the pooled data was conducted using Review Manager 5.3 and Stata 12.0 software. RESULTS: A total of 18 English articles fulfilled with inclusion criteria. The standard mean difference of the serum BDNF level was significantly lower in T2DM than that in the HC group (SMD: -2.04, z = 11.19, P <0.001). Besides, T2DM cognitive impairment group had a slightly lower serum BDNF level compared to the non-cognitive impairment group (SMD: -2.59, z = 1.87, P = 0.06). CONCLUSION: BDNF might be involved in the neuropathophysiology of cerebral damage in T2DM, especially cognitive impairment in T2DM.

Plasma proteomic characterization of colorectal cancer patients with FOLFOX chemotherapy by integrated proteomics technology.

BACKGROUND: Colorectal Cancer (CRC) is a prevalent form of cancer, and the effectiveness of the main postoperative chemotherapy treatment, FOLFOX, varies among patients. In this study, we aimed to identify potential biomarkers for predicting the prognosis of CRC patients treated with FOLFOX through plasma proteomic characterization. METHODS: Using a fully integrated sample preparation technology SISPROT-based proteomics workflow, we achieved deep proteome coverage and trained a machine learning model from a discovery cohort of 90 CRC patients to differentiate FOLFOX-sensitive and FOLFOX-resistant patients. The model was then validated by targeted proteomics on an independent test cohort of 26 patients. RESULTS: We achieved deep proteome coverage of 831 protein groups in total and 536 protein groups in average for non-depleted plasma from CRC patients by using a Orbitrap Exploris 240 with moderate sensitivity. Our results revealed distinct molecular changes in FOLFOX-sensitive and FOLFOX-resistant patients. We confidently identified known prognostic biomarkers for colorectal cancer, such as S100A4, LGALS1, and FABP5. The classifier based on the biomarker panel demonstrated a promised AUC value of 0.908 with 93% accuracy. Additionally, we established a protein panel to predict FOLFOX effectiveness, and several proteins within the panel were validated using targeted proteomic methods. CONCLUSIONS: Our study sheds light on the pathways affected in CRC patients treated with FOLFOX chemotherapy and identifies potential biomarkers that could be valuable for prognosis prediction. Our findings showed the potential of mass spectrometry-based proteomics and machine learning as an unbiased and systematic approach for discovering biomarkers in CRC.

Moniezia benedeni infection increases IgE+ cells in sheep (Ovis aries) small intestine.

The concentration of immunoglobulin (Ig) E is the lowest among serum Igs, but it can induces type I hypersensitivity and plays an important role in anti-parasitic infection. The present study aimed to explore the residence characteristics of IgE+ cells in the sheep small intestine and the impact of Moniezia benedeni infection on them. The recombinant plasmids pET-28a-IgE were constructed and induced and expressed in Escherichia coli. BL21 (DE3). The rabbit anti-sheep IgE polyclonal antibody was prepared using the obtained recombinant protein as antigen. Finally, the levels of IgE+ cells in the small intestine of healthy (Control group) and naturally M. benedeni-infected (Infected group) sheep were detected analyzed. The results showed that the rabbit anti-sheep IgE polyclonal antibody with good immunogenicity (titer = 1: 128000) could specifically bind to the heavy chain of natural sheep IgE. In the Control group, the IgE+ cells were mainly distributed in lamina propria of the small intestine, and the densities were significantly decreased from duodenum to ileum (P<0.05), with respective values of (4.28 cells / 104 µm2, 1.80 cells / 104 µm2, and 1.44 cells / 104 µm2 in duodenum, jejunum, and ileum. In the Infected group, IgE+ cells density were 6.26 cells / 104 µm2, 3.01 cells / 104 µm2, and 2.09 cells / 104 µm2 in duodenum, jejunum and ileum respectively, which were significantly higher in all segments compared to the Control group (P<0.05), increasing by 46.26%, 67.22% and 45.14%, respectively. In addition, compared with the Control group, the IgE protein levels were significantly increased in all intestinal segments of the Infected group (P<0.01), however, there was no significant differences among the different intestinal segments within the same group (P>0.05). The results demonstrated that M. benedeni infection could significantly increase the content of IgE and the distribution density of its secreting cells in sheep small intestine. The intestinal mucosal immune system of sheep presented obvious specificity against M. benedeni infection. This lays a good foundation for further exploring molecular mechanisms of the intestinal mucosal immune system monitoring and responding to M. benedeni infection.

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

BACKGROUND: During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. METHODS: Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). RESULTS: 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. CONCLUSION: Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.