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Objective: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is rare, and manifestations of autonomic dysregulation are diverse and may be overlooked. We aimed to evaluate the incidence of these manifestations. Methods: Patients with ROHHAD syndrome reported before and after 2019 were divided into groups 1 and 2. Patients who were diagnosed at three regional hospitals in China were included in group 3. We collected the age of each specific term of the ROHHAD (neurogenic tumor, NET) acronym and the detailed manifestations of each term, and compared them among the three groups. Results: A total of 16 patients were diagnosed within the 2-year period. Two had neurogenic tumors and cognitive and behavioral abnormalities before developing rapid obesity. At least 93.8% of the patients had ≥ 4 symptoms of autonomic dysregulation. When comparing autonomic dysregulation among groups 1–3, the rates of cardiovascular manifestations were NA vs 12.8% vs 81.2%; gastrointestinal disturbances were 11.4% vs 8.5% vs 62.5%; strabismus was 25.7% vs 12.8% vs 62.5%; sleep disturbance was NA vs 6.4% vs 50.0%; and abnormal pain threshold was NA vs 10.6% vs 25.0% (all P < 0.05). The rates of cognitive and behavioral abnormalities were NA vs 29.8% and 87.5% (P < 0.01). Conclusion: Rapid-onset obesity is not always the first sign of ROHHAD syndrome. Higher rates of autonomic dysregulation and cognitive and behavioral abnormalities with multiple manifestations of autonomic dysregulation coexisted in our cohort, indicating that evaluations of autonomic function and the limbic system should be strengthened when assessing this condition.

Abstract Non-small cell lung cancer (NSCLC) constitutes the majority of lung cancer cases, accounting for over 80%. RNAs in EVs play a pivotal role in various biological and pathological processes mediated by extracellular vesicle (EV). Long non-coding RNAs (lncRNAs) are widely associated with cancer-related functions, including cell proliferation, migration, invasion, and drug resistance. Tumor-associated macrophages are recognized as pivotal contributors to tumorigenesis. Given these insights, this study aims to uncover the impact of lncRNA NORAD in EVs derived from M2 macrophages in NSCLC cell lines and xenograft mouse models of NSCLC. EVs were meticulously isolated and verified based on their morphology and specific biomarkers. The interaction between lncRNA NORAD and SMIM22 was investigated using immunoprecipitation. The influence of SMIM22/GALE or lncRNA NORAD in EVs on glycolysis was assessed in NSCLC cell lines. Additionally, we evaluated the effects of M2 macrophage-derived lncRNA NORAD in EVs on cell proliferation and apoptosis through colony formation and flow cytometry assays. Furthermore, the impact of M2 macrophage-derived lncRNA NORAD in EVs on tumor growth was confirmed using xenograft tumor animal models. The results underscored the potential role of M2 macrophage-derived lncRNA NORAD in EVs in NSCLC. SMIM22/GALE promoted glycolysis and the proliferation of NSCLC cells. Furthermore, lncRNA NORAD in EVs targeted SMIM22 and miR-520g-3p in NSCLC cells. Notably, lncRNA NORAD in EVs promoted the proliferation of NSCLC cells and facilitated NSCLC tumor growth through the miR-520g-3p axis. In conclusion, M2 macrophage-derived lncRNA NORAD in EVs promotes NSCLC progression through the miR-520g-3p/SMIM22/GALE axis.

Abstract Pipe contaminant detection holds considerable importance within various industries, such as the aviation, maritime, medicine, and other pertinent fields. This capability is beneficial for forecasting equipment potential failures, ascertaining operational situations, timely maintenance, and lifespan prediction. However, the majority of existing methods operate offline, and the detectable parameters online are relatively singular. This constraint hampers real-time on-site detection and comprehensive assessments of equipment status. To address these challenges, this paper proposes a sensing method that integrates an ultrasonic unit and an electromagnetic inductive unit for the real-time detection of diverse contaminants and flow rates within a pipeline. The ultrasonic unit comprises a flexible transducer patch fabricated through micromachining technology, which can not only make installation easier but also focus the sound field. Moreover, the sensing unit incorporates three symmetrical solenoid coils. Through a comprehensive analysis of ultrasonic and induction signals, the proposed method can be used to effectively discriminate magnetic metal particles (e.g., iron), nonmagnetic metal particles (e.g., copper), nonmetallic particles (e.g., ceramics), and bubbles. This inclusive categorization encompasses nearly all types of contaminants that may be present in a pipeline. Furthermore, the fluid velocity can be determined through the ultrasonic Doppler frequency shift. The efficacy of the proposed detection principle has been validated by mathematical models and finite element simulations. Various contaminants with diverse velocities were systematically tested within a 14 mm diameter pipe. The experimental results demonstrate that the proposed sensor can effectively detect contaminants within the 0.5−3 mm range, accurately distinguish contaminant types, and measure flow velocity.

Abstract The loss of electronic medical records has seriously affected the practical application of biomedical data. Therefore, it is a meaningful research effort to effectively fill these lost data. Currently, state-of-the-art methods focus on using Generative Adversarial Networks (GANs) to fill the missing values of electronic medical records, achieving breakthrough progress. However, when facing datasets with high missing rates, the imputation accuracy of these methods sharply deceases. This motivates us to explore the uncertainty of GANs and improve the GAN-based imputation methods. In this paper, the GRUD (Gate Recurrent Unit Decay) network and the UGAN (Uncertainty Generative Adversarial Network) are proposed and organically combined, called UGAN-GRUD. In UGAN-GRUD, it highlights using GAN to generate imputation values and then leveraging GRUD to compensate them. We have designed the UGAN and the GRUD network. The former is employed to learn the distribution pattern and uncertainty of data through the Generator and Discriminator, iteratively. The latter is exploited to compensate the former by leveraging the GRUD based on time decay factor, which can learn the specific temporal relations in electronic medical records. Through experimental research on publicly available biomedical datasets, the results show that UGAN-GRUD outperforms the current state-of-the-art methods, with average 13% RMSE (Root Mean Squared Error) and 24.5% MAPE (Mean Absolute Percentage Error) improvements.

Abstract Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.

With the continuous development of experimental biology, the limitations of commonly utilized model organisms are becoming increasingly apparent. Discrepancies between research conducted on laboratory animals and humans significantly impede the translational application of findings derived from animal experiments. This review introduces ascidian Ciona intestinalis as a novel model organism, an invertebrate that is evolutionarily closest to vertebrates and is a sister group to vertebrates. The review summarizes recent research progress on Ciona intestinalis in various fields to illustrate the significant advantages and promising application prospects of it as a model organism. The research progress outlined in the review mainly encompasses: (1) The whole-genome sequencing of Ciona intestinalis has been determined and numerous related databases have been established. Various embryonic gene editing technologies have been successfully applied, making it an animal model easy to manipulate genetically and study the functions and interactions of target genes visually. (2) In the field of neurobiology, Ciona intestinalis boasts a central nervous system structure similar to that of vertebrates and possesses numerous homologous neuropeptides and hormone molecules. These features grant it an edge in exploring the mechanisms and functional evolution of endocrine and neuroendocrine-related molecules. Additionally, the sensitivity and habituation of its larvae to light stimulation provide an avenue for exploring mechanisms related to behavioral plasticity. (3) In the field of immunology, Ciona intestinalis possesses a mature innate immune system and has evolved precursor genes to the adaptive immune system, with a relatively simple coding of immune-related genes. These features make it an exemplary model organism for immunological studies. (4) In the field of developmental biology, many studies have focused on the notochord development process in Ciona intestinalis and the regulatory mechanisms of gene expression within it, indicating common evolutionary developmental strategies among chordates. Additionally, insights into its heart development also significantly enhance our comprehension on the genetic network of human heart development. (5) In medical research, the ability of Ciona intestinalis to regenerate its neural complex and siphon, as well as the resilience of its heart to recover contractile function from substantial damage, renders it a valuable animal model for the study of regeneration and heart injury. It also has unique advantages as a research model for Alzheimer's disease and new drug development. Furthermore, its brief five-month lifespan facilitates the observation and recording of the entire aging process and the exploration of the effects of various factors on aging. In summary, this review aims to demonstrate that Ciona intestinalis stands out as a model organism with unique attributes and is expected to play a significant role in a wider range of scientific research areas.

Expansion of renewable energy could help realize the goals of peaking carbon dioxide emissions and carbon neutralization. Some existing grid dispatching methods integrating short-term renewable energy prediction and reinforcement learning (RL) have been proven to alleviate the adverse impact of energy fluctuations risk. However, these methods omit long-term output prediction, which leads to stability and security problems on optimal power flow. This paper proposes a confidence estimation Transformer for long-term renewable energy forecasting in reinforcement learning-based power grid dispatching (Conformer-RLpatching). Conformer-RLpatching predicts long-term active output of each renewable energy generator with an enhanced Transformer to ensure stable operation of the hybrid energy grid and improve the utilization rate of renewable energy, thus boosting dispatching performance. Furthermore, a confidence estimation method is proposed to reduce the prediction error of renewable energy. Meanwhile, a dispatching necessity evaluation mechanism is put forward to decide whether the active output of a generator needs to be adjusted. Experiments carried out on the SG-126 power grid simulator show that Conformer-RLpatching achieves great improvement over the second best algorithm DDPG in security score by 25.8% and achieves a better total reward compared with the golden medal team in the power grid dispatching competition sponsored by State Grid Corporation of China under the same simulation environment. Codes are outsourced in https://github.com/BUPT-ANTlab/Conformer-RLpatching.

BAK and BAX execute intrinsic apoptosis by permeabilising the mitochondrial outer membrane. Their activity is regulated through interactions with pro-survival BCL-2 family proteins and with non-BCL-2 proteins including the mitochondrial channel protein VDAC2. VDAC2 is important for bringing both BAK and BAX to mitochondria where they execute their apoptotic function. Despite this important function in apoptosis, while interactions with pro-survival family members are well characterised and have culminated in the development of drugs that target these interfaces to induce cancer cell apoptosis, the interaction between BAK and VDAC2 remains largely undefined. Deep scanning mutagenesis coupled with cysteine linkage identified key residues in the interaction between BAK and VDAC2. Obstructive labelling of specific residues in the BH3 domain or hydrophobic groove of BAK disrupted this interaction. Conversely, mutating specific residues in a cytosol-exposed region of VDAC2 stabilised the interaction with BAK and inhibited BAK apoptotic activity. Thus, this VDAC2-BAK interaction site can potentially be targeted to either inhibit BAK-mediated apoptosis in scenarios where excessive apoptosis contributes to disease or to promote BAK-mediated apoptosis for cancer therapy.

Abstract Background Reliable pre-surgical prediction of spreading through air spaces (STAS) in primary lung cancer is essential for precision treatment and surgical decision-making. We aimed to develop and validate a dual-delta deep-learning and radiomics model based on pretreatment computed tomography (CT) image series to predict the STAS in patients with lung cancer. Method Six hundred seventy-four patients with pre-surgery CT follow-up scans (with a minimum interval of two weeks) and primary lung cancer diagnosed by surgery were retrospectively recruited from three Chinese hospitals. The training cohort and internal validation cohort, comprising 509 and 76 patients respectively, were selected from Shanghai Chest Hospital; the external validation cohorts comprised 36 and 53 patients from two other centers, respectively. Four imaging signatures (classic radiomics features and deep learning [DL] features, delta-radiomics and delta-DL features) reflecting the STAS status were constructed from the pretreatment CT images by comprehensive methods including handcrafting, 3D views extraction, image registration and subtraction. A stepwise optimized three-step procedure, including feature extraction (by DL and time-base radiomics slope), feature selection (by reproducibility check and 45 selection algorithms), and classification (32 classifiers considered), was applied for signature building and methodology optimization. The interpretability of the proposed model was further assessed with Grad-CAM for DL-features and feature ranking for radiomics features. Results The dual-delta model showed satisfactory discrimination between STAS and non-STAS and yielded the areas under the receiver operating curve (AUCs) of 0.94 (95% CI, 0.92–0.96), 0.84 (95% CI, 0.82–0.86), and 0.84 (95% CI, 0.83–0.85) in the internal and two external validation cohorts, respectively, with interpretable core feature sets and feature maps. Conclusion The coupling of delta-DL model with delta-radiomics features enriches information such as anisotropy of tumor growth and heterogeneous changes within the tumor during the radiological follow-up, which could provide valuable information for STAS prediction in primary lung cancer.

The temperature changes of grain piles during rice storage in high-temperature and high-humidity grain storage areas were studied under the air-conditioning temperature control mode with a temperature of 22 ℃ and a daily opening time of 13 h and a temperature of 24 ℃ and a daily opening time of 24 h. The changes of rice moisture and fatty acid values ​​before and after temperature-controlled storage were compared, and the differences in temperature changes in each layer in the horizontal direction of grain piles at different depths were analyzed. The results showed that the average temperature and the maximum grain temperature of the grain pile increased slowly under different air-conditioning operation modes. Air-conditioned temperature-controlled grain storage had a greater impact on the surface temperature of the grain pile, but less impact on the middle layer grain temperature. During the air-conditioned temperature-controlled storage period, the lower layer grain temperature may be affected by the floor temperature. The temperature control mode that lowered the temperature control temperature but shortened the temperature control time was more economical and efficient. The temperature control mode of 22 ℃ + 13 h could save about 12.4% of electricity costs compared with the temperature control mode of 24 ℃ + 24 h. At the same time, the control effect of the warehouse temperature, surface grain temperature and average grain temperature of the grain pile with a lower basic grain temperature was more obvious, and the basic grain temperature of the grain pile played an important role in the implementation of temperature-controlled grain storage technology.

Major pathologic remission (MPR, residual tumor

Carbon capture, utilization and storage (CCUS) are the key technologies to address global warming. CCUS technologies reduce the CO_2 content in the atmosphere by CO_2 capture and storage. Replacing the use of fossil fuels with CO_2 could further reduce the net emission of CO_2. The applications of CCUS technologies strongly rely on the comprehensive studies of the physical and chemical processes involving CO_2 at micro scale. Microfluidics provides a platform to manipulate fluids at micro or nano scale and reveals the laws of fluid motion. Microfluidics plays an important role in the whole process of CCUS. This review summarizes the advantages of microfluidic technology, including precise manipulation of fluid, large specific surface area and enhanced heat and mass transfer. The applications of microfluidics in CCUS are introduced in detail. Applications of microfluidics for CO_2 capture include the rapid screening of CO_2 adsorbents, formulation optimization and material preparation, while those for CO_2 utilization mainly consist of electrocatalytic CO_2 reduction reaction (CO_2RR), photocatalytic CO_2RR, catalyst preparation and photosynthesis. The microfluidics for CO_2 geosequestration is mainly associated with fluid dynamic analysis and geological model construction. Finally, the challenge and opportunity of microfluidics in the field of CCUS are summarized and outlooked.

Based on the water quality monitoring data in the spring, summer and autumn of 2018 in Xiamen Bay, this study used the fuzzy comprehensive evaluation method to comprehensively evaluate the water quality. The results showed that the Western sea area of Xiamen, Tong'an Bay and Jiulong River estuary were seriously polluted areas, which were class Ⅳ water bodies; the water quality of southern sea area, eastern sea area and Dadeng sea area was in good condition, mainly class Ⅰ water body; DIN and DIP were the main pollutants affecting the water quality of Xiamen Bay; using the area ratio method on the basis of the results obtained by the fuzzy comprehensive evaluation method, the results showed that in 2018, Xiamen Bay as a whole was in Class Ⅲ water body condition, and the water quality needed to be further improved.

Glioblastoma stem-like cells (GSCs) contribute to therapeutic resistance and recurrence of glioblastomas. Here the authors show that Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) promotes GSCs invasion.

AIM: To compare the visual quality between smart pulse technology-assisted(SPT)transepithelial photorefractive keratectomy(TransPRK)of 1 050Hz ablation frequency and small incision lenticule extraction(SMILE)for myopia and astigmatism.METHODS: A total of 138 cases(248 eyes)who received corneal refractive surgery in the Eye Hospital of Chengdu University of TCM were enrolled from July 2020 to January 2021. The patients were divided into TransPRK group(64 cases, 123 eyes)and SMILE group(74 cases, 125 eyes)according to the surgical method. The follow-up duration was 6mo. Strehl ratio(SR)and high-order aberration at 6mm pupil diameter measured by Sirius anterior segment integrated analyzer and LogMAR visual acuity were recorded at different preoperative and postoperative time points.RESULTS: The uncorrected visual acuity(UCVA)of TransPRK group was worse than SMILE group at 1wk and 1mo after surgery(all P

The design of 3D scenes is of great significance, and one of the crucial areas is interior scene design. This study not only pertains to the living environment of individuals but also has applications in the design and development of virtual environments. Previous work on indoor scenes has focused on understanding and editing existing indoor scenes, such as scene reconstruction, segmentation tasks, texture, object localization, and rendering. In this study, we propose a novel task in the realm of indoor scene comprehension, amalgamating interior design principles with professional evaluation criteria: 3D indoor scene design assessment. Furthermore, we propose an approach using a transformer encoder–decoder architecture and a dual-graph convolutional network. Our approach facilitates users in posing text-based inquiries; accepts input in two modalities, point cloud representations of indoor scenes and textual queries; and ultimately generates a probability distribution indicating positive, neutral, and negative assessments of interior design. The proposed method uses separately pre-trained modules, including a 3D visual question-answering module and a dual-graph convolutional network for identifying emotional tendencies of text.

Algal blooms caused by eutrophication are a major global problem, and the monitoring and prediction of algal densities in lakes are important indicators of eutrophication management. However, the reliability of the commonly used chlorophyll-a (Chl-a) to characterize phytoplankton density in lake environments needs to be further investigated. In this paper, we sampled and analyzed 365 samples from nine plateau lakes in Yunnan Province during the dry and rainy seasons. The Chl-a data measured by the laboratory spectrophotometric method and the portable YSI multi-parameter water quality meter (YSI) directly used in the field were compared, and regression analysis and correlation analysis with phytoplankton density were performed. Most of the Chl-a values measured by the laboratory instrument were greater than those measured by the YSI, and the correlation between the two methods was weak (0.492, p < 0.001). The correlation between Chl-a and phytoplankton density measured by the YSI reached 0.67 (p < 0.001) in the dry season, while the laboratory methods used to measure Chl-a to characterize phytoplankton density may have led to an overestimation of phytoplankton density due to nonspecific sources of Chl-a. However, both methods are relatively inaccurate for characterizing phytoplankton density. For different trophic states of lakes, nutrient concentration changes affect the Chl-a concentration of phytoplankton. During different seasons, changes in the fluorescence intensity of phytoplankton in response to environmental conditions prevent the YSI results from reflecting the authentic phytoplankton density. Furthermore, high species diversity can lead to inconsistent changes in Chl-a and phytoplankton because the content of Chl-a in individual cells of different phytoplankton is different. The relationship between Chl-a and phytoplankton density was species specific. Therefore, when applying Chl-a to characterize phytoplankton density in lakes, it is necessary to consider environmental conditions, phytoplankton community structure and other practical conditions. In addition, laboratory analytical methods and instrumental techniques and instruments need to be improved.

IntroductionClimate is crucial factor influencing species distribution, and with global climate change, the potential geographic distribution of species will also alter. In this study, three subtropical tree species (Cunninghamia lanceolata, Pinus taiwanensis, and Quercus glauca) of great ecological values were selected as research objects.MethodsWe applied a maximum entropy (MaxEnt) to predict their potential distributions under different climate scenarios in both present and future conditions based on 37 environmental factors. Jackknife test was used in key factors affecting species distribution. In addition, we explored the key environmental variables that affect their distributions and revealed the evolutionary patterns and migration trends of these tree species under future climate.ResultsThe main findings are as follows: (1) Winter temperature, winter precipitation, and annual temperature range are identified as the key environmental variables affecting the potential geographic distribution of the three tree species; moreover, precipitation-related factors have a greater impact than temperature-related factors; (2) Currently suitable habitats for these three tree species are primarily located in subtropical China with decreasing suitability from south to north; (3) Under future climate conditions, the area of potentially suitable habitat for C. lanceolata continues to expand, while P. taiwanensis and Q. glauca tend to experience a reduction due to increasing greenhouse gas emissions over time; and (4) The centroid of suitable habitat for C. lanceolata shifts northward under future climate change, while the centroid of P. taiwanensis and Q. glauca move southward along with shrinking suitable habitat area.DiscussionOur predictions highlight a high risk of habitat loss of Q. glauca under climate change, recommending management and conservation references for these three commonly used afforestation species under current and future climate change scenarios in China.

Abstract Background: The WHO recommends artemisinin-based combination regimens for uncomplicated Plasmodium falciparum malaria. One such combination is artemisinin-piperaquine tablets (ATQ). ATQ has outstanding advantages in anti-malarial, such as good efficacy, fewer side effects, easy promotion and application in deprived regions. However, the data about the reproductive and endocrine toxicity of ATQ remains insufficient. Thus, we assessed the potential effects of ATQ and its individual components artemisinin (ART) and piperaquine (PQ) on the reproductive and endocrine systems in Wistar rats. Methods: The unfertilized female rats were intragastric administrated with ATQ (20, 40, and 80 mg/kg), PQ (15, 30, and 60 mg/kg), ART (2.5, 5, and 10 mg/kg), or water (control) for 14 days, respectively. The estrous cycle and serum levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), prostaglandin (PG), and adrenocorticotropic hormone (ACTH) were determined. The weights of the kidney, adrenal gland, uterus, and ovaries were measured. The histopathological examinations of the adrenal gland, ovary, uterus, and mammary gland were performed. Results: Compared with the control group, there were no significant differences in the examined items of female rats in the ART groups, including general observation, estrous cycle, hormonal level, organ weight, and histopathological examination. The estrous cycle of female rats was disrupted within 4–7 days after ATQ or PQ administration, and then in a persistent dioestrus phase. At the end of administration, ATQ and PQ at three doses induced decreased PG, increased ACTH, increased adrenal weight and size, and pathological lesions in the adrenal gland and ovary, including vasodilation and hyperemia in the adrenal cortex and medulla as well as hyperplasia and vacuolar degeneration, ovarian corpus luteum surface hyperemia, numerous but small corpus luteum, and disordered follicle development. But the serum levels of E2, FSH, LH, and PRL did not change obviously. These adverse effects in ATQ or PQ treated rats could not completely disappear after 21 days of recovery. Conclusion: Based on the results of this study, ART had no obvious reproductive and endocrine effects on female rats, while ATQ and PQ caused adrenal hyperplasia, increased ACTH, decreased PG, blocked estrus, corpus luteum surface hyperemia, and disrupted follicle development in female rats. These events suggest that ATQ and PQ may interfere with the female reproductive and endocrine systems, potentially reducing fertility.

Infertility and menstrual abnormalities in endometriosis patients are frequently caused by aberrant follicular growth or a reduced ovarian reserve. Endometriosis typically does not directly harm the oocyte, but rather inhibits the function of granulosa cells, resulting in a decrease in oocyte quality. Granulosa cells, as oocyte nanny cells, can regulate meiosis, provide the most basic resources required for oocyte development, and influence ovulation. Endometriosis affects oocyte development and quality by causing granulosa cells apoptosis, inflammation, oxidative stress, steroid synthesis obstacle, and aberrant mitochondrial energy metabolism. These aberrant states frequently interact with one another, however there is currently relatively little research in this field to understand the mechanism of linkage between abnormal states.

Anoikis and epithelial-mesenchymal transition (EMT) are significant phenomena occurring in distant metastasis of colon adenocarcinoma (COAD). A comprehensive understanding of their crosstalk and the identification of key genes are vital for treating the distant metastasis of COAD. The objective of this study was to design and validate accurate prognostic predictors for COAD patients based on the anoikis and EMT processes. We obtained gene signatures from various databases and performed univariate and multivariate Cox regression analyses, principal component analysis (PCA). The COAD patients were categorized into the worst prognosis group, the Anoikis Potential Index (API) Low + EMT Potential Index (EPI) High group and the others group. Then we utilized gene set enrichment analysis (GSEA) to identify differentially expressed genes and to establish a prognostic risk model. The model classified patients into high- or low-risk groups, with patients in the high-risk group displaying worse survival status. A nomogram was established to predict overall survival rates, demonstrating high specificity and sensitivity. Additionally, we connected the risk model to the tumor microenvironment (TME) using single-sample GSEA and the MCP counter tool, as well as evaluated the sensitivity to common chemotherapeutic drugs, such as Gefitinib and Gemcitabine. Lastly, cell and tissue experiments suggested a positive correlation among anoikis resistance, EMT, and liver/lung metastasis of COAD. This is the first study to comprehensively analyze the crosstalk between anoikis and EMT and offers new therapeutic targets for COAD metastasis patients.

Due to the use of the new line and the new station area, the existing tower naming plate has not met the requirements of the latest specification, and it is urgent to replace it in batches, but the traditional naming plate pasting work must be carried out manually throughout the whole process, which is time-consuming and laborious, and the efficiency is low. In order to solve the above problems, a portable retractable tower naming plate pasting device was developed to improve the on-site pasting working mode, and the device integrates a fixed fixture, a cleaning brush, and a retractable insulating rod in one, and has the characteristics of portability and high efficiency. It has been proved in practice that the developed device can effectively reduce the unqualified rate of pasting and improve work efficiency, and effectively improve quality and efficiency.

ObjectiveTo understand the mental health status and its influencing factors among patients with non-tuberculous mycobacterial disease and to provide a reference for medical staff to formulate scientific and feasible intervention strategies.MethodsA total of 114 patients diagnosed with non-tuberculous mycobacillosis during hospitalization in the Department of Infection from September 2020 to April 2021 were selected as the research participants. Participants’ mental health status and related factors were evaluated using a self-made general patient information questionnaire, self-rating Anxiety Scale (SAS), and self-rating Depression Scale (SDS).ResultsAmong 114 patients with non-tuberculous mycosis, 61 (53.51%) exhibited depressive symptoms, and the SDS score was 51.15 ± 13.04, which was higher than the national norm of 41.88 ± 10.57 (p

ObjectiveWhile several initiatives, including monetary rewards and performance system reform, are used to inspire medical staff, none are fully effective. We sought to describe the intrinsic drive of medical staff and identify elements that improve work enthusiasm by increasing internal motivation.MethodsA cross-sectional study was conducted in which 2,975 employee representatives from 22 municipal hospitals in Beijing, China were interviewed using a self-made intrinsic motivation scale for medical staff which includes the achievement motivation, self-efficacy, conscientiousness, gratitude level and perceived organizational support. The Kruskal-Wallis analysis of variance and multiple linear regression methods were used to investigate the level of intrinsic motivation and identify any influencing factors. The correlation between employee drive and turnover intention was determined using Spearman rank correlation analysis and Kendall’s tau b rank correlation coefficient.ResultsA total of 2,293 valid answers were obtained, with a valid recovery rate of 77.1%. There were statistically significant differences in intrinsic motivation and its five dimensions by marital status, political status, profession, service year, monthly income, number of working hours per week, and turnover intention (p

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

The generation and topological configuration of double-layered polarization singularity array (PSA) having paired C-points of opposite topological index through superposing three Laguerre-Gaussian (LG) component beams with orthogonal linear polarization states are demonstrated. The generated PSA beam exhibits diversity in topological geometry and intensity pattern. The topological rule that the zero net topological charge and helicity conservation hold for the entire PSA is also confirmed. Based on our experiment setup consisting of a computer-controlled spatial light modulator (SLM), the PSA morphology can be flexibly customized and dynamically regulated by modulating the parameters of constituent beams. Our scheme provides a convenient device for manipulating polarization singularities and can facilitate the potential applications of singular optics.

The selective acylation of indoles often requires sensitive and reactive acyl chloride derivatives. Here, we report a mild, efficient, functional group tolerant, and highly chemoselective N-acylation of indoles using thioesters as a stable acyl source. A series of indoleamides have been obtained with moderate to good yields. In addition, heterocycles, such as carbazole, can also be used as nucleophiles in this reaction.

In the fields of optics and photonics, phase-only spatial light modulators (SLMs) play an increasingly important role in wave-front engineering. However, the SLMs are subject to wavefront distortion arising from the imperfection in the birefringence effect and physical structure of modulators. This paper presents a simple self-interference phase calibration method applicable to liquid-crystal SLM. We build an interferometric imaging system based on the Pancharatnam phase-shifting to measure the phase distribution of a light beam coming from SLMs. Two types of phase modulation errors of SLMs can be characterized in the measurement process: the erroneous gamma curve and shape aberration. The former belongs to dynamic phase distortion and is measured through a four-step Pancharatnam phase-shifting interference, which allows a one-shot recording of interference pattern via a polarization camera; the latter represents static phase distortion and is extracted from the interference between light waves coming from different regions of the SLM panel by using Zernike polynomial fitting. Our method has the advantages of high-precision pixel-wise phase correction and robustness against environmental disturbance and thus can facilitate the applications of SLM in optical field manipulation.

This paper presents an in-depth study and analysis of evidence-based care in continuous renal replacement therapy for severe pancreatitis and examines the effects of serum procalcitonin (PCT), C-reactive protein (CRP) levels, and CYP2C19 genotyping. Eighty patients with severe pancreatitis who met the inclusion criteria were randomly assigned to the medium metabolic group and the slow metabolic group according to their CYP2C19 gene test results, and then the two groups were randomly divided into the control group and the observation group according to the different treatment regimens. Group 1 was CYP2C19 gene intermediate metabolism and was given to the control group; group 2 was CYP2C19 gene intermediate metabolism and was given to the observation group; group 3 was CYP2C19 gene slow metabolism and was given to the control group; group 4 was CYP2C19 gene slow metabolism and was given to the observation group. The number of cases in each group was 20, and follow-up was taken, but enteral nutrition also has some complications, such as feeding intolerance, if clinicians and nursing staff actively give effective care, it can significantly reduce the incidence of complications, and improve the value of enteral nutrition, shorten the hospitalization time, and improve the clinical prognosis. The relationship between serum CRP and PCT levels and Spatially Oriented Format for Acoustics (SOFA) score and the type of Virtual Access Point (VAP) pathogens and prognosis was investigated by Spearman correlation analysis. Finally, Pearson correlation analysis was used to investigate the relationship between serum CRP and PCT levels and SOFA scores in VAP patients. Based on the above analysis, the clinical value of CRP, PCT levels, and SOFA scores in VAP was evaluated. Several evidence-based guidelines were developed to provide clear recommendations and guidance for the preventive management of enteral nutrition feeding intolerance, but there is a gap between clinical care practice and the best evidence, so the best evidence was introduced. We compare the analysis of the test results with previously reported similar tests, and our results show good accuracy and higher efficiency.

Introduction and Aim. Sentinel lymph node (SLN) mapping has been developed as an alternative to complete lymphadenectomy for the surgical staging of early-stage, uterine-confined endometrial cancer to reduce the morbidity of lymphadenectomy and has been demonstrated as a safe and feasible alternative. We compare the surgical and oncological outcomes between SLN mapping with routine lymphadenectomy in the surgical staging of early-stage endometrial cancer in our centre. Methods. A retrospective single-centre cohort study of patients with early-stage endometrioid endometrial cancer undergoing staging surgery (total hysterectomy, bilateral salpingo-oophorectomy with/without pelvic lymph node, and/or para-aortic lymph node dissection (PLND)) with either SLN mapping or routine lymphadenectomy between July 2017 and December 2018. Results. 203 cases with clinical and radiological International Federation of Gynaecology and Obstetrics (FIGO) stage I endometrioid endometrial cancer were included, out of which 109 cases underwent SLN mapping and 94 cases complete lymphadenectomy. Compared to the PLND group, the SLN group had shorter operative time (129 vs. 162 minutes), less blood loss (100 vs. 300 ml), and decreased length of postoperative hospital stay (3 vs. 4 days) (p

Gancao Xiexin decoction (GCXXD), a well-known classic traditional Chinese medicine prescription, is used to treat various oral ulcers, Behcet disease, gastrointestinal ulcers, etc. However, there is very little information on its safety. This study aimed to investigate the acute and subacute oral toxicity of GCXXD in Sprague-Dawley rats. In the acute toxicity study, rats were orally administered 10 g/kg GCXXD three times a day. Clinical signs of abnormality and mortality were observed daily for 14 days. In the subacute toxicity study, rats were orally administered 0, 1.47, 3.83, or 10 g/kg GCXXD for 28 days. The rats’ clinical signs, body weight, food consumption, hematological and biochemical parameters, bone marrow smear, organ index, and pathological morphology were analyzed. The acute toxicity study showed that GCXXD is safe in rats without any obvious toxicity via an oral dose of 30 g/kg/day (3 × 10 g/kg). After 28 days of administration, slightly decreased RBC, HGB, and HCT were observed in female rats at 10 g/kg, suggesting that repeated doses of high-dose GCXXD may cause mild anemia in female rats. The no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) of oral administration of GCXXD for 28 days in rats are considered to be 3.83 g/kg and 10 g/kg, respectively. Long-term toxicity studies are recommended to strengthen the findings.

Myocyte-driven robots, a type of biological actuator that combines myocytes with abiotic systems, have gained significant attention due to their high energy efficiency, sensitivity, biocompatibility, and self-healing capabilities. These robots have a unique advantage in simulating the structure and function of human tissues and organs. This review covers the research progress in this field, detailing the benefits of myocyte-driven robots over traditional methods, the materials used in their fabrication (including myocytes and extracellular materials), and their properties and manufacturing techniques. Additionally, the review explores various control methods, robot structures, and motion types. Lastly, the potential applications and key challenges faced by myocyte-driven robots are discussed and summarized.

The benefit of immunochemotherapy in treating resectable locally advanced non-small cell lung cancer (NSCLC) is not well established. Here, we report a case of resectable stage III NSCLC treated with neoadjuvant immunotherapy combined with chemotherapy before surgery. A 61 years old man was admitted to our hospital due to paroxysmal cough and was diagnosed as squamous cell carcinoma T4N2M0 in the upper lobe of the right lung, which was locally advanced and resectable. He was treated with 3 courses of paclitaxel 250 mg intravenous (IV), carboplatin 0.65 g IV, and durvalumab 620 mg IV followed by thoracoscopic upper lobectomy and lymph node dissection. There was considerable regression of the tumor before surgery, and the patient achieved a complete pathological response after surgery. Our case study demonstrates the benefit of durvalumab and chemotherapy in the treatment of resectable locally advanced NSCLC.

Objective: To investigate the role of prediction microvascular invasion (mVI) in hepatocellular carcinoma (HCC) by 18F-FDG PET image texture analysis and hybrid criteria combining PET/CT and multi-parameter MRI.Materials and methods: Ninety-seven patients with HCC who received the examinations of MRI and 18F-FDG PET/CT were retrospectively included in this study and were randomized into training and testing cohorts. The lesion image texture features of 18F-FDG PET were extracted using MaZda software. The optimal predictive texture features of mVI were selected, and the classification procedure was conducted. The predictive performance of mVI by radiomics classier in training and testing cohorts was respectively recorded. Next, the hybrid model was developed by integrating the 18F-FDG PET image texture, metabolic parameters, and MRI parameters to predict mVI through logistic regression. Furthermore, the diagnostic performance of each time was recorded.Results: The 18F-FDG PET image radiomics classier showed good predicted performance in both training and testing cohorts to discriminate HCC with/without mVI, with an AUC of 0.917 (95% CI: 0.824–0.970) and 0.771 (95% CI: 0.578, 0.905). The hybrid model, which combines radiomics classier, SUVmax, ADC, hypovascular arterial phase enhancement pattern on contrast-enhanced MRI, and non-smooth tumor margin, also yielded better predictive performance with an AUC of 0.996 (95% CI: 0.939, 1.000) and 0.953 (95% CI: 0.883, 1.000). The differences in AUCs between radiomics classier and hybrid classier were significant in both training and testing cohorts (DeLong test, both p < 0.05).Conclusion: The radiomics classier based on 18F-FDG PET image texture and the hybrid classier incorporating 18F-FDG PET/CT and MRI yielded good predictive performance, which might provide a precise prediction of HCC mVI preoperatively.

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and a star medication used to treat non-small-cell lung carcinomas (NSCLCs). It has caused broad public concern that osimertinib has relatively low stability in plasma. We explored why osimertinib and its primary metabolites AZ-5104 and AZ-7550 are unstable in rat plasma. Our results suggested that it is the main reason inducing their unstable phenomenon that the Michael addition reaction was putatively produced between the Michael acceptor of osimertinib and the cysteine in the plasma matrix. Consequently, we identified a method to stabilize osimertinib and its metabolite contents in plasma. The assay was observed to enhance the stability of osimertinib, AZ-5104, and AZ-7550 significantly. The validated method was subsequently applied to perform the pharmacokinetic study for osimertinib in rats with the newly established, elegant, and optimized ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS) strategy. The assay was assessed for accuracy, precision, matrix effects, recovery, and stability. This study can help understand the pharmacological effects of osimertinib and promote a solution for the similar problem of other Michael acceptor-contained third-generation EGFR-TKI.

Collision-free trajectory planning in narrow spaces has become one of the most challenging tasks in automated parking scenarios. Previous optimization-based approaches can generate accurate parking trajectories, but these methods cannot compute feasible solutions with extremely complex constraints in a limited time. Recent research uses neural-network-based approaches that can generate time-optimized parking trajectories in linear time. However, the generalization of these neural network models in different parking scenarios has not been considered thoroughly and the risk of privacy compromise exists in the case of centralized training. To address the above issues, this paper proposes a hierarchical trajectory planning method with deep reinforcement learning in the federated learning scheme (HALOES) to rapidly and accurately generate collision-free automated parking trajectories in multiple narrow spaces. HALOES is a federated learning based hierarchical trajectory planning method to fully exert high-level deep reinforcement learning and the low-level optimization-based approach. HALOES further fuse the deep reinforcement learning model parameters to improve the generalization capabilities with a decentralized training scheme. The federated learning scheme in HALOES aims to protect the privacy of the vehicle’s data during model parameter aggregation. Simulation results show that the proposed method can achieve efficient automatic parking in multiple narrow spaces, improve planning time from 12.15% to 66.02% compared to other state-of-the-art methods (e.g., hybrid A*, OBCA) and maintain the same level of trajectory accuracy while having great model generalization.

Objective: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown very attractive potential in clinical applications for the treatment of various diseases. However, the data about the reproductive and developmental toxicity of hUC-MSCs remains insufficient. Thus, we assessed the potential effects of intravenous injection of hUC-MSCs on reproduction and development in Sprague-Dawley rats.Methods: In the fertility and early embryonic development study, hUC-MSCs were administered at dose levels of 0, 6.0 × 106, 8.5 × 106, and 1.2 × 107/kg to male and female rats during the pre-mating, mating and gestation period. In the embryo-fetal development study, the pregnant female rats received 0, 6.0 × 106, 1.2 × 107, and 2.4 × 107/kg of hUC-MSCs from gestation days (GD) 6–15. Assessments made included mortality, clinical observations, body weight, food consumption, fertility parameters of male and female, litter, and fetus parameters, etc.Results: No hUC-MSCs-related toxicity was observed on the fertility of male and female rats, and no teratogenic effect on fetuses. hUC-MSCs at 1.2 × 107/kg caused a mildly decrease in body weight gain of male rats, transient listlessness, tachypnea, and hematuria symptoms in pregnant female rats. Death was observed in part of the pregnant females at a dose of 2.4 × 107/kg, which could be due to pulmonary embolism.Conclusion: Based on the results of the studies, the no-observed-adverse-effect levels (NOAELs) are 8.5 × 106/kg for fertility and early embryonic development, 1.2 × 107/kg for maternal toxicity and 2.4 × 107/kg for embryo-fetal development in rats intravenous injected with hUC-MSCs, which are equivalent to 8.5-fold, 12-fold, and 24-fold respectively of its clinical dosage in humans. These findings may provide a rational basis for human health risk assessment of hUC-MSCs.

The position of the nozzle in the jet mechanism of the impulse turbine may cause an eccentric jet due to size processing and installation deviations. To study the effect of jet needle eccentricity on the jet, this article first analyzes the jet characteristics of the jet mechanism with different openings (20, 40, 60, 80, 100%) under 4.8% eccentricity, verify the reliability of the research method in this paper. Then the focus is on the jet characteristics of the jet mechanism at different eccentricities (0, 1, 2.1, 4.8, 8, and 14%) at 40% opening. The results show that as the eccentricity of the nozzle increases, the jet appears to be asymmetrical, and the shape of the jet at the inlet section of the runner gradually changes and becomes an irregular shape. The eccentricity of the water jet increases with the increase of the eccentricity of the needle; the efficiency of the injection mechanism gradually decreases, and the energy loss gradually increases. Before the eccentricity of 4.8%, the efficiency decreases more slowly, and after the eccentricity of 4.8%, the rate of efficiency decrease is accelerated.

Higher amounts of cuticular wax in plants have been associated with improved plant stress tolerance and increased potential for industrial use. In this study, orthologs of KCS1 and CER1 in Arabidopsis, designated BnKCS1-1, BnKCS1-2, and BnCER1-2, were isolated from Brassica napus. Transcription of BnKCS1-1 and BnKCS1-2 in B. napus were induced by abscisic acid (ABA) and drought treatment, while transcription of BnCER1-2 was induced only by drought treatment. All three gene transcripts decreased significantly when plants were treated with methyl jasmonate (MeJA) or subjected to cold stress. Overexpression of BnKCS1-1, BnKCS1-2, and BnCER1-2 under the control of the CaMV35S promoter led to a significant increase in cuticular wax on transgenic B. napus leaves. BnKCS1-1 and BnKCS1-2 overexpression led to similar differences from non-transformed plants, with significantly higher levels of aldehydes (C29 and C30), alkanes (C28, C29, and C31) and secondary alcohols (C28 and C29), and a significantly lower level of C29 ketone. Overexpression of BnCER1-2 led to an increase in alkanes (C27, C28, C29, and C31), a decrease in secondary alcohols (C28 and C29), and insignificant changes in other wax components. Scanning electron microscopy revealed that overexpression of BnKCS1-1, BnKCS1-2, and BnCER1-2 in B. napus resulted in a higher density of wax crystals on the leaf surface than observed in non-transformed plants. Transgenic plants showed a reduced rate of water loss and increased drought tolerance compared to non-transformed plants. These results suggest that BnKCS1-1, BnKCS1-2, and BnCER1-2 gene products can modify the cuticular wax of B. napus. Changing cuticular waxes using transgenic approaches is a new strategy for genetic improvement of plant drought tolerance and provides an opportunity for development of B. napus as a surface-wax crop. Keywords: Brassica napus, Cuticular wax, Drought tolerance, Overexpression, Transformation

Based on the maximum entropy modeling (Maxent) and ArcGIS tool, this study assessed the potential of marginal land and analyzed the impact of environmental variables for Jerusalem artichoke (Helianthus tuberosus L.) in Shaanxi Province, China. The results showed that the dominant land type used for the growth of Jerusalem artichoke was moderately dense grassland. Additionally, significant environmental variables of Jerusalem artichoke and their suitable range in Shaanxi Province were average slope (SLP, 0–5°C), average soil depth (DPT, 1.50–1.60 m), max temperature of the warmest month (Bio5, 30–31°C), annual mean temperature (Bio1, 16.5–18.0°C), precipitation of the wettest quarter (Bio16, 0.01–0.02 m), July solar radiation (SR7, 1.66–1.67 × 107 W/m2), precipitation seasonality (Bio15, 50–60%), precipitation of the driest quarter (Bio17, 0–0.005 m), and isothermality (Bio3, 265–275). Furthermore, the suitable area was mainly distributed in southern (mainly Hanzhong, Ankang, and Shangluo) and northern (mainly Yan’an and Yulin) parts of Shaanxi Province, covering around 8.81 × 1010 m2 and accounting for 42.8% of the total area of the Shaanxi Province. This study can provide a reference for the rational planting of Jerusalem artichoke in Shaanxi Province.

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4′-teterahydroxystilbene-2-O-β-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-β-D-glucoside (EG), and physcion-8-O-β-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.

Clean energy refers to energy that has less impact on the environment and can be used sustainably. With the intensification of global climate change and environmental pollution problems, the development of clean energy has become a common concern for governments and enterprises. In this paper, the scale of carbon emission in Chengdu is measured by analyzing LEAP model, and the carbon sink capacity is measured by the change of land use structure. Based on the trends of carbon sources and sinks, we analyze the countermeasures that Chengdu needs to take to achieve the carbon peak by 2030. Finally, based on the vision of “carbon neutrality”, suggestions are made for the optimization of Chengdu’s territorial spatial planning in terms of building a green and low-carbon territorial spatial development and protection pattern, optimizing the territorial spatial layout and factor allocation, developing clean energy technologies, and increasing the proportion of clean energy use.

Objective: This meta-analysis aimed to systematically assess the therapeutic efficacy and safety of Qinghao Biejia decoction combined with conventional chemical medicine in patients with systemic lupus erythematosus (SLE), and to provide reference for clinical medication.Methods: Multiple databases were retrieved by computer for randomized controlled trials (RCTs) of treating SLE with Qinghao Biejia decoction combining chemical medicine, from the establishment of the database to January 2021. Study screening, data collection, and quality assessment were performed independently by two reviewers. RevMan 5.4 and Stata 15.1 software were used for Meta-analysis.Results: Nine eligible studies, involving 655 SLE participants, were included. Meta-analysis showed that the additional use of Qinghao Biejia decoction superior to chemical medicine alone in people with SLE in improving the overall response rate (RR = 1.30, 95% CI [1.19, 1.41], p < 0.00001, heterogeneity p = 0.61, I2 = 0%), and can decrease SLE Disease Activity Index (SLEDAI) and TCM symptom scores, improve immunological indexes (C3, C4, IgG, IgA, IFN-γ, IL-4, Th1/Th2), reduce the occurrence of adverse events in treatment (P ≤ 0.05).Conclusion: Based on this meta-analysis, the additional use of Qinghao Biejia decoction has more advantages in the treatment of SLE than conventional chemical medication alone, which could enhance the efficacy and reduce adverse reactions, and is worthy of clinical promotion. However, more and higher quality RCTs are still need to confirm our findings.