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Abstract Background The complete and accurate human reference genome is important for functional genomics researches. Therefore, the incomplete reference genome and individual specific sequences have significant effects on various studies. Results we used two RNA-Seq datasets from human brain tissues and 10 mixed cell lines to investigate the completeness of human reference genome. First, we demonstrated that in previously identified ~5 Mb Asian and ~5 Mb African novel sequences that are absent from the human reference genome of NCBI build 36, ~211 kb and ~201 kb of them could be transcribed, respectively. Our results suggest that many of those transcribed regions are not specific to Asian and African, but also present in Caucasian. Then, we found that the expressions of 104 RefSeq genes that are unalignable to NCBI build 37 in brain and cell lines are higher than 0.1 RPKM. 55 of them are conserved across human, chimpanzee and macaque, suggesting that there are still a significant number of functional human genes absent from the human reference genome. Moreover, we identified hundreds of novel transcript contigs that cannot be aligned to NCBI build 37, RefSeq genes and EST sequences. Some of those novel transcript contigs are also conserved among human, chimpanzee and macaque. By positioning those contigs onto the human genome, we identified several large deletions in the reference genome. Several conserved novel transcript contigs were further validated by RT-PCR. Conclusion Our findings demonstrate that a significant number of genes are still absent from the incomplete human reference genome, highlighting the importance of further refining the human reference genome and curating those missing genes. Our study also shows the importance of de novo transcriptome assembly. The comparative approach between reference genome and other related human genomes based on the transcriptome provides an alternative way to refine the human reference genome.

Abstract Background Making a definitive preoperative diagnosis of solitary pulmonary nodules (SPNs) found by CT has been a clinical challenge. We previously demonstrated that microRNAs (miRNAs) could be used as biomarkers for lung cancer diagnosis. Here we investigate whether plasma microRNAs are useful in identifying lung cancer among individuals with CT-detected SPNs. Methods By using quantitative reverse transcriptase PCR analysis, we first determine plasma expressions of five miRNAs in a training set of 32 patients with malignant SPNs, 33 subjects with benign SPNs, and 29 healthy smokers to define a panel of miRNAs that has high diagnostic efficiency for lung cancer. We then validate the miRNA panel in a testing set of 76 patients with malignant SPNs and 80 patients with benign SPNs. Results In the training set, miR-21 and miR-210 display higher plasma expression levels, whereas miR-486-5p has lower expression level in patients with malignant SPNs, as compared to subjects with benign SPNs and healthy controls (all P ≤ 0.001). A logistic regression model with the best prediction was built on the basis of miR-21, miR-210, and miR-486-5p. The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.86 in distinguishing lung tumors from benign SPNs with 75.00% sensitivity and 84.95% specificity. Validation of the miRNA panel in the testing set confirms their diagnostic value that yields significant improvement over any single one. Conclusions The plasma miRNAs provide potential circulating biomarkers for noninvasively diagnosing lung cancer among individuals with SPNs, and could be further evaluated in clinical trials.

Abstract Background The Multinational Brassica rapa Genome Sequencing Project (BrGSP) has developed valuable genomic resources, including BAC libraries, BAC-end sequences, genetic and physical maps, and seed BAC sequences for Brassica rapa. An integrated linkage map between the amphidiploid B. napus and diploid B. rapa will facilitate the rapid transfer of these valuable resources from B. rapa to B. napus (Oilseed rape, Canola). Results In this study, we identified over 23,000 simple sequence repeats (SSRs) from 536 sequenced BACs. 890 SSR markers (designated as BrGMS) were developed and used for the construction of an integrated linkage map for the A genome in B. rapa and B. napus. Two hundred and nineteen BrGMS markers were integrated to an existing B. napus linkage map (BnaNZDH). Among these mapped BrGMS markers, 168 were only distributed on the A genome linkage groups (LGs), 18 distrubuted both on the A and C genome LGs, and 33 only distributed on the C genome LGs. Most of the A genome LGs in B. napus were collinear with the homoeologous LGs in B. rapa, although minor inversions or rearrangements occurred on A2 and A9. The mapping of these BAC-specific SSR markers enabled assignment of 161 sequenced B. rapa BACs, as well as the associated BAC contigs to the A genome LGs of B. napus. Conclusion The genetic mapping of SSR markers derived from sequenced BACs in B. rapa enabled direct links to be established between the B. napus linkage map and a B. rapa physical map, and thus the assignment of B. rapa BACs and the associated BAC contigs to the B. napus linkage map. This integrated genetic linkage map will facilitate exploitation of the B. rapa annotated genomic resources for gene tagging and map-based cloning in B. napus, and for comparative analysis of the A genome within Brassica species.

Abstract Background Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC will improve its outcome. The current techniques for NSCLC early detection are either invasive or have low accuracy. Molecular analyses of clinical specimens present promising diagnostic approaches. Non-coding RNAs (ncRNAs) play an important role in tumorigenesis and could be developed as biomarkers for cancer. Here we aimed to develop small nucleolar RNAs (snoRNAs), a common class of ncRNAs, as biomarkers for NSCLC early detection. The study comprised three phases: (1) profiling snoRNA signatures in 22 NSCLC tissues and matched noncancerous lung tissues by GeneChip Array, (2) validating expressions of the signatures by RT-qPCR in the tissues, and (3) evaluating plasma expressions of the snoRNAs in 37 NSCLC patients, 26 patients with chronic obstructive pulmonary disease (COPD), and 22 healthy subjects. Results In the surgical tissues, six snoRNAs were identified, which were overexpressed in all tumour tissues compared with their normal counterparts. The overexpressions of the genes in tumors were confirmed by RT-qPCR. The snoRNAs were stably present and reliably detectable in plasma. Of the six genes, three (SNORD33, SNORD66 and SNORD76) displayed higher plasma expressions in NSCLC patients compared with the cancer-free individuals (All < 0.01). The use of the three genes produced 81.1% sensitivity and 95.8% specificity in distinguishing NSCLC patients from both normal and COPD subjects. The plasma snoRNA expressions were not associated with stages and histological types of NSCLC (All > 0.05). Conclusions The identified snoRNAs provide potential markers for NSCLC early detection.

Dioxins, emanating from the waste incineration, constitutes an organic pollutant that poses considerable risks to the human health and environment. In this study, the corn straw char (CSC) and oak char (OC) derived from the electric heating or microwave gasification, and the coconut-shell activated carbon (AC) are employed as absorbents for the adsorption of dibenzofuran (DBF, dioxins model compound). Characterization techniques, including BET, X-ray CT, SEM-EDS, FTIR, and XPS, are performed to identify the DBF adsorption mechanism on the biochar. The results show that the biochar prepared by the microwave gasification has a more well-developed pore structure than that of the electric heating gasification. The higher porosity (16.94 %) and lower mineral content (1.75 %) are responsible for the effective adsorption of DBF onto AC. The adsorption capacity of CSC is proportional to the modified concentration of KOH. It is mainly ascribed to the decrement of carboxyl and lactone groups and the enhancement of alkaline functional groups on the biochar surface, which augments the hydrophobicity and π–π electron donor–acceptor (EDA) interaction. Instead, DBF adsorption capacity on the biochar is adversely affected by the HNO 3 modification. For all biochar samples, the corresponding maximum adsorption ratios are AC (87.11 %) > KOH-modified CSC (77.14 %) > unmodified CSC (49.11 %) > unmodified OC (39.70 %) > HNO 3 -modified CSC (36.09 %). The adsorption mechanisms of DBF on the gasified biochar encompass the pore filling, hydrophobicity, and π–π EDA interaction. A desirable adsorption capacity of DBF on the biochar prepared by the microwave gasification is attainable through augmenting the specific surface area while diminishing the oxygen-containing groups of the surface simultaneously. [Display omitted] • Biochar derived from microwave gasification has a well-developed pore structure. • X-ray CT is employed to study DBF adsorption mechanism onto biochar. • Biochar modified by KOH achieves the highest removal ratio of 77.14 %. • Adsorption is governed by pore filling, hydrophobicity, and π–π EDA interaction. [ABSTRACT FROM AUTHOR]

• A real-time harmonics detection method based on input observer is proposed. • Solving the problem of harmonics detection error caused by frequency fluctuation. • This method shall not be affected by the circuit topology. In this paper, a real-time detection method based on input observer is introduced for harmonics extraction of the grid currents in the case of fundamental frequency fluctuation. The proposed method has the advantages of fast detection speed and high detection precision, and can deal with the sudden changes in grid currents amplitudes and fundamental frequency. It works as follows: first of all, a phase-locked loop is used to extract the phase of grid currents in real-time. Then a state space model is constructed with grid currents and the harmonic components as unknown state variables. Finally, with the detected real-time phase, a linear time-varying observer based on the state space model is designed to estimate the unknown state variables. Its stability is guaranteed by Lyapunov function and LaSalle's Invariance Principle. Thus the extraction of grid currents harmonics is realized. Both simulation and experimental results show that the harmonic components of grid currents can be quickly and accurately extracted by proposed method even if the grid currents are distorted. [ABSTRACT FROM AUTHOR]

Synotis solidaginea Hand.-Mazz. (SSD) is a commonly used Tibetan medicinal herb with a long history of therapeutic use and has good medicinal value and development and utilization prospects. This study aimed to establish and validate a comprehensive strategy integrating UHPLC-Q Exactive Orbitrap HRMS chemical profiling and UHPLC-DAD multi-components quantification for the holistic quality evaluation of SSD. Using UHPLC-Q Exactive Orbitrap HRMS, a total of 58 components in SSD including flavonoids, organic acids, terpenoids, coumarin, and alkaloids were identified or tentatively characterized by authentic reference standards and accurate masses and characteristic fragment ions. The proportion of flavonoids and organic acids were the most in SSD. Subsequently, 7 characteristic components in SSD were quantified by a newly established UHPLC-DAD method that was validated in terms of linearity and ranges, LOD and LOQ, precision, repeatability, stability, and accuracy. Finally, the method was successfully used for the quality evaluation of 8 batches of SSD collected from 5 production areas in China. ANOVA and post hoc Tukey test are used to evaluate the differences in component content in SSD from different production areas. There are significant differences in the content of SSD from different regions (P < 0.05), which may be related to the climate, altitude, and other natural environments of the regions. This work laid a valuable foundation for further development and comprehensive quality control of SSD. [Display omitted] • A holistic method for quality control of Synotis solidaginea (SSD) was proposed. • 58 components in SSD were identified or tentatively characterized. • A UHPLC-DAD method for the quantification was developed and validated. • Laid a foundation for further development and holistic quality control of SSD. [ABSTRACT FROM AUTHOR]

Schisandra chinensis , as a famous medicinal and food homologous plant, has a long history of medicinal and dietary therapy. It has the functions of nourishing the kidney, calming the heart, tranquilising the mind, tonifying Qi and producing fluid to relieve mental stress, based on the theory of traditional Chinese medicine. Accumulating evidence has shown that S. chinensis polysaccharides (SCPs) are one of the most important bioactive macromolecules and exhibit diverse biological activities in vitro and in vivo , including neuroprotective, hepatoprotective, immunomodulatory, antioxidant, hypoglycemic, cardioprotective, antitumour and anti-inflammatory activities, etc. This review aims to thoroughly review the recent advances in the extraction and purification methods, structural features, biological activities and structure-activity relationships, potential applications and quality assessment of SCPs, and further highlight the therapeutic potentials and health functions of SCPs in the fields of therapeutic agents and functional food development. Future insights and challenges of SCPs were also critically discussed. Overall, the present review provides a theoretical overview for the further development and utilization of S. chinensis polysaccharides in the health food and pharmaceutical fields. [Display omitted] [ABSTRACT FROM AUTHOR]

The cost-effective sol-gel process for the preparation of phosphoric acid (PA) doped P- PBI membranes using PPA as both condensation reagent and solvent could avoid the use of hazardous organic solvents. However, optimizing the trade-off effect between mechanical properties and proton conductivity of sol-gel membranes by increasing polymer content is ineffective due to the limited solubility of P- PBI in PPA. Herein, we successfully fabricated a series of sol-gel membranes with tunable properties using a highly soluble polybenzimidazole (N- PBI). In addition, the sol-gel (5 wt%) N- PBI membrane was further specially dried and post-doped with PA to obtain a re-doped sol-gel N- PBI membrane. Therefore, the properties of PA-doped N- PBI membranes fabricated using three different processes- conv , sol-gel , and re-doped sol-gel -were thoroughly characterized. The sol-gel N- PBI membranes demonstrated a dependence of mechanical properties and proton conductivity on polymer content, with a maximum tensile strength of 7.0 MPa at 7 wt% polymer content and a maximum proton conductivity of 205 mS/cm (200 °C) at 2 wt% polymer content. The ADL-controlled re-doped sol-gel N- PBI membrane achieved higher saturated ADL than the sol-gel N- PBI membrane, resulting in higher proton conductivity and fuel cell performance. The sol-gel (2 wt%) N- PBI membrane exhibited an ultra-high H 2 /O 2 peak power density of 1058 mW/cm2 under an optimized operating condition, and the sol-gel (7 wt%) N- PBI membrane achieved stable operation without apparent degradation for over 2000 h at 160 °C with 0.3 A/cm2 current density. [Display omitted] • A highly soluble N- PBI was used as a precursor for the fabrication of sol-gel membranes. • A readily and cheap HT-PEM process has been developed. • The properties of the produced membranes were thoroughly evaluated systematically. [ABSTRACT FROM AUTHOR]

Highlights • 3D SPH-based internal-structure model of honeycomb sandwich panel is established. • Material parameters of the aramid honeycomb matrix are obtained. • Influences of particle size on the simulated results and computational efficiency are studied. • The whole deformation process of sandwich panels subjected to intense impulse is presented. • A comparison of the impact resistance of three different forms of panels is investigated. Abstract An experimental investigation on the dynamic response of composite sandwich panels, comprising two titanium alloy plates and an aramid honeycomb core, subjected to intense impulse loading was carried out with the electric gun method. And brief results were presented within this paper. Based on the experiments, simulations were conducted with SPH-based internal structure model using the AUTODYN software. Here, the elasto-plastic constitutive was adopted to describe the mechanical behaviour of the core and corresponding matrix constitutive parameters were obtained quantitatively. An optimal particle size was determined by comparing the effects of different particle sizes on computational efficiency and accuracy. Afterwards, the proposed SPH model was validated with the experiments, making it feasible for following studies. To study the weakening effect of the core, a stress decay coefficient was proposed, and the results proved that the aramid honeycomb core played an important role in weakening the reflected tensile wave. Finally, the impact resistance assessment, in which three different forms of panels were compared, indicated that the aramid honeycomb sandwich panel was superior to the other two. [ABSTRACT FROM AUTHOR]

Pancreatic stellate cells (PSCs) are crucial for metabolism and disease progression in pancreatic ductal adenocarcinoma (PDAC). However, detailed mechanisms of PSCs in glutamine (Gln) metabolism and tumor-stromal metabolic interactions have not been well clarified. Here we showed that tumor tissues displayed Gln deficiency in orthotopic PDAC models. Single-cell RNA sequencing analysis revealed metabolic heterogeneity in PDAC, with significantly higher expression of Gln catabolism pathway in stromal cells. Significantly higher glutamine synthetase (GS) protein expression was further validated in human tissues and cells. Elevated GS levels in tumor and stroma were independently prognostic of poorer prognosis in PDAC patients. Gln secreted by PSCs increased basal oxygen consumption rate in PCCs. Depletion of GS in PSCs significantly decreased PCCs proliferation in vitro and in vivo. Mechanistically, activation of Wnt signaling induced directly binding of β-catenin/TCF7 complex to GS promoter region and upregulated GS expression. Rescue experiments testified that GS overexpression recovered β-catenin knockdown-mediated function on Gln synthesis and tumor-promoting ability of PSCs. Overall, these findings identify the Wnt/β-catenin/TCF7/GS-mediated growth-promoting effect of PSCs and provide new insights into stromal Gln metabolism, which may offer novel therapeutic strategies for PDAC. • Metabolic heterogeneity generates Gln crosstalk between tumor and stroma in PDAC. • Gln synthesis is higher in PSCs compared to PCCs. • High GS expression in either tumor or stroma associates with poor prognosis in PDAC patients. • Targeting stromal GS induces tumor regression in vitro and in vivo. • The Wnt-β-catenin-TCF7-GS-Gln axis plays a key role in the growth-promoting effect of PSCs in PDAC. [ABSTRACT FROM AUTHOR]

This study aims to achieve an ultralow lasing threshold in CsPbBr 3 microplates (MPs), a crucial step toward developing electrically driven micro/nanolasers for optics integrated chips. We investigate the lasing behavior of CsPbBr 3 MPs under varying pressures by using static-state photoluminescence (PL), time-resolved PL (TRPL), and first-principles theory calculations based on density functional theory (DFT). Our results reveal that the lasing threshold initially decreases and then increases, with a critical turning point at 0.44 GPa. Notably, we achieve an optimal lasing threshold of 20.87 μJ/cm 2 after releasing pressure from 1.87 GPa, highlighting the potential of pressure modulation to optimize the lasing performance. At low pressure, pressure-induced phonon hardening enhances the barrier, preventing excitons decay from free states to trapping states. Conversely, at higher pressure, the increased density of surface defects, due to pressure-induced anisotropic contraction of lattice constants along the c -axis, leads to excitons decay from free states to trapping states. For CsPbBr 3 MPs, it is evident that only free excitons contribute to lasing, while both free and trapped excitons contribute to luminescence. These findings offer a novel strategy to optimize the lasing performance of perovskite micro/nanolasers, significantly advancing their potential for practical applications in optoelectronic devices.

A series of benzimidazoquinazolinone and dihydroquinazolinoquinazolinone derivatives were synthesized by deploying a method in which Mo(CO) 6 was used as both reductant and cyclization accelerator. The preliminary anti-cancer activities of the obtained products were measured and several compounds were revealed to exhibit anti-cancer activities.

Oxidative potential (OP) of particulate matter (PM) is an important indicator of its health effects. However, the relationship between OP and its key influencing factors remains unclear. In this study, size-segregated PM samples were collected in Qingdao, China, with major components and OP of PM thoroughly examined. The PM composition and sources contributing to OP were determined by hierarchical cluster analysis and positive matrix factorization model, and deposition of size-segregated and source-specific PM in respiratory tract and its resulting OP were assessed by multiple path particle dosimetry model. Dithiothreitol (DTT) activity decreased with increase of particle size in winter, while larger particles (4.2-10.2 μm) also contributed significantly to OP in summer. WSOC strongly correlated with OP in different particle sizes, while water-soluble iron, zinc, lead, and manganese had strong correlations with DTT activity for fine particles, reflecting the co-effects of particle composition and size on OP. Coarse and fine particles were more likely to be deposited in head and pulmonary region, respectively, with traffic and industrial sources contributing significantly to the deposited OP, especially in deeper regions of respiratory tract. This study highlights that the combined effects of different factors on PM OP need to be considered in health-oriented pollution abatement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To understand why Chlamydia trachomatis (Ct) (L2/434/Bu) favors hypoxia, we examined the dynamics of infected cells using a glycolysis-related PCR array and metabolomic analysis, along with the perturbation of nucleotide synthesis. Our findings revealed that, compared to normoxia, hypoxia with infection significantly and selectively upregulates the expression of genes related to glycolysis, glycogen degradation, and the pentose phosphate pathway. Furthermore, hypoxia induced a significant decrease in metabolite levels, particularly methionine-related metabolites, independent of infection, indicating efficient metabolism under hypoxia. Additionally, the perturbation of nucleotide synthesis with adenosine derivatives impaired Ct growth. Collectively, our results suggest that Ct favors a hypoxic environment with efficient metabolism, in which Ct readily activates glycolysis responsible for stable nucleotide synthesis as well as ATP supply., Competing Interests: Declaration of competing interest We have no conflicts of interest in association with the present study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Suicidal ideation (SI) assumes a pivotal role in predicting suicidal behaviors. The incidence of SI among high (junior and senior) school students is significantly higher than that of other age groups. The aim of this study is to explore the gender differences in SI among high school students in Yunnan Province., Method: A total of 6180 students in grades 7-12 in Yunnan province, China from May 2021 to May 2022 participated in this survey. Univariate analysis was employed to describe the influencing factors of male and female students' SI. Subsequently, data were stratified by gender. Adopting machine learning technique, including Least Absolute Shrinkage and Selection Operator (Lasso) and Boruta algorithm, and logistic regression model to estimate the direction and effect magnitude of the influencing factors., Results: The prevalence of SI was significantly higher for females (31.34 %) than males (16.73 %). The logistic regression model was established using the variables screened by Boruta algorithm, indicated that anxiety, depression, suffering emotion abuse or emotion neglect in childhood, non-suicidal self-injury, evening chronotype are common risk factors for SI in male and female students. Notably, female students who exhibited aggressive behavior, have experienced bullying, and were in the junior high school learning stage were more likely to report SI than their male counterparts., Conclusions: Females showed more vulnerability to SI than males especially among females in junior high school, reporting aggressive behavior and bullying experiences. Tailored prevention strategies, informed by these gender-related distinctions, should be developed and implemented., Competing Interests: Declaration of competing interest The authors have no conflicts to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Electron imaging of biological samples stained with heavy metals has enabled visualization of subcellular structures critical in chemical-, structural-, and neuro-biology. In particular, osmium tetroxide (OsO 4 ) has been widely adopted for selective lipid imaging. Despite the ubiquity of its use, the osmium speciation in lipid membranes and the process for contrast generation in electron microscopy (EM) have continued to be open questions, limiting efforts to improve staining protocols and therefore high-resolution nanoscale imaging of biological samples. Following our recent success using photoemission electron microscopy (PEEM) to image mouse brain tissues with synaptic resolution, we have used PEEM to determine the nanoscale electronic structure of Os-stained biological samples. Os(IV), in the form of OsO 2 , generates nanoaggregates in lipid membranes, leading to a strong spatial variation in the electronic structure and electron density of states. OsO 2 has a metallic electronic structure that drastically increases the electron density of states near the Fermi level. Depositing metallic OsO 2 in lipid membranes allows for strongly enhanced EM signals and conductivity of biological materials. The identification of the chemical species and understanding of the membrane contrast mechanism of Os-stained biological specimens provides a new opportunity for the development of staining protocols for high-resolution, high-contrast EM imaging., (© 2024 The Author(s). ChemBioChem published by Wiley-VCH GmbH.)

Background and Aims: Neurobiological models of addiction posit that addiction manifests through an amplified salience towards addiction-associated stimuli and a diminished responsiveness to non-addiction-related incentives. However, existing research on reward processing in individuals with problematic pornography use (PPU) has primarily been limited to sexual cue reactivity., Methods: In this event-related potential (ERP) study, we employed a risky decision-making task involving 30 individuals with PPU and 33 healthy controls (HCs) to examine the effects of PPU on non-pornographic (money) reward valuation., Results: Compared to HCs, individuals with PPU exhibited compromised sensitivity to monetary rewards. Specifically, while the HC group demonstrated a differential response in late positive potential (LPP) amplitude to various expected value (EV) levels, this pattern was absent in the PPU group. This impairment was associated with poorer adaptive decision-making, as evidenced by PPU participants' inability to adjust risk choices based on changes in EV, leading to a propensity for riskier decisions in disadvantageous situations., Discussion and Conclusions: The findings of impaired monetary evaluation in individuals with PPU may potentially explain why they continually pursue pornographic rewards while showing insensitivity to other rewards in daily life. Consequently, treatment development strategies may prioritize improving sensitivity to non-pornographic rewards within this population.

Introduction: Limb motor dysfunction is one of the challenges in rehabilitation after cerebral ischemic stroke (CIS) and greatly affects the quality of life of patients. This study aims to investigate the central mechanisms of the curative effect with multimodal magnetic resonance imaging (MRI), which will provide additional evidence to support the application of Xingnao Kaiqiao (XNKQ) acupuncture., Methods and Analysis: This trial is a randomized controlled trial. Patients who meet the criteria will be recruited and randomly divided into 2 groups. One group will receive acupuncture treatment and another group will not receive acupuncture treatment. Both groups will receive conventional treatment. In addition, 20 healthy individuals will be recruited who will not receive any treatment. The total course of treatment is 14 days. The primary outcome is multimodal MRI analysis. For safety assessment, adverse events will be observed and recorded., Ethics and Dissemination: The study involving human subjects was reviewed and approved by the Ethics Committee of IRB of The First Teaching Hospital of Tianjin University of TCM (TYLL2023[K]031). This study complied with the Declaration of Helsinki. Written informed consent about this study was provided by the participants. The results of this study will be published in a peer-reviewed journal., Clinical Trial Registration: Chinese Clinical Trial Registration Center (ChiCTR2300078315) https://www.chictr.org.cn/., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Xiao, Li, Chang, Lv, Li, Zhao and Dai.)

Detailing the physical basis of neural circuits with large-volume serial electron microscopy (EM), 'connectomics', has emerged as an invaluable tool in the neuroscience armamentarium. However, imaging synaptic resolution connectomes is currently limited to either transmission electron microscopy (TEM) or scanning electron microscopy (SEM). Here, we describe a third way, using photoemission electron microscopy (PEEM) which illuminates ultra-thin brain slices collected on solid substrates with UV light and images the photoelectron emission pattern with a wide-field electron microscope. PEEM works with existing sample preparations for EM and routinely provides sufficient resolution and contrast to reveal myelinated axons, somata, dendrites, and sub-cellular organelles. Under optimized conditions, PEEM provides synaptic resolution; and simulation and experiments show that PEEM can be transformatively fast, at Gigahertz pixel rates. We conclude that PEEM imaging leverages attractive aspects of SEM and TEM, namely reliable sample collection on robust substrates combined with fast wide-field imaging, and could enable faster data acquisition for next-generation circuit mapping.

Background: Despite the frequent comorbidity of affective and addictive disorders, the significance of affective dysregulation in problematic pornography use (PPU) is commonly disregarded. The objective of this study is to investigate whether individuals with PPU demonstrate increased sensitivity to negative emotional stimuli in comparison to healthy controls (HCs)., Methods: Electrophysiological responses were captured via event-related potentials (ERPs) from 27 individuals with PPU and 29 HCs. They completed an oddball task involving the presentation of deviant stimuli in the form of highly negative (HN), moderately negative (MN), and neutral images, with a standard stimulus being a neutral kettle image. To evaluate participants' subjective feelings of valence and arousal, the Self-Assessment Manikin (SAM) was employed., Results: Regarding subjective evaluations, individuals with PPU indicated diminished valence ratings for HN images as opposed to HCs. Concerning electrophysiological assessments, those with PPU manifested elevated N2 amplitudes in response to both HN and MN images when contrasted against neutral images. Additionally, PPU participants displayed an intensified P3 response to HN images in contrast to MN images, a distinction not evident within the HCs., Discussion: These outcomes suggest that individuals with PPU exhibited heightened reactivity toward negative stimuli. This increased sensitivity to negative cues could potentially play a role in the propensity of PPU individuals to resort to pornography as a coping mechanism for managing stress regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qu, Li and Wang.)

The leakage flow has a significant impact on the aerodynamic losses and efficiency of the compressor. This paper investigates the loss mechanism in the tip region based on a high-load cantilevered stator cascade. Firstly, a high-fidelity flow field structure was obtained based on the Enhanced Delay Detached Eddy Simulation (EDDES) method. Subsequently, the Liutex method was employed to study the vortex structures in the tip region. The results indicate the presence of a tip leakage vortex (TLV), passage vortex (PV), and induced vortex (IV) in the tip region. At i=4°,8°, the induced vortex interacts with the PV and low-energy fluid, forming a "three-shape" mixed vortex. Finally, a qualitative and quantitative analysis of the loss sources in the tip flow field was conducted based on the entropy generation rate, and the impact of the incidence on the losses was explored. The loss sources in the tip flow field included endwall loss, blade profile loss, wake loss, and secondary flow loss. At i=0°, the loss primarily originated from the endwall and blade profile, accounting for 40% and 39%, respectively. As the incidence increased, the absolute value of losses increased, and the proportion of loss caused by secondary flow significantly increased. At i=8°, the proportion of secondary flow loss reached 47%, indicating the most significant impact.

Fog significantly affects the air quality and human health. To investigate the health effects and mechanisms of atmospheric fine particulate matter (PM 2.5 ) during fog episodes, PM 2.5 samples were collected from the coastal suburb of Qingdao during different seasons from 2021 to 2022, with the major chemical composition in PM 2.5 analyzed. The oxidative potential (OP) of PM 2.5 was determined using the dithiothreitol (DTT) method. A positive matrix factorization model was adopted for PM 2.5 . Interpretable machine learning (IML) was used to reveal and quantify the key components and sources affecting OP. PM 2.5 exhibited higher oxidative toxicity during fog episodes. Water-soluble organic carbon (WSOC), NH 4 + , K + , and water-soluble Fe positively affected the enhancement of DTT V (volume-based DTT activity) during fog episodes. The IML analysis demonstrated that WSOC and K + contributed significantly to DTT V , with values of 0.31 ± 0.34 and 0.27 ± 0.22 nmol min -1 m -3 , respectively. Regarding the sources, coal combustion and biomass burning contributed significantly to DTT V (0.40 ± 0.38 and 0.39 ± 0.36 nmol min -1 m -3 , respectively), indicating the significant influence of combustion-related sources on OP. This study provides new insights into the effects of PM 2.5 compositions and sources on OP by applying IML models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Domain adaptation is a promising way to ease the costly data labeling process in the era of deep learning (DL). A practical situation is partial domain adaptation (PDA), where the label space of the target domain is a subset of that in the source domain. Although existing methods yield appealing performance in PDA tasks, it is highly presumable that computation overhead exists in deep PDA models since the target is only a subtask of the original problem. In this work, PDA and model compression are seamlessly integrated into a unified training process. The cross-domain distribution divergence is reduced by minimizing a soft-weighted maximum mean discrepancy (SWMMD), which is differentiable and functions as regularization during network training. We use gradient statistics to compress the overparameterized model to identify and prune redundant channels based on the corresponding scaling factors in batch normalization (BN) layers. The experimental results demonstrate that our method can achieve comparable classification performance to state-of-the-art methods on various PDA tasks, with a significant reduction in model size and computation overhead.

Galectin-3 (Gal-3) is a multifunctional protein that has been linked to fibrosis and inflammation in the cardiovascular system. In this study, we examined the impact of Gal-3 on inflammation and fibrosis in patients with arteriogenic erectile dysfunction (A-ED) and the underlying mechanisms involved. To induce arterial injury, we utilized cuffs on the periaqueductal common iliac arteries of Sprague‒Dawley (SD) rats and administered a high-fat diet to co-induce local atherosclerosis. Our results showed that we successfully developed a novel A-ED model that was validated based on histological evidence. In vivo, the vascular lumen of rats subjected to a high-fat diet and cuff placement exhibited significant narrowing, accompanied by the upregulation of Gal-3, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response protein 88 (MyD88) expression in the penile cavernosa. This led to the activation of nuclear factor kappa B 65 (NF-κB-p65), resulting in reduced intracavernosal pressure, endothelial nitric oxide synthase expression, and smooth muscle content, promoting inflammation and fibrosis. However, treatment with Gal-3 inhibitor-modified citrus pectin (MCP) significantly normalized those effects. In vitro, knocking down Gal-3 led to a significant reduction in TLR4, MyD88, and NF-κB-p65 expression in corpus cavernosum smooth muscle cells (CCSMCs), decreasing inflammation levels. In conclusion, inhibiting Gal-3 may improve A-ED by reducing inflammation, endothelial injury, and fibrosis in the penile corpus cavernosum through the TLR4/MyD88/NF-κB pathway. These findings highlight the potential therapeutic target of Gal-3 in A-ED., (© 2024. The Author(s).)

Zhenwu decoction (ZWD) is a famous classical formula in the treatment of heart failure (HF) with significant clinical effects. Owing to the complex material basis of ZWD, it is challenging to elucidate the pharmacodynamic substances and pharmacological mechanisms of ZWD against HF. Therefore, an ultrahigh-performance liquid chromatography system coupled with a high-resolution orbitrap mass spectrometry method was used to profile the chemical components and the absorbed prototype constituents in ISO-induced HF rat serum after oral administration of ZWD, and 33 out of 115 compounds were identified. In the in vivo study, ZWD could improve cardiac function and reduce the content of serum biochemical indexes, which are heart failure markers. With the help of network pharmacology and molecular docking simulation analysis, 112 ZWD targets oriented by HF were obtained, with STAT3, TNF, AKT1, VEGFA, and ALB as the core targets. Furthermore, we found that paeoniflorin and its derivatives may play a bigger role than other serum migrant components. Enriched pathway analysis yielded multiple HF-related signaling pathways, which indicated that ZWD may attenuate HF through the effect of PI3K-Akt, and MAPK pathways by regulating key targets such as STAT3, TNF, and AKT1. Finally, STAT3/MAPK pathways were experimentally validated in the anti-HF effect of ZWD. The phosphorylation levels of p38, JNK, ERK, and STAT3 were significantly increased in the ISO group and reversed by ZWD intervention. The results provided a reasonable strategy for the rapid screening of bioactive components in ZWD and a reference for quality control and further mechanism study of ZWD., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The problem of pesticide residue contamination has attracted widespread attention and poses a risk to human health. The current traditional pesticide residue detection methods have difficulty meeting rapid and diverse field screening requirements. Microfluidic technology integrates functions from sample preparation to detection, showing great potential for quick and accurate high-throughput detection of pesticide residues. This paper reviews the latest research progress on microfluidic technology for pesticide residue detection. First, the commonly used microfluidic materials are summarized, including silicon, glass, paper, polydimethylsiloxane, and polymethyl methacrylate. We evaluated their advantages and disadvantages in pesticide residue detection applications. Second, the current pesticide residue detection technology based on microfluidics and its application to real samples are summarized. Finally, we discuss this technology's present challenges and future research directions. This study is expected to provide a reference for the future development of microfluidic technology for pesticide residue detection., (© 2023 Wiley-VCH GmbH.)

Background and Objective: Vascular cognitive impairment with no dementia (VCIND) is considered to be the prodromal stage of vascular dementia, characterized by insidious onset. Although acupuncture and drug therapies are effective, the optimal therapy for VCIND remains to be further determined. Therefore, we conducted a network meta-analysis to compare the effectiveness of acupuncture therapies and current common medicines for VCIND., Methods: We searched eight electronic databases to identify eligible randomized controlled trials of patients with VCIND treated by acupuncture or drug therapies. The primary outcome was Montreal Cognitive Assessment, and the secondary outcome was Mini-Mental State Examination. We conducted the network meta-analysis within a Bayesian framework. Weighted mean difference with 95% confidence intervals were applied as effect sizes to continuous data for all outcomes. Sensitivity analysis was done to assess the robustness of the findings, and we also carried out a subgroup analysis based on age. We assessed the risk of bias using the Risk of Bias 2.0 tool and applied the Grade of Recommendation Assessment, Development and Evaluation (GRADE) to assess the quality of the outcomes. This study was registered with PROSPERO, number CRD42022331718., Results: A total of 33 studies with 14 interventions were included, including 2603 participants. In terms of the primary outcome, manual acupuncture plus herbal decoction was considered to be the most effective intervention ( P = 91.41%), followed by electroacupuncture ( P = 60.77%) and manual acupuncture plus piracetam ( P = 42.58%), whereas donepezil hydrochloride ranked the least efficacious intervention ( P = 54.19%). For the secondary outcome, electroacupuncture plus nimodipine was considered to be the most effective intervention ( P = 42.70%), followed by manual acupuncture plus nimodipine ( P = 30.62%) and manual acupuncture ( P = 28.89%), whereas nimodipine ranked the least efficacious intervention ( P = 44.56%)., Conclusion: Manual acupuncture plus herbal decoction might be the most effective intervention for VCIND. The combination of acupuncture and drug therapy had a tendency to perform better than monotherapy in terms of clinical outcomes., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=331718, identifier: CRD42022331718., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Xu, Zhong, Wang, Luo, Xiao, Dai, Han and Zhang.)

Background: Cuproptosis is recently emerging as a hot spot in cancer research. However, its role in pancreatic adenocarcinoma (PAAD) has not yet been clarified. This study aimed to explore the prognostic and therapeutic implications of cuproptosis-related genes in PAAD., Methods: Two hundred thirteen PAAD samples from the International Cancer Genome Consortium (ICGC) were split into training and validation sets in the ratio of 7:3. The Cox regression analyses generated a prognostic model using the ICGC cohort for training (n = 152) and validation (n = 61). The model was externally tested on the Gene Expression Omnibus (GEO) (n = 80) and The Cancer Genome Atlas (TCGA) datasets (n = 176). The clinical characteristics, molecular mechanisms, immune landscape, and treatment responses in model-defined subgroups were explored. The expression of an independent prognostic gene TSC22D2 was confirmed by public databases, real-time quantitative PCR (RT-qPCR), western blot (WB), and immunohistochemistry (IHC)., Results: A prognostic model was established based on three cuproptosis-related genes (TSC22D2, C6orf136, PRKDC). Patients were stratified into high- and low-risk groups using the risk score based on this model. PAAD patients in the high-risk group had a worse prognosis. The risk score was statistically significantly correlated with most clinicopathological characteristics. The risk score based on this model was an independent predictor of overall survival (OS) (HR = 10.7, p < 0.001), and was utilized to create a scoring nomogram with excellent prognostic value. High-risk patients had a higher TP53 mutation rate and a superior response to multiple targeted therapies and chemotherapeutic drugs, but might obtain fewer benefits from immunotherapy. Moreover, elevated TSC22D2 expression was discovered to be an independent prognostic predictor for OS (p < 0.001). Data from public databases and our own experiments showed that TSC22D2 expression was significantly higher in pancreatic cancer tissues/cells compared to normal tissues/cells., Conclusion: This novel model based on cuproptosis-related genes provided a robust biomarker for predicting the prognosis and treatment responses of PAAD. The potential roles and underlying mechanisms of TSC22D2 in PAAD need further explored., (© 2023. The Author(s).)

Background: Neuroendocrine carcinomas of the gastrointestinal tract (GI-NECs) remain a disease of grim prognosis with limited therapeutic options. Their molecular characteristics are still undefined. This study aimed to explore the underlying genetic basis and heterogeneity of GI-NECs., Methods: Comprehensive genomic analysis using whole-exome sequencing was performed on 143 formalin-fixed, paraffin-embedded samples of surgically resected GI-NEC with a thorough histological evaluation. Mutational signatures, somatic mutations, and copy number aberrations were analyzed and compared across anatomic locations and histological subtypes. Survival analysis was conducted to identify the independent factors., Results: In total, 143 GI-NECs were examined: the stomach, 87 cases (60.8%); the esophagus, 29 cases (20.3%); the colorectum, 20 cases (14.0%); and the small intestine, 7 cases (4.9%). Eighty-three (58.0%) and 60 (42.0%) cases were subclassified into small cell and large cell subtypes, respectively. GI-NECs showed distinct genetic alterations from their lung counterparts and non-neuroendocrine carcinomas in the same locations. Obvious heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across anatomic locations rather than histological subtypes. Except for tumor protein p53 (TP53) and retinoblastoma 1 (RB1), the most frequently mutated genes in the stomach, esophagus, colorectum, and small intestine were low-density lipoprotein receptor-related protein 1B (LRP1B), notch receptor 1 (NOTCH1), adenomatosis polyposis coli (APC), catenin beta 1 (CTNNB1), respectively. Mutations in the WNT-β-catenin, NOTCH and erythroblastic leukemia viral oncogene B (ERBB) pathways were prevalently identified in gastric, esophageal, and colorectal NECs, respectively. Importantly, 104 (72.7%) GI-NECs harbored putative clinically relevant alterations, and non-gastric location and RB1 bi-allelic inactivation with copy number alterations were identified as two independent poor prognostic factors. Furthermore, we found that tumor cells in GI-NECs first gain clonal mutations in TP53, RB1, NOTCH1 and APC, followed by subsequent whole-genome doubling (WGD) and post-WGD clonal mutations in LRP1B, CUB and Sushi multiple domains 3 (CSMD3), FAT tumor suppressor homolog 4 (FAT4) and erb-b2 receptor tyrosine kinase 4 (ERBB4), and finally develop subclonal mutations., Conclusions: GI-NECs harbor distinct genomic landscapes and demonstrate significant genetic heterogeneity across different anatomic locations. Moreover, potentially actionable alterations and prognostic factors were revealed for GI-NECs., (© 2022 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Background: This study aims to explore the relationship between the lymph nodes examined and survival benefits of postoperative radiotherapy in oral cavity squamous cell carcinoma patients with stage T1-2N1M0., Methods: This study retrieved patients who underwent dissection of the primary site and neck lymph nodes for pT1-2N1M0 oral cavity squamous cell carcinoma without adverse nodal features from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. Propensity score matching analysis was conducted, and the best cutoff value of the lymph nodes examined was determined by X-tile. Cancer-specific survival was the primary outcome. Univariable and multivariable analyses were performed to assess the relation between postoperative radiotherapy and cancer-specific survival, adjusting for other prognostic factors., Results: A total of 469 patients were finally enrolled according to our exclusion criteria, and then 119 pairs of patients were matched by propensity score matching analysis. The best cutoff value of the lymph nodes examined was determined by X-tile, stratifying patients into lymph nodes examined ≤16 group and lymph nodes examined >16 group. For the whole matched cohort, the choice of postoperative radiotherapy had no correlation with other factors (all p 's   > 0.05), and postoperative radiotherapy made no contribution to a better survival outcome for patients ( p  = 0.289). After stratified by the lymph nodes examined, in the lymph nodes examined ≤16 group, significantly improved CSS was found for those who undertook postoperative radiotherapy compared to those who just received surgery (unadjusted hazard ratio, 0.541; 95% confidence interval, 0.333-0.878; p  = 0.013)., Conclusions: Our study revealed that pT1-2N1M0 oral cavity squamous cell carcinoma patients were more likely to benefit from postoperative radiotherapy when unsatisfactory neck dissection was conducted, indicating that the number of lymph nodes examined might be a factor when clinicians do therapeutic planning for early-stage oral cavity squamous cell carcinoma patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Fan, Jiang, Fang, Li, Li, Chen and Zhang.)

Background: Colorectal carcinoma (CRC) harboring oncogenic fusions has been reported to be highly enriched in mismatch repair deficient (dMMR) tumors with MLH1 hypermethylation (MLH1 me+ ) and wild-type BRAF and RAS. In this study, dMMR CRCs were screened for oncogene fusions using sequential DNA and RNA next generation sequencing (NGS)., Results: Comprehensive analysis of fusion variants, genetic profiles and clinicopathological features in fusion-positive dMMR CRCs was performed. Among 193 consecutive dMMR CRCs, 39 cases were identified as MLH1 me+ BRAF/RAS wild-type. Eighteen fusion-positive cases were detected by DNA NGS, all of which were MLH1 me+ and BRAF/RAS wild-type. RNA NGS was sequentially conducted in the remaining 21 MLH1 me+ BRAF/RAS wild-type cases lacking oncogenic fusions by DNA NGS, and revealed four additional fusions, increasing the proportion of fusion-positive tumors from 46% (18/39) to 56% (22/39) in MLH1 me+ BRAF/RAS wild-type dMMR cases. All 22 fusions were found to involve RTK-RAS pathway. Most fusions affected targetable receptor tyrosine kinases, including NTRK1(9/22, 41%), NTRK3(5/22, 23%), ALK(3/22, 14%), RET(2/22, 9%) and MET(1/22, 5%), whilst only two fusions affected mitogen-activated protein kinase cascade components BRAF and MAPK1, respectively. RNF43 was identified as the most frequently mutated genes, followed by APC, TGFBR2, ATM, BRCA2 and FBXW7. The vast majority (19/22, 86%) displayed alterations in key WNT pathway components, whereas none harbored additional mutations in RTK-RAS pathway. In addition, fusion-positive tumors were typically diagnosed in elder patients and predominantly right-sided, and showed a significantly higher preponderance of hepatic flexure localization (P < 0.001) and poor differentiation (P = 0.019), compared to fusion-negative MLH1 me+ CRCs., Conclusions: We proved that sequential DNA and RNA NGS was highly effective for fusion detection in dMMR CRCs, and proposed an optimized practical fusion screening strategy. We further revealed that dMMR CRCs harboring oncogenic fusion was a genetically and clinicopathologically distinctive subgroup, and justified more precise molecular subtyping for personalized therapy., (© 2021. The Author(s).)

Background: Recently, many clinical experiments have evaluated the influences of liraglutide in the treatment of type 2 diabetes. However, the outcomes of these studies are inconsistent, and the number of high-quality prospective trials that conducted to assess the cardiovascular safety is limited. Hence, for this research, it was implemented for the assessment of the cardiovascular effectiveness and safety of liraglutide in type 2 diabetes patients., Methods: This research was a 26-week active controlled and randomized trial. Our research protocol follows the guidelines of Good Clinical Practice issued via the Helsinki Declaration and International Conference on Coordination. All the patients will receive the written informed consent in order to involve in our clinical experiment. The participants with type 2 diabetes aged from 18 years to 80 years, patients with 45.0 kg/m2 body-mass index or less, and with glycosylated hemoglobin of 7.5 to 10.0 percent, and received metformin (daily 1500 mg or more) for 3 months or longer were eligible. All the patients were randomized to 1 of 2 interventions (in the ratio of 1:1): liraglutide placebo once daily (blinded) and liraglutide once daily (blinded), respectively, both combined with the glimepiride and metformin (open-labeled). For the efficacy variable, the major endpoint was the baseline glycated hemoglobin change after treating for 26 weeks. The secondary end points involved: the percentage of participants who achieved the goals of postprandial blood glucose, fasting blood glucose, and glycosylated hemoglobin; the changes of mean postprandial blood glucose, fasting blood glucose, and the body weight, pancreatic B-cell function index, and changes in blood pressure and insulin resistance assessed by homeostasis model., Conclusions: For this research, the limitations involve the short trial period and the limitation of glimepiride in some countries, thus excluding the maximum doses of glimepiride., Trial Registration: This study protocol was registered in Research Registry (researchregistry6306)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study aimed to evaluate the efficacy and adherence of sublingual immunotherapy (SLIT) for house dust mite (HDM)-induced allergic rhinitis (AR) patients over 60 years old., Materials and Methods: Eighty-six AR patients aged 60-75 years old were randomly divided in the control and treatment group as 1:1 ratio. The control group was treated with standard pharmacotherapy while the treatment group was treated with SLIT plus pharmacotherapy on demand. Patients adherence, combined symptom and medication score (CSMS), visual analog scale (VAS), and presence of adverse events were evaluated in the baseline and after 6-months, 12-months and 24-months treatment., Results: Twenty-five (58.1%) subjects in the treatment group and 20 (46.5%) subjects in the control group completed the study (P > 0.05). The major reasons for premature cessation were out of touch and relieved symptoms. At the same time, CSMS and VAS of the patients over 60 years old in both groups significantly decreased from baseline to any post-baseline time point (all P < 0.05). The comparison of CSMS and VAS between the two groups revealed statistically significant differences in favor of the SLIT group at month 24 (P < 0.05), whereas no differences at month 6 and month 12 (all P > 0.05)., Conclusion: 41.9% of the patients dropped out within 2 years of SLIT treatment and the major reasons for premature cessation were out of touch and relieved symptoms. This study suggested that SLIT plus pharmacotherapy provided a greater clinical benefit than pharmacotherapy alone at two years., Competing Interests: Declaration of competing interest There are no financial or other issues that might lead to conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of the sublingual immunotherapy with dermatophagoides farinae drops on patients with allergic rhinitis., Method: One hundred and twelve cases were collected from adult patients with dust-mite allergic rhinitis of our hospital who could adhere to treatment and regular follow-up. These patients were randomly allocated to receive either sublingual immunotherapy (SLIT group, n = 56) or medical treatment (Control group, n = 56). To evaluate the clinical efficacy by side effects which were registered, symptom and medication scores which were assessed and rhinoconjunctivitis quality of life questionnaire (RQLQ) which was completed in the baseline and two years after treatment., Result: Dropouts after the 2 years' treatment were 5 of SLIT group and 4 of Control group respectively. SLIT group induced the significant reductions on both the symptom scores (7.81 ± 3.14 to 3.89 ± 2.01, P < 0.0 1) and the medication scores (2.86 ± 0.75 to 0.44 ± 0.06, P < 0.01). Meanwhile, Control group induced the reductions on both the symptom scores (8.01 ± 3.32 to 5.20 ± 2.43) and the medication scores (2.95 ± 0.80 to 1.75 ± 0.40). There were significant differences (P< 0. 01) in symptom and medication scores between the two groups after 2-year treatment. The patients in SLIT group had fewer symptoms and lower intake of medication. There were statistically significant differences in RQLQ between SLIT group [19 (15,22)] and Control group [36 (26,47)] after two years treatment (Z = -5. 21, P < 0.01). SLIT group also had significant improvement in RQLQ (Z = -6.10, P < 0.01) between before and after the treatment. There were 4 patients who showed adverse reactions in SLIT group (3 occurred in increment period, and 1 occurred in the maintenance period). The incidence of adverse reactions was 7.14%. No severe systemic side effects were registered., Conclusion: SLIT with standardized dermatophagoides farinae drops in China is safe and effective to patients with allergic rhinitis.