Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy.

OBJECTIVE: This study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. RESULTS: The CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ±â€¯328.1 ng/mL, in contrast to the CC phenotype at 334.0 ±â€¯161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625-900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy. CONCLUSION: The CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.

Policy Learning for Actively Labeled Sample Selection on Lumbar Semi-supervised Classification.

Large labeled data bring significant performance improvement, but acquiring labeled medical data is particularly challenging due to the laborious, time-consuming, and medically qualified annotation. Semi-supervised learning has been employed to leverage unlabeled data. However, the quality and quantity of annotated data have a great influence on the performance of the semi-supervised model. Selecting informative samples through active learning is crucial and could improve model performance. Therefore, we propose a unified semi-supervised active learning architecture (RL-based SSAL) that alternately trains a semi-supervised network and performs active sample selection. Semi-supervised model is first well trained for sample selection, and selected label-required samples are annotated and added to the previously labeled dataset for subsequent semi-supervised model training. To learn to select the most informative samples, we adopt a policy learning-based approach that treats sample selection as a decision-making process. A novel reward function based on the product of predictive confidence and uncertainty is designed, aiming to select samples with high confidence and uncertainty. Comparisons with a semi-supervised baseline on collected lumbar disc herniation dataset demonstrate the effectiveness of the proposed RL-based SSAL, achieving over 3% promotion across different amounts of labeled data. Comparisons with other active learning methods and ablation studies reveal the superiority of proposed policy learning based on active sample selection and reward function. Our model trained with only 200 labeled data achieves an accuracy of 89.32% which is comparable to the performance achieved with the entire labeled dataset, demonstrating its significant advantage.

[Evaluation of a modified maxillary protraction appliance for the treatment of patients with skeletal Class â ¢ malocclusion associated with crowding].

PURPOSE: To investigate the efficacy of a modified maxillary protraction appliance in patients of skeletal Class Ⅲ with crowding. METHODS: Forty patients with skeletal Class Ⅲ malocclusion were divided into two groups, with 20 patients in each group. The experimental group had molar in a neutral or distal relationship and applied a modified maxillary protraction appliance, while the control group had molar mesial relationship and applied a conventional maxillary protraction appliance. Lateral cephalometric radiographs were taken before and after treatment in both groups for comparison. SPSS 22.0 software package was used for data analysis. RESULTS: The angle measurements taken before and after treatment showed a significant increase in SNA, ANB, SN-MP and U4-SN(P＜0.01), while SNB decreased(P＜0.01) in both groups. SN-OL changes were statistically different before and after treatment in the experimental group(P＜0.05). The sagittal measurements before and after treatment in both groups showed significant alterations in all(P＜0.05) but the length of the maxillary arch in both groups. For vertical measurements, U1-PP, L1-MP, U4-SN, U6-SN, and ANS-ME all increased (P＜0.05), while the changes of U4-PP and U6-PP in the two groups before and after treatment were statistically different(P＜0.05). Compared with the control group, the experimental group had a significantly increased maxillary arch length, a more remote location at U6, and a less variable molar relationship after treatment(P＜0.01). The two groups showed a variable amount of cephalometric measurements before and after treatment: the experimental group had a significant increase in maxillary arch length, a more remote position at U6, and a smaller change in molar relationship compared to the control group(P＜0.01). CONCLUSIONS: The modified maxillary protraction appliance showed good results for maxillary protraction and pushing the molar distally in patients with skeletal Class Ⅲ with crowding at neutral or distal molar relationship.

Stereo-Active Lone Pairs Induced Second Harmonic Generation Responses and Electrocatalytic Activity in Hybrid Material.

The lone pair electrons in the electronic structure of molecules have been a prominent research focus in chemistry for more than a century. Stable s2lone pair electrons significantly influence material properties, including thermoelectric properties, nonlinear optical properties, ferroelectricity, and electro(photo)catalysis.While major advances have been achieved in understanding the influence of lone pair electrons on material characteristics, research on this effect in organic-inorganic hybrid materials is in its initial stage. In this work, we successfully obtained a novel organic-inorganic hybrid material incorporating Ge with 4s2 lone pair electrons, (MeHDabco)2[GeBr3]4-H2O (MeHDabco = N-methyl-1,4-diazabicyclo[2.2.2]octane) (1). Driven by the stereochemically active lone pair electrons on the Ge2+, 1 crystallizes in the noncentrosymmetric space group P21 at room temperature and exhibits good second harmonic generation (SHG) responses. Interestingly, 1 also shows electrocatalytic activity for the hydrogen evolution reaction due to the existence of lone pair electrons on Ge2+ cations. The electrochemical experiment combined with the DFT calculations revealed the lone pair electrons act as both an active site for proton adsorption and facilitate the ionization of water. This work not only emphasizes the important role of lone pair electrons in material properties and functions but also provides new insight for designing novel Ge-based hybrid materials.

Screening of environmental stimuli for the positive regulation of stomatal aperture in centipedegrass.

Grasslands, the largest carbon pool in China, possess enormous potential for carbon sequestration. Increasing the stomatal aperture to increase the CO2 absorption capacity is a potential method to improve plant photosynthetic efficiency and ultimately enhance the carbon sequestration capacity of grass plants. Research on stomatal aperture regulation has focused mostly on Arabidopsis or crops, while research on grass plants in these areas is scarce, which seriously restricts the implementation of this grassland carbon sequestration strategy. Here, a widely used ecological grass, centipedegrass, was used as the experimental material. First, a convenient method for observing the stomatal aperture was developed. The leaves were floated in a potassium ion-containing open solution (67 mM KCl, pH 6.0) with the adaxial surface rather than the abaxial surface in contact with the solution and were cultivated under light for 1.5 h. Then, nail polish was applied on the adaxial surface, and a large number of open stomata were imprinted. Second, with the help of this improved method, the concentration‒response characteristics of the stomatal aperture to eleven environmental stimuli were tested. The stomatal aperture is dependent on these environmental stimuli in a concentration-dependent manner. The addition of 100 µM brassinolide led to the maximal stomatal aperture. This study provided a technical basis for manipulating stomatal opening to increase the carbon sequestration capacity of centipedegrass.

Single-Molecule White Circularly Polarized Photoluminescence and Electroluminescence from Dual-Emission Enantiomers.

The strategy of integrating conformational isomerization donors and chiral acceptor in single molecule was proposed to construct white circularly polarized luminescence (WCPL) materials in this work. Consequently, a pair of dual-emission enantiomers, namely (R/S)-DO-PTZ, were designed and synthesized, which displayed white emission with blue and yellow dual-emission bands in solution and solid films at Commission Internationale de l'Eclairage (CIE) coordinates of (0.30, 0.33) and (0.33, 0.35), respectively. Meanwhile, (R/S)-DO-PTZ exhibited high PLQY of up to 67% in doped films and obvious mirror-image WCPL signals with |glum| value of 3.0 × 10-3. Moreover, white circularly polarized electroluminescence (WCPEL) based on organic light-emitting diodes (OLEDs) with (R/S)-DO-PTZ as emitters were also achieved with CIE coordinates of (0.32, 0.37) and EQEmax of 4.7%, representing the state-of-the-art level of white OLEDs based on single-molecule purely organic emitters. By optimizing the device structure, warm WCPEL devices were further obtained with |gEL| value of 2.8 × 10-3, CIE coordinates of (0.37, 0.48) and EQEmax of up to 15.6%. To our knowledge, this is the first report of CP-WOLEDs based on single-molecule purely organic emitters.

Ultra-high Q resonances based on zero group-velocity modes accompanied by bound states in the continuum in 2D photonic crystal slabs.

Optical resonators made of 2D photonic crystal (PhC) slabs provide efficient ways to manipulate light at the nanoscale through small group-velocity modes with low radiation losses. The resonant modes in periodic photonic lattices are predominantly limited by nonleaky guided modes at the boundary of the Brillouin zone below the light cone. Here, we propose a mechanism for ultra-high Q resonators based on the bound states in the continuum (BICs) above the light cone that have zero-group velocity (ZGV) at an arbitrary Bloch wavevector. By means of the mode expansion method, the construction and evolution of avoided crossings and Friedrich-Wintgen BICs are theoretically investigated at the same time. By tuning geometric parameters of the PhC slab, the coalescence of eigenfrequencies for a pair of BIC and ZGV modes is achieved, indicating that the waveguide modes are confined longitudinally by small group-velocity propagation and transversely by BICs. Using this mechanism, we engineer ultra-high Q nanoscale resonators that can significantly suppress the radiative losses, despite the operating frequencies above the light cone and the momenta at the generic k point. Our work suggests that the designed devices possess potential applications in low-threshold lasers and enhanced nonlinear effects.

Alteration of soil pH induced by submerging/drainage and application of peanut straw biochar and its impact on Cd(II) availability in an acidic soil to indica-japonica rice varieties.

The effects of soil pH variations induced by submergence/drainage and biochar application on soil cadmium (Cd) availability to different rice (Oryza sativa L.) varieties are not well understood. This study aims to investigate the possible reasons for available Cd(II) reduction in paddy soil as influenced by biochar and to determine Cd(II) absorption and translocation rates in different parts of various rice varieties. A pot experiment in a greenhouse using four japonica and four indica rice varieties was conducted in Cd(II) contaminated paddy soil with peanut straw biochar. The results indicated that the submerging led to an increase in soil pH due to the consumption of protons (H+) by the reduction reactions of iron/manganese (Fe/Mn) oxides and sulfate (SO42-) and thus the decrease in soil available Cd(II) contents. However, the drainage decreased soil pH due to the release of protons during the oxidation of Fe2+, Mn2+, and S2- and thus the increase in soil available Cd(II) contents. Application of the biochar increased soil pH during soil submerging and inhibited the decline in soil pH during soil drainage, and thus decreased soil available Cd(II) contents under both submerging and drainage conditions. The indica rice varieties absorbed more Cd(II) in their roots and accumulated higher amounts of Cd(II) in their shoots and grains than the japonica rice varieties. The Cd(II) sensitive varieties exhibited a greater absorption and translocation rate of Cd(II) compared to the tolerant varieties of both indica and japonica rice. Biochar inhibited the absorption and accumulation of Cd(II) in the rice varieties, which ultimately lowered the Cd(II) contents in rice grains below the national food safety limit (0.2 mg kg-1). Overall, planting japonica rice varieties in Cd(II) polluted paddy soils combined with the use of biochar can effectively reduce Cd(II) content in rice grains which protects human health against Cd(II) toxicity.

Effects of CYP3A5*3 genetic polymorphisms on the pharmacokinetics of perampanel in Chinese pediatric patients with epilepsy.

PURPOSE: This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. RESULTS: The plasma concentration showed a linear correlation with the daily dose taken ( r  = 0.17; P  < 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5 ±â€…297.1 vs. 633.8 ±â€…305.5 µg/ml; P  = 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2 ±â€…1.7 vs. 3.8 ±â€…2.0; P  = 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8 ±â€…293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1 ±â€…165.6 ng/ml and 260.0 ±â€…36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8 ±â€…285.6 vs. 433.0 ±â€…227.2 ng/ml; P  = 0.042). CONCLUSION: The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.

Effect of Chinese Medicine in Patients with COVID-19: A Multi-center Retrospective Cohort Study.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).

Microbiota-derived I3A protects the intestine against radiation injury by activating AhR/IL-10/Wnt signaling and enhancing the abundance of probiotics.

The intestine is prone to radiation damage in patients undergoing radiotherapy for pelvic tumors. However, there are currently no effective drugs available for the prevention or treatment of radiation-induced enteropathy (RIE). In this study, we aimed at investigating the impact of indole-3-carboxaldehyde (I3A) derived from the intestinal microbiota on RIE. Intestinal organoids were isolated and cultivated for screening radioprotective tryptophan metabolites. A RIE model was established using 13 Gy whole-abdominal irradiation in male C57BL/6J mice. After oral administration of I3A, its radioprotective ability was assessed through the observation of survival rates, clinical scores, and pathological analysis. Intestinal stem cell survival and changes in the intestinal barrier were observed through immunofluorescence and immunohistochemistry. Subsequently, the radioprotective mechanisms of I3A was investigated through 16S rRNA and transcriptome sequencing, respectively. Finally, human colon cancer cells and organoids were cultured to assess the influence of I3A on tumor radiotherapy. I3A exhibited the most potent radioprotective effect on intestinal organoids. Oral administration of I3A treatment significantly increased the survival rate in irradiated mice, improved clinical and histological scores, mitigated mucosal damage, enhanced the proliferation and differentiation of Lgr5+ intestinal stem cells, and maintained intestinal barrier integrity. Furthermore, I3A enhanced the abundance of probiotics, and activated the AhR/IL-10/Wnt signaling pathway to promote intestinal epithelial proliferation. As a crucial tryptophan metabolite, I3A promotes intestinal epithelial cell proliferation through the AhR/IL-10/Wnt signaling pathway and upregulates the abundance of probiotics to treat RIE. Microbiota-derived I3A demonstrates potential clinical application value for the treatment of RIE.

Fractional exhaled nitric oxide, a potential biomarker for evaluating glucocorticoids treatment and prognosis in allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced TH2 inflammatory response. Fractional exhaled nitric oxide (FeNO) measurement has been used as a valuable tool in predicting the development and management of asthma, another typical TH2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear. OBJECTIVE: To investigate the association between FeNO and the prognosis of patients with ABPA to provide a basis for the use of FeNO in evaluating the efficacy of glucocorticoids in ABPA treatment. METHODS: This study comprised 2 parts; 58 patients were enrolled in the retrospective study. Clinical indexes in patients with different prognoses were compared, and receiver operating characteristic curve analysis was used to determine the threshold value. The prospective observational study involved 61 patients who were regularly followed up at 4 to 6 weeks and 6 months since the initial treatment. Patients were grouped on the basis of baseline FeNO values; correlation analysis was performed in the clinical data. RESULTS: Different prognoses were observed between patients with high and low baseline FeNO values, with a threshold value of 57 parts per billion. The percentage of Aspergillus fumigatus-specific IgE, percentage of positive A fumigatus-specific IgG, and relapse/exacerbation rate differed significantly between the high and low FeNO groups. Patients with higher FeNO needed longer treatment duration and showed shorter interval between glucocorticoid withdrawal and the next relapse/exacerbation. CONCLUSION: Our findings indicate that the level of FeNO is associated with the prognosis of ABPA. It can serve as an independent and valuable biomarker for evaluating the effectiveness of glucocorticoid treatment.

Destroyed lung contributes to the recurrence of hemoptysis after bronchial artery embolization in patients with post-tuberculosis bronchiectasis.

BACKGROUND: Bronchiectasis has high rates of hemoptysis and recurrent hemoptysis, which is inconsistent among various etiologies. Idiopathic bronchiectasis and post-tuberculous bronchiectasis are two important etiologies in China, but the differences in clinical features and risk factors of recurrent hemoptysis have not been elucidated. METHODS: Patients hospitalized for idiopathic bronchiectasis or post-tuberculosis bronchiectasis were included. Patients were followed up for at least 24 months post-BAE. Demographic characteristics and clinical data were collected and analyzed between idiopathic bronchiectasis and post-tuberculosis bronchiectasis. Based on the outcomes of recurrent severe hemoptysis in patients with post-tuberculosis bronchiectasis, Cox regression models were used to identify risk factors for recurrence. RESULTS: Among 417 patients including 352 idiopathic bronchiectasis and 65 post-tuberculous bronchiectasis, 209 (50.1%) were females. Compared with the idiopathic group, the proportion of patients with female (54.5% vs. 26.2%, p < 0.001), with sputum (79.5% vs. 36.9%, p < 0.001), isolation of Pseudomonas aeruginosa (28.7% vs. 7.7%, p < 0.001), and the number of bronchiectatic lobes≥ 3(98.3% vs 50.8%, p < 0.001) were lower, and the proportion of destroyed lung (4.5% vs. 26.6%, p < 0.001) and recurrence of severe hemoptysis (22.4% vs. 41.5%, p = 0.001) were higher in the post-tuberculous group. Among patients with post-tuberculosis bronchiectasis, destroyed lung [HR: 3.2(1.1,9.1), p = 0.026] and abnormal esophageal proper artery [HR: 2.8(1.1,7.0), p = 0.032] were two independent risk factors for the recurrence of hemoptysis. CONCLUSIONS: The recurrence rate of severe hemoptysis in patients with post-tuberculous bronchiectasis receiving BAE is high, and the proper esophageal artery should be actively evaluated and standardized treatment should be given.

Influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

PURPOSE: We aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a prospective cohort design study. High-performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentration. First-generation sequencing was performed to detect gene polymorphisms. Indicators of liver function were detected at least once before and after voriconazole therapy. RESULTS: Forty-one patients were included in this study, among which, 15 patients (36.6%) had voriconazole-induced liver injury. The proportion of voriconazole trough concentration > 5.5 µg·mL-1 patients within the DILI group (40.0%) was significantly higher compared to the control group (15.4%) (p < 0.05). After administration of voriconazole, the values of ALT (103.3 ± 80.3 U/L) and AST (79.9 ± 60.6 U/L) in the DILI group were higher than that in the control group (24.3 ± 24.8 and 30.4 ± 8.6 U/L) (p < 0.05). There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2, CYP2C19*3, CYP2C19*17, and UGT1A4 (rs2011425) (p > 0.05). CONCLUSION: There was a significant correlation between voriconazole-induced liver injury and voriconazole trough concentration in high-risk Uygur pediatric patients with allogeneic HSCT.

Intranasal Administration of Apelin-13 Ameliorates Cognitive Deficit in Streptozotocin-Induced Alzheimer's Disease Model via Enhancement of Nrf2-HO1 Pathways.

BACKGROUND: The discovery of novel diagnostic methods and therapies for Alzheimer's disease (AD) faces significant challenges. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate Apelin-13's mechanism of action in an in vivo model of AD induced by streptozocin (STZ). METHODS: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests, primarily, behavioral assessment, histological analysis, and biochemical assays, in order to evaluate synaptic plasticity and oxidative stress signaling pathways. RESULTS: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated by the enhancement of synaptic plasticity and the attenuation of oxidative stress signaling pathways. CONCLUSIONS: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

Genetic Evidence for a Causal Relationship Between Innate Leukocytes and the Risk of Digestive System Cancers in East Asians and Europeans.

Background: Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans. Methods: Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately. Results: Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007). Conclusions: Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.

A cost-effectiveness analysis of fluoride varnish application in preventing Root caries in elderly persons: a Markov simulation study.

BACKGROUND: Root caries are prevalent issues that affect dental health, particularly among elderly individuals with exposed root surfaces. Fluoride therapy has shown effectiveness in preventing root caries, but limited studies have addressed its cost-effectiveness in elderly persons population. This study aimed to evaluate the cost-effectiveness of a fluoride treatment program for preventing root caries in elderly persons within the context of Chinese public healthcare. METHODS: A Markov simulation model was adopted for the cost-effectiveness analysis in a hypothetical scenario from a healthcare system perspective. A 60-year-old subject with 23 teeth was simulated for 20 years. A 5% sodium fluoride varnish treatment was compared with no preventive intervention in terms of effectiveness and cost. Tooth years free of root caries were set as the effect. Transition probabilities were estimated from the data of a community-based cohort and published studies, and costs were based on documents published by the government. The incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Univariate and probabilistic sensitivity analyses were performed to evaluate the influence of data uncertainty. RESULTS: Fluoride treatment was more effective (with a difference of 10.20 root caries-free tooth years) but also more costly (with a difference of ¥1636.22). The ICER was ¥160.35 per root caries-free tooth year gained. One-way sensitivity analysis showed that the risk ratio of root caries in the fluoride treatment group influenced the result most. In the probabilistic sensitivity analysis, fluoride treatment was cost-effective in 70.5% of the simulated cases. CONCLUSIONS: Regular 5% sodium fluoride varnish application was cost-effective for preventing root caries in the elderly persons in most scenarios with the consideration of data uncertainty, but to a limited extent. Improved public dental health awareness may reduce the incremental cost and make the intervention more cost-effective. Overall, the study shed light on the economic viability and impact of such preventive interventions, providing a scientific basis for dental care policies and healthcare resource allocation.

The role of volatile organic compounds for assessing characteristics and severity of non-cystic fibrosis bronchiectasis: an observational study.

Background: Hypoxic conditions and Pseudomonas aeruginosa (P. aeruginosa) infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and P. aeruginosa infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC). Methods: EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and P. aeruginosa isolation was analyzed, which may relate to the severity of bronchiectasis disease. Results: Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in P. aeruginosa (+) group compared to the P. aeruginosa (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with P. aeruginosa isolation. Conclusion: The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.

Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.