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Mingyue Wang,1– 4 Xing-Hua Gao,1– 4 Li Zhang1 1Department of Dermatology, the First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2NHC Key Laboratory of Immunodermatology, China Medical University, Shenyang, People’s Republic of China; 3Key Laboratory of Immunodermatology, China Medical University, Ministry of Education, Shenyang, People’s Republic of China; 4National and Local Joint Engineering Research Center of Immunodermatological Theranostics, Shenyang, People’s Republic of ChinaCorrespondence: Li Zhang, Department of Dermatology, the First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China, Email lizhang_1001@126.comAbstract: Atopic dermatitis (AD), a common pruritic and chronic inflammatory skin disease, has a major impact on a patient’s quality of life. It is characterized by dry, itchy, and eczema-like rashes. AD is more prevalent in young children and has been linked to a variety of other allergy disorders. Traditional drug therapy has certain limitations for treating young children with AD. However, biologics have good clinical application prospects in the medical treatment of young patients. Dupilumab, a fully human monoclonal antibody, specifically binds to the IL-4 Rα subunit, inhibiting IL-4 and IL-13 signaling and blocking the occurrence of type 2 inflammatory response. It has a good effect on treating infants and children with moderate-to-severe AD. This review explores the safety and efficacy of dupilumab in the treatment of AD in infants and children and the impact of early intervention on AD progression, with the aim of informing clinical practice in the use of dupilumab for the treatment of young patients with AD.Keywords: atopic dermatitis, dupilumab, infant, child, treatment

Liu CY, Wu JH, Chen ZY, et al. Int J Chron Obstruct Pulmon Dis. 2021;16:2375–2383. The Editor and Publisher of International Journal of Chronic Obstructive Pulmonary Disease are retracting the published article. Concerns were raised that the western blot results in Figure 6 had been duplicated with those from Figure 4 in Chen Z, Zhang Y, Wu J, Gao X, Huang C, Lin Y, Xu X, Li Y. The Mechanism of Penehyclidine Hydrochloride and Its Effect on the Inflammatory Response of Lung Tissue in Rats with Chronic Obstructive Pulmonary Disease During Mechanical Ventilation. Int J Chron Obstruct Pulmon Dis. 2021;16:877–885, https://doi.org/10.2147/COPD.S295329. Both sets of western blots are describing results from different studies. In addition, the image from Figure 2N was found to have been duplicated with the same image from Figure 1N from Chen Zy, Lin Ym, Wu Jh, et al. Effect of doxofylline on pulmonary inflammatory response and oxidative stress during mechanical ventilation in rats with COPD. BMC Pulm Med 22, 66 (2022), https://doi.org/10.1186/s12890-022-01859-6. The authors did not respond to our queries and as the findings could not be verified the Editor and Publisher made the decision to retract the article. The authors were notified of this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Chu-Yun Liu,1 Jian-Hua Wu,1 Zhi-Yuan Chen,1 Yi Zhang,1 Chun-Ling Huang,2 Ai-Mei Lin,1 Xiao-Ting Xu,1 Xiao-Hua Gao1 1Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 2Department of Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of ChinaCorrespondence: Zhi-Yuan ChenDepartment of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of ChinaTel +86 595-26655108Fax +86 595-22770258Email chen_tyty@163.comObjective: To evaluate the effect of doxofylline on reducing the inflammatory response in mechanically ventilated rats with chronic obstructive pulmonary disease (COPD).Methods: A total of 40 eight-week-old male Sprague Dawley rats were randomly divided into four groups of 10 rats each: a control group (group C), a model group (group M), a model + natural saline group (group N), and a doxofylline group (group D). Then mechanical ventilation, drug intervention, and the extraction of the experimental material were performed in each group. Pulmonary tissue samples were taken after 120 minutes of mechanical ventilation and the pulmonary histopathological changes and the wet/dry (W/D) weight ratio of the pulmonary tissue were identified. The levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected using an enzyme-linked immunosorbent assay, and the expression levels of c-Jun-N-terminal kinase (JNK) and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected using immunohistochemistry.Results: Compared with group C, the pulmonary histopathology in groups M, N, and D showed typical changes associated with COPD. Furthermore, the W/D weight ratio and levels of TNF-α, JNK, and p-JNK in the pulmonary tissue increased in groups M, N, and D (P < 0.05), while the levels of IL-10 decreased (P < 0.05). Compared with group M, no statistically significant changes in the above indicators were detected in the pulmonary tissue of group N (P > 0.05). Compared with group N, the W/D weight ratio and levels of TNF-α, JNK, and p-JNK in the pulmonary tissue decreased in group D (P < 0.05), while the levels of IL-10 increased (P < 0.05).Conclusion: Doxofylline might attenuate pulmonary inflammatory responses in mechanically ventilated rats with COPD, and the JNK/stress-activated protein kinase signaling pathway is involved in doxofylline’s inhibition of inflammatory responses in the pulmonary tissue of rats with COPD.Keywords: chronic obstructive pulmonary disease, TNF-α, IL-10, JNK, p-JNK

Ping-Xin Qi,1,2,* Jia-Ni Zou,3,* Jian Zhu,2 Bin Huang,4 Er-Ping Xi,2 Xu-Hui Gao2 1School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, People’s Republic of China; 2Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan 430070, People’s Republic of China; 3Department of Radiology, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan 430070, People’s Republic of China; 4The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu-Hui Gao; Er-Ping XiDepartment of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, 627#, Wuluo Road, Wuchang District, Wuhan, Hubei 430070, People’s Republic of ChinaTel +86-13307195757Fax +86-27-50772388Email whzyygxh@126.com; wo5351@126.comAbstract: A 55-year-old man was treated at the village hospital with six months medical history of recurrent chills and fever. Due to the lack of imaging examination, antipyretic and anti-infective medications were given. Although symptomatic treatment can relieve fever symptoms, symptoms easily flare up again two to three days after taking the drug. Later, the patient suffered from fever again during the COVID-19 epidemic and was sent to our hospital for isolation and treatment. During this hospitalization, chest CT examination is mandatory for all patients in order to meet the requirements of epidemic prevention and control. This led to the inadvertent discovery of a large cystic solid mass in the right thoracic cavity communicating with the esophageal lumen. The patient was preliminarily diagnosed as giant midesophageal diverticulum after three-dimensional CT image reconstruction of the chest was reviewed. Considering the patient’s persistent fever with poor nutritional status, we decided to temporarily place two gastric tubes (diverticulum decompression and gastrointestinal nutrition), and antibiotics were used at the same time as another main treatment. However, after the symptoms eased and nutritional status improved, he refused all further treatment. We believe that this patient’s diverticulum is very classic, and the treatment plan is highly integrated with the needs of epidemic prevention and control and achieves a satisfactory therapeutic effect, so we hope to provide colleagues with new diagnosis and treatment enlightenment through this case.Keywords: giant midesophageal diverticulum, symptom, treatment, imaging

Yan-Hong Gao,1,* Shi-Cong Zhu,2,* Ya Xu,3 Shun-Ji Gao,1 Yu Zhang,4 Qun-An Huang,1 Wen-Hong Gao,1 Jian Zhu,5 Hui-Juan Xiang,1 Xu-Hui Gao5 1Department of Ultrasound, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan 430070, People’s Republic of China; 2Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing 400037, People’s Republic of China; 3Department of Respiratory Medicine, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan 430070, People’s Republic of China; 4Department of Pathology, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan 430070, People’s Republic of China; 5Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan 430070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu-Hui Gao; Hui-Juan XiangGeneral Hospital of Central Theater Command of the People’s Liberation Army, 627#, Wuluo Road, Wuchangqu, Wuhan, Hubei 430070, People’s Republic of ChinaTel +86-13871166597Fax +86-27-50772388Email whzyygxh@126.com xhjyxr@126.comPurpose: To explore the clinical value of ultrasound-guided minimally invasive biopsy of breast nodules for diagnosis and treatment of patients with no positive clinical signs on manual breast examination.Methods: We performed a retrospective review of 136 patients with no signs on breast palpation who underwent ultrasound-guided minimally invasive biopsy. A total of 63 patients underwent breast nodule resection from October 2018 to December 2019 at the General Hospital of Central Theater Command of the People’s Liberation Army. Clinical data, including indications for minimally invasive biopsy or resection, pathological and surgical results were retrospectively analyzed.Results: A total of 199 patients were studied; 136 underwent minimally invasive biopsy and 63 underwent resection. No severe surgical complications occurred. Minimally invasive biopsy of breast nodules was superior to resection with respect to operation time, incision length, and postoperative complication rate.Conclusion: Ultrasound-guided minimally invasive biopsy of breast nodules is feasible for treatment of patients with negative breast nodules and can achieve accurate diagnosis and satisfactory resection.Keywords: minimally invasive breast biopsy, diagnosis, breast nodules, benign breast masses

Ying-Jian Song,1 Juan Tan,2 Xin-Huai Gao,1 Li-Xin Wang1 1Department of Respiratory Medicine, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 2Department of Gerontology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China Background: Lung cancer is one of the most common malignant tumors. Despite advances in lung cancer therapies, prognosis of non-small-cell lung cancer is still unfavorable. The aim of this study was to identify the prognostic value of key genes in lung tumorigenesis.Methods: Differentially expressed genes (DEGs) were screened out by GEO2R from three Gene Expression Omnibus cohorts. Common DEGs were selected for Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology enrichment analysis. Protein–­protein interaction networks were constructed by the STRING database and visualized by Cytoscape software. Hub genes, filtered from the CytoHubba, were validated using the Gene Expression Profiling Interactive Analysis database, and their genomic alterations were identified by performing the cBioportal. Finally, overall survival analysis of hub genes was performed using Kaplan–Meier Plotter.Results: From three datasets, 169 DEGs (70 upregulated and 99 downregulated) were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that upregulated DEGs were significantly enriched in cell cycle, p53 pathway, and extracellular matrix–receptor interactions; the downregulated DEGs were significantly enriched in PPAR pathway and tyrosine metabolism. The protein–protein interaction network consisted of 71 nodes and 305 edges, including 49 upregulated and 22 downregulated genes. The hub genes, including AURKB, BUB1B, KIF2C, HMMR, CENPF, and CENPU, were overexpressed compared with the normal group by Gene Expression Profiling Interactive Analysis analysis, and associated with reduced overall survival in lung cancer patients. In the genomic alterations analysis, two hotspot mutations (S2021C/F and E314K/V) were identified in Pfam protein domains.Conclusion: DEGs, including AURKB, BUB1B, KIF2C, HMMR, CENPF, and CENPU, might be potential biomarkers for the prognosis and treatment of lung adenocarcinoma. Keywords: lung adenocarcinoma, prognosis, gene expression profiling, differentially expressed, bioinformatics analysis

There have been anecdotal reports that local hyperthermia was effective in the treatment of viral warts. We conducted a randomized, patient-blinded, placebo-controlled trial to test the effect of local hyperthermia (44 degrees C for 30 min a day for 3 consecutive days plus 2 additional days 2 weeks later) on plantar warts. By the end of 3 months, 53.57% of patients (15/28) in the treatment group and 11.54% of patients (3/26) in the control group were cured ([Formula: see text]). The effect was not influenced by patient age, duration of disease, or number or size of lesions. [ABSTRACT FROM AUTHOR]

Objective: Cervical cancer is the second most common cancer among women worldwide, and over 85% of cervical cancers occur in developing countries such as China. Lack of resources for nationwide cervical cancer screening in China makes vaccination against oncogenic strains of HPV particularly important. Knowledge of age at sexual debut and sexual behavior is essential prior to implementation of a national vaccination program.Methods and Materials: A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China to assess age at sexual debut and sexual behavior. 98.6% of the 11,852 recruited women aged 15-59 years were included in the analysis. Data were collected using a short, nurse-administered questionnaire and analyzed using standard descriptive statistics and survival analysis.Results: In urban areas, more than ten percent of the 15-19 year old age group were already sexually active at the time of interview; this number increased to nearly 44% in the 20-24 year old age group. Chinese young women with an occupation were more likely to be sexually active compared to female students of the same age, irrespective of area of residence. The crude median sexual debut age for the youngest age group was 17 years, earlier than the sexual debut age reported by older cohorts. Younger age cohorts had an earlier menarche age than older cohorts and were more likely to have more sexual partners than older women, and more likely to have partners with more than one female partner.Conclusion: There is a trend towards earlier sexual debut and riskier sexual behaviors in younger age groups of Chinese women. These findings suggest that HPV vaccination of women between the ages of 13 and 15 years, before the completion of national compulsory education, is likely to contribute to the prevention of HPV infection and cervical cancer in China. [ABSTRACT FROM AUTHOR]

To observe the effects of moxibustion on T cells and T cell immunoglobulin and mucin-domain-containing molecule-3/galectin-9 (Tim-3/Gal-9) pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. Thirty Sprague Dawley rats were randomly divided into three groups, including a control group, an RA model group, and a moxibustion group. An RA model was created through the injection of Freund's complete adjuvant. In the moxibustion group, rats were treated with moxibustion at acupoints of "Shenshu" and "Zusanli." A total of three courses of treatment were conducted. Then the thickness of foot pad was measured, joint pathological changes were observed by hematoxylin-eosin (HE) staining, the proportion of CD4 + T and CD8 + T in peripheral blood was detected by flow cytometry, the expression levels of Tim-3 and Gal-9 in synovium were detected by polymerase chain reaction (PCR), and the expressions of CD4 + T and CD8 + T in synovium were detected by immunofluorescence. HE staining showed that the synovial tissue of the control group was smooth and neatly arranged without inflammatory cell infiltration. In the model group, the joint space was narrowed, the synovial tissue had congestion and edema, and a large number of inflammatory cells infiltrated. Compared with the model group, in the moxibustion group, the joint space narrowed with synovium hyperemia and edema, and the level of inflammatory cell infiltration decreased. Flow cytometry showed that compared with the model group, CD4 + T expression in the moxibustion group was downregulated, while CD8 + T expression was upregulated. PCR results showed that compared with the model group, the expressions of Tim-3 and Gal-9 in the moxibustion group were upregulated. Immunofluorescence results showed that compared with the model group, CD4 + T expression in the moxibustion group was decreased, while CD8 + T expression was increased. The results demonstrate that moxibustion not only suppressed the expression of CD4 + T but also promoted the expression of CD8 + T. The anti-inflammatory effect of moxibustion may be related to the regulation of T cell expression through the Tim-3/Gal-9 signaling pathway.

Object: Osteosarcoma is a malignant tumor originating from the bones, commonly found in children and adolescents, especially in rapidly growing bone areas such as the knees and upper arms. In this study, we aim to delineate the evolution and convergence of research themes in osteosarcoma metabolomics over the past decade, identify major contributors, and forecast emerging trends that could direct future research efforts., Method: The bibliometric method has been applied to systematically analyze the literature in the field of osteosarcoma metabolomics. The relevant literatures were collected from the Web of Science Core Collection, spanning from January 1, 2014, to December 31, 2023. Tools such as CiteSpace, Bibliometrix, and VOSviewer were used for the visual analysis of the collected literatures. The focused information includes institutions, journals, countries, authors, keywords, and citations., Result: Various aspects in the field of osteosarcoma metabolism were analyzed. Shanghai Jiao Tong University has published the most papers in the past ten years, followed by Central South University and Zhejiang University. Among the sources, the international journal of molecular sciences publishes the most articles, and oncotarget is the journal with the highest H index. According to Bradford's law, there are 34 core journals identified. A total of 5501 authors participated in the creation of papers in this field. The distribution of authors follows Lotka`s Law, and 85.3% of authors have only one article. 46% of the corresponding authors are from China, but most of these corresponding authors are not good at international cooperation. China also has the largest number of publications, followed by the United States. It can be confirmed that China dominates this field. Among the keywords, "expression" is the keyword that has received the most attention in the past ten years. All keywords can be divided into 9 clusters. Based on the explosive words and hot topics each year, we speculate that future research will focus on the tumor microenvironment, molecular mechanisms and autophagy, targeted therapies and inhibitors., Conclusion: In summary, this study comprehensively analyzed the current state of research in the field of osteosarcoma metabolism through bibliometric methods. The findings revealed the development trends and research hotspots in this field, which may provide valuable references for future research directions., 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 Tu, Liu, Li, Long, Wang, Liu and Gao.)

Background: Osteosarcoma (OS), a bone tumor with high ability of invasion and metastasis, has seriously affected the health of children and adolescents. Many studies have suggested a connection between OS and the epithelial-mesenchymal transition (EMT). We aimed to integrate EMT-Related genes (EMT-RGs) to predict the prognosis, immune infiltration, and therapeutic response of patients with OS., Methods: We used consensus clustering to identify potential EMT-Related OS molecular subtypes. Somatic mutation, tumor immune microenvironment, and functional enrichment analyses were performed for each subtype. We next constructed an EMT-Related risk signature and evaluated it by Kaplan-Meier (K-M) analysis survival and receiver operating characteristic (ROC) curves. Moreover, we constructed a nomogram to more accurately predict OS patients' clinical outcomes. Response effects of immunotherapy in OS patients was analyzed by Tumor Immune Dysfunction and Exclusion (TIDE) analysis, while sensitivity for chemotherapeutic agents was analyzed using oncoPredict. Finally, the expression patterns of hub genes were investigated by single-cell RNA sequencing (scRNA-seq) data analysis., Results: A total of 53 EMT-RDGs related to prognosis were identified, separating OS samples into two separate subgroups. The EMT-high subgroup showed favourable overall survival and more active immune response. Significant correlations were found between EMT-Related DEGs and functions as well as pathways linked to the development of OS. Additionally, a risk signature was established and OS patients were divided into two categories based on the risk scores. The signature presented a good predictive performance and could be recognized as an independent predictive factor for OS. Furthermore, patients with higher risk scores exhibited better sensitivity for five drugs, while no significant difference existed in immunotherapy response between the two risk subgroups. scRNA-seq data analysis displayed different expression patterns of the hub genes., Conclusion: We developed a novel EMT-Related risk signature that can be considered as an independent predictor for OS, which may help improve clinical outcome prediction and guide personalized treatments for patients with OS., 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 Li, Long, Liu, Long and Gao.)

In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC 50 : 1.52±0.19 μmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72±93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the C Brain /C Serum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

HER2-positive (HER2 + ) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2 + mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2 + mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2 + mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2 + mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation., (© 2024. The Author(s).)

High-entropy (HE) materials, celebrated for their extraordinary chemical and physical properties, have garnered increasing attention for their broad applications across diverse disciplines. The expansive compositional range of these materials allows for nuanced tuning of their properties and innovative structural designs. Recent advances have been centered on their versatile photothermal conversion capabilities, effective across the full solar spectrum (300-2500 nm). The HE effect, coupled with hysteresis diffusion, imparts these materials with desirable thermal and chemical stability. These attributes position HE materials as a revolutionary alternative to traditional photothermal materials, signifying a transformative shift in photothermal technology. This review delivers a comprehensive summary of the current state of knowledge regarding HE photothermal materials, emphasizing the intricate relationship between their compositions, structures, light-absorbing mechanisms, and optical properties. Furthermore, the review outlines the notable advances in HE photothermal materials, emphasizing their contributions to areas, such as solar water evaporation, personal thermal management, solar thermoelectric generation, catalysis, and biomedical applications. The review culminates in presenting a roadmap that outlines prospective directions for future research in this burgeoning field, and also outlines fruitful ways to develop advanced HE photothermal materials and to expand their promising applications., (© 2024 Wiley‐VCH GmbH.)

Objectives: The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations., Methods: Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death., Results: There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year., Conclusion: Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision., 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 Yin, Chen, Zhang, Yang, Li, Gao, Shi and Hu.)

Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata , which led to the isolation of ten new orbitides, named drymariamides A-J ( 1 - 10 ). Compounds 2 , 3 , and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey's method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1 - 10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC 50 value of 1.17 ± 0.19 μM.

Purpose: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert ® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality., Methods: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups., Results: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03)., Conclusion: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation., (© 2023. The Author(s).)

Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.

Purpose: Human gut microbiota has been shown to be significantly associated with various inflammatory diseases. Therefore, this study aimed to develop an excellent auxiliary tool for the diagnosis of juvenile idiopathic arthritis (JIA) based on fecal microbial biomarkers., Method: The fecal metagenomic sequencing data associated with JIA were extracted from NCBI, and the sequencing data were transformed into the relative abundance of microorganisms by professional data cleaning (KneadData, Trimmomatic and Bowtie2) and comparison software (Kraken2 and Bracken). After that, the fecal microbes with high abundance were extracted for subsequent analysis. The extracted fecal microbes were further screened by least absolute shrinkage and selection operator (LASSO) regression, and the selected fecal microbe biomarkers were used for model training. In this study, we constructed six different machine learning (ML) models, and then selected the best model for constructing a JIA diagnostic tool by comparing the performance of the models based on a combined consideration of area under receiver operating characteristic curve (AUC), accuracy, specificity, F1 score, calibration curves and clinical decision curves. In addition, to further explain the model, Permutation Importance analysis and Shapley Additive Explanations (SHAP) were performed to understand the contribution of each biomarker in the prediction process., Result: A total of 231 individuals were included in this study, including 203 JIA patients and Non-JIA individuals. In the analysis of diversity at the genus level, the alpha diversity represented by Shannon value was not significantly different between the two groups, while the belt diversity was slightly different. After selection by LASSO regression, 10 fecal microbe biomarkers were selected for model training. By comparing six different models, the XGB model showed the best performance, which average AUC, accuracy and F1 score were 0.976, 0.914 and 0.952, respectively, thus being used to construct the final JIA diagnosis model., Conclusion: A JIA diagnosis model based on XGB algorithm was constructed with excellent performance, which may assist physicians in early detection of JIA patients and improve the prognosis of JIA 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., (Copyright © 2024 Tu, Liao, Long, Li and Gao.)

Osteoporosis is a major public health concern that significantly increases the risk of fractures. The aim of this study was to develop a Machine Learning based predictive model to screen individuals at high risk of osteoporosis based on chronic disease data, thus facilitating early detection and personalized management. A total of 10,000 complete patient records of primary healthcare data in the German Disease Analyzer database (IMS HEALTH) were included, of which 1293 diagnosed with osteoporosis and 8707 without the condition. The demographic characteristics and chronic disease data, including age, gender, lipid disorder, cancer, COPD, hypertension, heart failure, CHD, diabetes, chronic kidney disease, and stroke were collected from electronic health records. Ten different machine learning algorithms were employed to construct the predictive mode. The performance of the model was further validated and the relative importance of features in the model was analyzed. Out of the ten machine learning algorithms, the Stacker model based on Logistic Regression, AdaBoost Classifier, and Gradient Boosting Classifier demonstrated superior performance. The Stacker model demonstrated excellent performance through ten-fold cross-validation on the training set and ROC curve analysis on the test set. The confusion matrix, lift curve and calibration curves indicated that the Stacker model had optimal clinical utility. Further analysis on feature importance highlighted age, gender, lipid metabolism disorders, cancer, and COPD as the top five influential variables. In this study, a predictive model for osteoporosis based on chronic disease data was developed using machine learning. The model shows great potential in early detection and risk stratification of osteoporosis, ultimately facilitating personalized prevention and management strategies., (© 2024. The Author(s).)

Ectropis grisescens Warren is one of the most important pests of tea plants. In this study, data on the development, survival, and fecundity of E. grisescens were collected at 15, 22, and 32 °C and analyzed by using the age-stage, two-sex life table. At 15 °C, the duration of the preadult period of E. grisescens was significantly prolonged (81.06 days), with high mortality (69.0%), and the proportion of emerged female adults was extremely low (7.0%). At 32 °C, the preadult period was significantly shortened (29.12 days), with high preadult mortality (74.0%), and a low proportion of emerged female adults (15.0%). At 22 °C, with low preadult mortality (24.0%), and a high proportion of emerged female adults (26.0%). The overall effects of the shorter preadult duration, higher preadult survival rate, higher proportion of emerged female adults, higher fecundity (F = 350.88 eggs/♀), and higher net reproductive rate (R0 = 91.23 offspring/individual) at 22 °C resulted in the highest values of the intrinsic rate of increase (r = 0.1054 days-1) and finite rate of increase (λ = 1.1112 days-1). Computer simulation showed that E. grisescens populations can increase much faster at 22 °C than at 15 and 32 °C. The weighted population size and cumulative weighted insect-days provided the dynamics necessary for estimating the damage potential of E. grisescens in devising economical pest management programs. Our results demonstrate that populations of E. grisescens were able to develop at a broad range of temperatures and adapt to the high temperatures. These finding can be utilized to improve the management of E. grisescens., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The affinity distribution of the antigen-specific memory B cell (B mem ) repertoire in the body is a critical variable that defines an individual's ability to rapidly generate high-affinity protective antibody specificities. Detailed measurement of antibody affinity so far has largely been confined to studies of monoclonal antibodies (mAbs) and are laborious since each individual mAb needs to be evaluated in isolation. Here, we introduce two variants of the B cell ImmunoSpot ® assay that are suitable for simultaneously assessing the affinity distribution of hundreds of individual B cells within a test sample at single-cell resolution using relatively little labor and with high-throughput capacity. First, we experimentally validated that both ImmunoSpot ® assay variants are suitable for establishing functional affinity hierarchies using B cell hybridoma lines as model antibody-secreting cells (ASC), each producing mAb with known affinity for a defined antigen. We then leveraged both ImmunoSpot ® variants for characterizing the affinity distribution of SARS-CoV-2 Spike-specific ASC in PBMC following COVID-19 mRNA vaccination. Such ImmunoSpot ® assays promise to offer tremendous value for future B cell immune monitoring efforts, owing to their ease of implementation, applicability to essentially any antigenic system, economy of PBMC utilization, high-throughput capacity, and suitability for regulated testing., (© 2024. The Author(s).)

Introduction: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery., Methods: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups., Results: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p &lt; 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p &lt; 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p &lt; 0.05)., Conclusion: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD., (© 2024 S. Karger AG, Basel.)

Objectives: INS068 is a novel, soluble, and long-acting insulin analog. In this study, we evaluated the pharmacokinetics and relative bioavailability of two formulations of INS068 in healthy Chinese subjects: a reference formulation packaged in vials and administered via syringe (R), and a test formulation packaged and administered via pen injector (T). Methods: A randomized, open-label, two-period, two-sequence crossover study was conducted with 24 healthy Chinese subjects. Subjects were randomized and administered subcutaneously in the abdomen at 0.4 U/kg of test or reference INS068 injection according to an open crossover design. INS068 concentrations in the serum were measured using LC-MS/MS, and the pharmacokinetic parameters of maximum concentration (C max ) and area under the concentration-time curve (AUC 0-t and AUC 0-∞ ) were used to evaluate relative bioavailability. Results: After a single dose at 0.4 U/kg, the median T max of INS068 was 12 h for both formulations, and the mean t 1/2 for T and R was 13.0 h and 12.6 h, respectively. The geometric means of C max and AUC 0-∞ were 3.99 nmol/L and 120 h·nmol/L for the T, and 4.05 nmol/L and 117 h·nmol/L for the R, respectively. The geometric mean ratios of C max , AUC 0-t and AUC 0-∞ of T over R were 98.7% (90% CI: 92.7%-105.2%), 102.6% (90% CI: 100.0%-105.3%) and 102.8% (90% CI: 100.1%-105.5%). Conclusion: The overall PK profile of the two formulations of INS068 injection was comparable in healthy subjects, and the pen injector of INS068 had adequate safety and tolerability, supporting it as a new formulation in a phase III study and bridging PK data from early phase clinical trials. Clinical Trial Registration: clinicaltrials.gov, identifier: NCT05336071., Competing Interests: Authors X-HG, KS, and SF were employed by the Jiangsu Hengrui Medicine Co., Ltd. The remaining 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 Chen, Zhang, Ye, Gao, Song, Zhou, Li, Zhao, Shi, Yang, Shen, Feng and Zhao.)

When faced with an unidentified body, identifying the victim can be challenging, particularly if physical characteristics are obscured or masked. In recent years, microbiological analysis in forensic science has emerged as a cutting-edge technology. It not only exhibits individual specificity, distinguishing different human biotraces from various sites of occurrence (e.g., gastrointestinal, oral, skin, respiratory, and genitourinary tracts), each hosting distinct bacterial species, but also offers insights into the accident's location and the surrounding environment. The integration of machine learning with microbiomics provides a substantial improvement in classifying bacterial species compares to traditional sequencing techniques. This review discusses the use of machine learning algorithms such as RF, SVM, ANN, DNN, regression, and BN for the detection and identification of various bacteria, including Bacillus anthracis, Acetobacter aceti, Staphylococcus aureus, and Streptococcus , among others. Deep leaning techniques, such as Convolutional Neural Networks (CNN) models and derivatives, are also employed to predict the victim's age, gender, lifestyle, and racial characteristics. It is anticipated that big data analytics and artificial intelligence will play a pivotal role in advancing forensic microbiology in the future., 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 Xu, Teng, Gao, Zhang, Yan and Qi.)

Objective: To develop a risk prediction model for the recurrence of diabetic foot ulcer (DFU) in diabetic patients and primarily validate its predictive value. Methods: Meta-analysis combined with retrospective cohort study was conducted. The Chinese and English papers on risk factors related to DFU recurrence publicly published in China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and PubMed, Embase, Cochrane Library, and Web of Science, and the search time was from the establishment date of each database until March 31 st , 2022. The papers were screened and evaluated, the data were extracted, a meta-analysis was performed using RevMan 5.4.1 statistical software to screen risk factors for DFU recurrence, and Egger's linear regression was used to assess the publication bias of the study results. Risk factors for DFU recurrence mentioned in ≥3 studies and with statistically significant differences in the meta-analysis were selected as the independent variables to develop a logistic regression model for risk prediction of DFU recurrence. The medical records of 101 patients with DFU who met the inclusion criteria and were admitted to Affiliated Hospital of Guizhou Medical University from January 2019 to June 2022 were collected. There were 69 males and 32 females, aged (63±14) years. The receiver operating characteristic (ROC) curve of the predictive performance of the above constructed predictive model for DFU recurrence was drawn, and the area under the ROC curve, maximum Youden index, and sensitivity and specificity at the point were calculated. Dataset including data of 8 risk factors for DFU recurrence and the DFU recurrence rates of 10 000 cases was simulated using RStudio software and a scatter plot was drawn to determine two probabilities for risk division of DFU recurrence. Using the β coefficients corresponding to 8 DFU recurrence risk factors ×10 and taking the integer as the score of coefficient weight of each risk factor, the total score was obtained by summing up, and the cutoff scores for risk level division were calculated based on the total score × two probabilities for risk division of DFU recurrence. Results: Finally, 20 papers were included, including 3 case-control studies and 17 cohort studies, with a total of 4 238 cases and DFU recurrence rate of 22.7% to 71.2%. Meta-analysis showed that glycosylated hemoglobin >7.5% and with plantar ulcer, diabetic peripheral neuropathy, diabetic peripheral vascular disease, smoking, osteomyelitis, history of amputation/toe amputation, and multidrug-resistant bacterial infection were risk factors for the recurrence of DFU (with odds ratios of 3.27, 3.66, 4.05, 3.94, 1.98, 7.17, 11.96, 3.61, 95% confidence intervals of 2.79-3.84, 2.06-6.50, 2.50-6.58, 2.65-5.84, 1.65-2.38, 2.29-22.47, 4.60-31.14, 3.13-4.17, respectively, P <0.05). There were no statistically significant differences in publication biases of diabetic peripheral neuropathy, diabetic peripheral vascular disease, glycosylated hemoglobin >7.5%, plantar ulcer, smoking, multidrug-resistant bacterial infection, or osteomyelitis ( P >0.05), but there was a statistically significant difference in the publication bias of amputation/toe amputation ( t =-30.39, P <0.05). The area under the ROC curve of the predictive model was 0.81 (with 95% confidence interval of 0.71-0.91) and the maximum Youden index was 0.59, at which the sensitivity was 72% and the specificity was 86%. Ultimately, 29.0% and 44.8% were identified respectively as the cutoff for dividing the probability of low risk and medium risk, and medium risk and high risk for DFU recurrence, while the corresponding total scores of low, medium, and high risks of DFU recurrence were <37, 37-57, and 58-118, respectively. Conclusions: Eight risk factors for DFU recurrence are screened through meta-analysis and the risk prediction model for DFU recurrence is developed, which has moderate predictive accuracy and can provide guidance for healthcare workers to take interventions for patient with DFU recurrence risk.

Introduction: Significant heterogeneity exists within the tumor-infiltrating CD8 T cell population, and exhausted T cells harbor a subpopulation that may be replicating and may retain signatures of activation, with potential functional consequences in tumor progression. Dysfunctional immunity in the tumor microenvironment is associated with poor cancer outcomes, making exploration of these exhausted T cell subpopulations critical to the improvement of therapeutic approaches., Methods: To investigate mechanisms associated with terminally exhausted T cells, we sorted and performed transcriptional profiling of CD8 + tumor-infiltrating lymphocytes (TILs) co-expressing the exhaustion markers PD-1 and TIM-3 from large-volume melanoma tumors. We additionally performed immunologic phenotyping and functional validation, including at the single-cell level, to identify potential mechanisms that underlie their dysfunctional phenotype., Results: We identified novel dysregulated pathways in CD8 + PD-1 + TIM-3 + cells that have not been well studied in TILs; these include bile acid and peroxisome pathway-related metabolism and mammalian target of rapamycin (mTOR) signaling pathways, which are highly correlated with immune checkpoint receptor expression., Discussion: Based on bioinformatic integration of immunophenotypic data and network analysis, we propose unexpected targets for therapies to rescue the immune response to tumors in melanoma., Competing Interests: BG is a consultant/advisory board member for Merck. The remaining 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 Cameron, Richardson, Golden, Phoon, Tamilselvan, Pfannenstiel, Thapaliya, Roversi, Gao, Zagore, Cameron and Gastman.)

Objective: We retrospectively analyzed the occurrence of postoperative delirium following hip surgery and the associated risk factors. The aim was to establish a clinical foundation for preventing postoperative delirium after hip surgery., Methods: We retrospectively selected elderly patients who had hip surgery at our hospital between January 2022 and August 2022. We included patients who experienced delirium in the observation group and those who did not encounter delirium in the control group. We then proceeded to compare various indicators among these two groups of patients., Results: We analyzed a total of 97 cases of hip surgery, and among them, 32 cases experienced postoperative delirium, resulting in an incidence rate of 32.9%. Various factors were found to be linked to the development of postoperative delirium, including age, height, gender (male), preoperative erythrocyte sedimentation rate (ESR), postoperative ESR, preoperative lactate levels, pain scores on the first day after surgery, type of surgical procedure, and the occurrence of delirium in the post-anesthesia care unit (PACU delirium). Additionally, it was observed that 75% of patients who had PACU delirium also experienced postoperative delirium., Conclusion: Postoperative delirium in patients who have hip surgery had an incidence rate of 32.9%. This phenomenon is linked to various factors that pose a risk, such as the patient age, height, gender, preoperative ESR levels, postoperative ESR levels, preoperative lactate levels, pain scores on the day following surgery, and the specific surgical procedure performed. The likelihood of experiencing delirium increases by 12% for every additional 10 years in patient age. Additionally, the occurrence of delirium in the PACU is a strong indicator of the likelihood of experiencing postoperative delirium., 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 Liu, Zhang, Liu, Lu, Wu, Gao and Chen.)

Psoriasis, which is one of the most common skin diseases, involves an array of complex immune constituents including T cells, dendritic cells and monocytes. Particularly, the cytokine IL17A, primarily generated by TH17 cells, assumes a crucial function in the etiology of psoriasis. In this study, a comprehensive investigation utilizing bulk RNA analysis, single-cell RNA sequencing, and spatial transcriptomics was employed to elucidate the underlying mechanisms of psoriasis. Our study revealed that there is an overlap between the genes that are differentially expressed in psoriasis patients receiving three anti-IL17A monoclonal antibody drugs and the genes that are differentially expressed in lesion versus non-lesion samples in these patients. Further analysis using single-cell and spatial data from psoriasis samples confirmed the expression of hub genes that had low expressions in psoriasis tissue but were up-regulated after anti-IL17A treatments. These genes were found to be associated with the treatment effects of brodalumab and methotrexate, but not adalimumab, etanercept, and ustekinumab. Additionally, these genes were predominantly expressed in fibroblasts. In our study, fibroblasts were categorized into five clusters. Notably, hub genes exhibited predominant expression in cluster 3 fibroblasts, which were primarily engaged in the regulation of the extracellular matrix and were predominantly located in the reticular dermis. Subsequent analysis unveiled that cluster 3 fibroblasts also established communication with epithelial cells and monocytes via the ANGPTL-SDC4 ligand-receptor configuration, and their regulation was governed by the transcription factor TWIST1. Conversely, cluster 4 fibroblasts, responsible for vascular endothelial regulation, were predominantly distributed in the papillary dermis. Cluster 4 predominantly engaged in interactions with endothelial cells via MDK signals and was governed by the distinctive transcription factor, ERG. By means of an integrated analysis encompassing bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics, we have discerned genes and clusters of fibroblasts that potentially contribute to the pathogenesis of psoriasis., (© 2023. Springer Nature Limited.)

In the present study, a series of derivatives and analogs of daidzein were designed and synthesized to investigate cholinesterase inhibition and blood-brain barrier permeability. The enzyme assay showed that most of the compounds containing a tertiary amine group exhibit moderate cholinesterase inhibition, 7-hydroxychromone derivatives (absence of B ring of daidzein scaffold) only have a weaker bioactivity, while those compounds without the tertiary amine group have no bioactivity. Among them compound 15a (4'-N,N-dimethylaminoethoxy-7-methoxyisoflavone) appeared the best inhibitory activity (IC 50 : 2.14 ± 0.31 μmol/L) and higher selectivity for AChE over BuChE (Ratio: 7.07). It was selected for the further investigation by UPLC-MS/MS. The results show that C Brain/Serum of compound 15a in mice was more than 2.87 within 240 min. This discovery may provide worthy information for the future development of central nervous drugs including but not limited to cholinesterase inhibitors., (© 2023 John Wiley & Sons Ltd.)

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age ( M (IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n =581) and an extended waiting time group (12 to<20 weeks, n =147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ 2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95% CI : 1.001 to 1.020, P =0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 10 th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ 2 =3.901, P =0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ 2 =10.510, P =0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups ( χ 2 =1.878, P =0.171; χ 2 =0.078, P =0.780; χ 2 =1.265, P =0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.