Search

Yong Qiu, Teng-Jiao Zhang, Zhen Hua Anesthesiology Department, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of ChinaCorrespondence: Zhen HuaAnesthesiology Department, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Dong Dan, Beijing 100730, People’s Republic of ChinaEmail huazhenbj528@163.comBackground: Erector spinae plane block (ESPB) as a new trunk fascia block technique was proposed in 2016. ESPB has aroused the interest of many nerve block experts. However, there are few clinical studies on ESPB for lumbar surgery, and its effectiveness and safety are controversial. The goal of this review is to summarize the use of ESPB for lumbar spine surgery in order to better understand this technique.Methods: PubMed, EMBASE, Cochrane library and ClinicalTrial.gov databases were searched up to July 30, 2019. According to the inclusion and exclusion criteria established in advance, “lumbar spine surgery” and “ESPB” related MesH terms and free-text words were used. Data on pain scores, analgesic consumptions and adverse effects were reported. All processes follow PRISMA statement guidelines.Results: A total of 171 participants from 11 publications were identified, including two randomized controlled trials (RCTs), one retrospective cohort study, four case reports and four cases series. Block operation planes from T8 to L4. The main anesthetics used in the block are bupivacaine, ropivacaine and lidocaine. There was evidence for reducing postoperative pain scores and analgesic consumptions.Conclusion: The effectiveness and safety of ESPB for lumbar spine surgery are still controversial. The current evidence is insufficient to support the widespread use of ESPB for lumbar spine surgery. High-quality RCTs are urgently needed.Keywords: ESPB, lumbar spine surgery, postoperative analgesia

Teng-Jiao Zhang,1,2 Jing-Jing Zhang,1,2 Zong-Yang Qu,1,2 Hong-Ye Zhang,1,2 Yong Qiu,1,2 Zhen Hua1,2 1Department of Anesthesiology, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 2Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Zhen HuaDepartment of Anesthesiology, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Beijing 100730, People’s Republic of ChinaTel/Fax +86 10 8513 6409Email huazhen3038@bjhmoh.cnPurpose: Erector spinae plane block (ESPB) is a newly reported interfascial plane block in pain management, and it can block the nerves exactly in line with the area of the posterior lumbar surgery. The objective of this research was to determine the effectiveness of pre-operative ESPB in enhancing recovery of posterior lumbar surgery.Patients and Methods: A total of 60 patients undergoing open posterior lumbar decompression surgery under general anesthesia were randomized into two groups. T12 group was performed pre-operatively bilateral ESPB with ropivacaine at the T12 level, but control group did not receive the block. The primary outcome was the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score at 10 minutes after extubation. Secondary outcomes included intraoperative sufentanil consumption, postoperative morphine consumption, first time to ambulation after surgery and hospital length of stay after surgery. All participants were followed up to hospital discharge.Results: The mean (SD) MOAA/S scores at 10 minutes after extubation were 4.2 (95% CI, 4.0 to 4.4), and 3.4 (95% CI, 3.2 to 3.6) in the T12 and control groups (P < 0.001), respectively. Intraoperative sufentanil consumption (P =0.007) and postoperative morphine consumption (P =0.003) were lower in the T12 group than in the control group. Although first time to ambulation after surgery was sooner in the T12 group than in the control group (P =0.003), hospital length of stay was similar (P=0.054).Conclusion: Pre-operative bilateral ESPB at T12 can enhance recovery after posterior lumbar surgery and reduce perioperative opioid consumption.Keywords: posterior lumbar surgery, erector spinae plane block, enhanced recovery after surgery, regional anesthesia

Lan Yang,1,2,* Jing-Dong Zhou,2,3,* Ting-Juan Zhang,2,3 Ji-Chun Ma,1,2 Gao-Fei Xiao,1,2 Qin Chen,1,2 Zhao-Qun Deng,1,2 Jiang Lin,1,2 Jun Qian,2,3 Dong-Ming Yao1,2 1Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2The Key Laboratory of Precision Diagnosis and Treatment of Zhenjiang City, Zhenjiang, Jiangsu, People’s Republic of China; 3Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China *These authors contributed equally to this work Background and purpose: Abundant studies have shown that lncRNA PANDAR plays an oncogenic role in human solid tumors. Although abnormal expression of PANDAR has been well investigated in solid tumors, it was rarely studied in hematologic diseases. Hence, the aim of this study was to determine the PANDAR expression level and its clinical significance in patients with acute myeloid leukemia (AML).Materials and methods: For detecting the expression level of PANDAR in 119 AML patients and 26 controls, real-time quantitative PCR was used in this study. The prognostic values were evaluated by using Kaplan–Meier analysis, Cox regression analyses, and logistic regression analysis.Results: PANDAR was significantly overexpressed in AML and might be a promising biomarker which could distinguish AML from normal samples (P

Lei Bai,1,* Zhenqiu Liu,2,3,* Qiwen Fang,2,3 Qiong Yan,4 Oumin Shi,5 Pingping Bao,6 Lina Mu,7 Xingdong Chen,8,9 Tiejun Zhang2,3 1Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China; 2Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China; 3Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China; 4Department of Child and Maternal Health, School of Public Health, Fudan University, Shanghai, China; 5Department of Neurology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China; 6Department of Chronic Non-Communicable Disease Surveillance, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China; 7Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York (SUNY) at Buffalo, Buffalo, NY, USA; 8State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China; 9Fudan University Taizhou Institute of Health Sciences, Taizhou, China *These authors contributed equally to this work Background: In 2012, liver cancer ranked as the fifth and eighth most common cancer in men and women, respectively, in urban Shanghai. This study aims to present the trend and projection of age-specific incidence and mortality of liver cancer in Shanghai.Methods: We extracted data of liver cancer incident cases and deaths between 1973 and 2012. An age–period–cohort model was used to analyze the data.Results: A total of 47,344 men and 18,692 women were diagnosed with liver cancer from 1973 to 2012. The overall age-standardized incidence was 26.89 and 8.89 per 100,000 for men and women, respectively. Correspondingly, a total of 44,355 and 18,084 men and women died from liver cancer during this period. The overall age-standardized death rate was 25.34 per 100,000 in men and 9.39 per 100,000 in women. Between 1973 and 2012, liver cancer incidence and mortality in all age groups, except people aged 0–19 years, experienced a significant decline. Similar temporal patterns were detected in liver cancer mortality in both sexes when compared with incidence. Liver cancer incidence and mortality are expected to further decline among all age groups in 2013–2020 in both sexes, though the numbers of incident cases will remain stable.Conclusion: Incidence and mortality of liver cancer in urban Shanghai have decreased by about 40% and 50%, respectively, over the past four decades. This decline is expected to continue in the near future. However, the population is aging, which is reflected in the increasing crude rates and decreasing age-adjusted rates. Keywords: liver cancer, incidence, mortality, Shanghai

Heng Liu,1 Tijiang Zhang,1 Song Jiao,2 Bangguo Li,1 Jing Guan,1 Yi-Xiang J Wang3 1Department of Radiology, 2Cerebrovascular Diseases Clinic, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, 3Department of Imaging and Interventional Radiology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, People’s Republic of China Background: The purpose of this study was to investigate the epidemiology of sporadic ruptured cerebral aneurysm in the Chinese population. Methods: We retrospectively analyzed the medical records of 264 consecutive Chinese patients admitted to the Affiliated Hospital of Zunyi Medical University of Guizhou Province in Southwest China between December 2012 and March 2015 for spontaneous subarachnoid hemorrhage due to a ruptured cerebral artery aneurysm.Results: The study population comprised 171 females and 93 males with a median age of 50 (range 5–76) years. The female to male ratio was 1.84:1. For both males and females, aneurysm rupture was most common in the 40–49-year age group (34.5%). Most of the ruptured aneurysms were in the size range of 2–5 mm (47.2%), followed by 5–10 mm (43.8%). Ruptured aneurysms occurred most often in the posterior communicating artery (36.6%) or the anterior communicating artery (25.7%). There were more cases of anterior communicating artery aneurysm on the left side (53 [Left side]/16 [Right side]=3.31, P0.05).Conclusion: This study provides valuable information on the epidemiology of ruptured cerebral aneurysm in the Chinese population. Keywords: cerebral aneurysm, rupture, subarachnoid hemorrhage, Chinese population, epidemiology

Background: Receptor-interacting protein kinase 3 (RIPK3) has been implicated in the pathogenesis of diverse human cancers. However, the role of RIPK3 in acute myeloid leukemia (AML) is not fully understood, which needs further research and clarification., Methods: We first identified the expression and clinical prognostic value of RIPK3 in AML through a public database and further validated in our research cohort. In addition, the biological function of RIPK3 in leukemic development was further verified through in vitro experiments., Results: Based on the GEPIA database, we screened that RIPK3 overexpression among RIPK family was associated with poor prognosis in AML. Afterwards, another independent cohort from our research center further confirmed the expression pattern of RIPK3 in AML patients. Clinically, increased RIPK3 expression was closely related to specific subtypes of AML, such as FAB-M4/M5, normal karyotype and NPM1 mutation. The significant association of RIPK3 overexpression with FAB-M4/M5 was further validated in AML cell lines. Notably, AML patients with RIPK3 overexpression received transplantation presented a markedly longer survival than those just receiving chemotherapy, whereas those with RIPK3 underexpression showed similar survival between transplantation and chemotherapy group. Bioinformatics analysis showed the significant association of RIPK3 expression with diverse oncogenes/tumor suppressor genes and tumor-related biological processes in AML. Subsequently, we further performed functional experiments in vitro confirmed the potential oncogenic role of RIPK3 in AML., Conclusions: Overexpression of RIPK3 was associated with specific subtypes of AML, such as FAB-M4/M5, normal karyotype and NPM1 mutation, and may facilitate the leukemic development. Moreover, RIPK3 overexpression was associated poor prognosis, and may guide treatment choice in AML., Competing Interests: Declarations. Ethics approval and consent to participate: The present study approved by the Ethics Committee of the Affiliated People’s Hospital of Jiangsu University (K-20230146-Y). The procedures used are consistent with the principles of the Helsinki Declaration. Written informed consents were obtained from all enrolled individuals prior to their participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The homeobox (HOX) genes especially for HOXA cluster play crucial roles in leukemogenesis. HOXA overexpression caused by genetic alterations, such as KMT2A rearrangements, NUP98- fusions and FLT3-ITD mutations, is frequently identified in AML. However, very few studies determined the DNA methylation-mediated epigenetic regulation of the HOXA cluster genes in AML., Methods: We systematically first screened the prognostic value of HOXA cluster genes methylation in AML from The Cancer Genome Atlas (TCGA) datasets. Afterwards, the candidate prognosis-related gene HOXA9 were selected for clinical relevance analysis and were further validated in another independent cohort from our research center., Results: The methylation of HOXA9, among HOXA cluster genes, negatively correlated with adverse prognosis and expression were screened and identified in AML among TCGA datasets. Clinically, HOXA9 hypomethylation was positively correlated with specific subtypes of AML, such as French-American-British (FAB)-M5/M7, normal karyotype and FLT3, NPM1 and DNMT3A mutation, whereas negatively associated with FAB-M3, t(15;17), t(8;21) and t(16;16). Importantly, AML patients with HOXA9 hypomethylation may profit from transplantation, whereas AML patients with HOXA9 hypermethylation could not, suggesting that HOXA9 methylation may be used to guide therapeutic selection between transplantation and chemotherapy. Bioinformatics analysis demonstrated the association of HOXA9 expression with diverse leukemia-related genes (HOXAs, SOSTDC1, MEG3, miR-10a, miR-381 and miR-193b) and signaling pathways (PI3K-Akt signaling) in AML. Subsequently, we further validate the hypomethylation pattern of HOXA9 in AML patients and the epigenetic regulation of HOXA9 methylation in AML cell-lines., Conclusions: HOXA9 methylation linked to HOXA9 expression correlates with diverse genetic abnormalities of AML, such as normal karyotype, t(15;17), t(8;21), t(16;16) and FLT3, NPM1 and DNMT3A mutations. Moreover, HOXA9 hypomethylation may be associated with adverse prognosis, and may guide treatment choice in AML., Competing Interests: Declarations. Ethical approval and consent to participate: The present study approved by the Ethics Committee of the Affiliated People’s Hospital of Jiangsu University. The procedures used are consistent with the principles of the Helsinki Declaration. Written informed consents were obtained from all enrolled individuals prior to their participation. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

SOX9 is a crucial transcriptional regulator of cartilage development and homeostasis. Dysregulation of SOX9 is associated with a wide spectrum of skeletal disorders, including campomelic dysplasia, acampomelic campomelic dysplasia, and scoliosis. Yet how SOX9 variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four pathogenic variants of SOX9 identified in a cohort of patients with congenital vertebral malformations. We report a pathogenic missense variant in the transactivation middle (TAM) domain of SOX9 associated with mild skeletal dysplasia and scoliosis. We isolated a Sox9 mutant mouse with an in-frame microdeletion in the TAM domain ( Sox9 Asp272del ), which exhibits skeletal dysplasia including kinked tails, rib cage anomalies, and scoliosis in homozygous mutants. We find that both the human missense and the mouse microdeletion mutations resulted in reduced SOX9 protein stability in cell culture, while Sox9 Asp272del mutant mice show decreased SOX9 expression in the growth plate and annulus fibrosus tissues of the spine. This reduction in SOX9 expression was correlated with the reduction of extracellular matrix components, such as tenascin-X and the Adhesion G-protein coupled receptor ADGRG6. In summary, our work identified and modeled a pathologic variant of SOX9 within the TAM domain and demonstrated its importance for SOX9 protein stability. Our work demonstrates that SOX9 stability is important for the regulation of ADGRG6 expression, which is a known regulator of postnatal spine homeostasis, underscoring the essential role of SOX9 dosage in a spectrum of axial skeleton dysplasia in humans., Competing Interests: Competing interests statement:The authors declare no competing interest.

Acetamiprid and pyridaben is a compound pesticide, Due to its characteristics of high efficiency, and environmental safety, it has been widely used in agriculture in recent years.This article reports a case of poisoning from a mixture of pymetrozine and propargite pesticides. The patient experienced severe symptoms of poisoning such as vomiting, shortness of breath, abdominal discomfort, generalized cyanosis, bradycardia, and shock after self-administering the pesticide. After admission to the hospital, the patient was treated with atropine to increase heart rate, endotracheal intubation to assist breathing, and norepinephrine to maintain blood pressure. In addition, the patient received gastric lavage, catharsis, hemoperfusion, and continuous blood purification therapy to eliminate the toxins. The patient was successfully treated and discharged after recovery.

Background: Borreria latifolia (Aubl.) K. Schum (Rubiaceae) is an annual weed with a strong allelopathic inhibitory effect on malignant weeds in orchards in southern China. This study was carried out to investigate its allelopathic potential and to identify allelochemicals present in B. latifolia., Results: Aqueous extracts of B. latifolia inhibited the germination and radicle growth of Eleusine indica and the radicle growth of Bidens alba in a dose-dependent manner. However, only the high-concentration treatment at 50 mg mL -1 delayed the germination of B. alba and Digitaria sanguinalis. Among the root, stem, and leaf aqueous extracts of B. latifolia, the leaf extract had the strongest inhibitory effects on the germination and seedling growth of E. indica, followed by stem extract and then root extract. A total of 47 published allelochemicals, including coumarin, 4-hydroxybenzoate, salicylic acid, 4-hydroxycinnamic acid, and vanillic acid, were identified in the leaf extract. Among the five allelochemicals, coumarin was found to be present in the highest concentration in the leaf extract. Furthermore, coumarin exhibited a significantly greater inhibitory effect on E. indica (EC 50  = 36.87 mg L -1 ) than did the other allelochemicals (EC 50  = 100.87-156.30 mg L -1 )., Conclusion: This study indicates that the leaf extracts of B. latifolia and their allelochemicals have excellent potential as bioherbicides and that coumarin is one of the key allelochemicals in B. latifolia. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Objectives: Understanding the patterns and implications of coexisting musculoskeletal conditions is crucial for developing effective management strategies and improving care for older adults. This study aimed to examine the associations between musculoskeletal multimorbidity burden and trajectory and holistic well-being among middle-aged and older adults., Methods: This prospective study employed data from nine consecutive waves of the English Longitudinal Study of Aging (ELSA), spanning 2002-2018. We used latent class trajectory models (LCTM) to identify groups based on changes in musculoskeletal multimorbidity status. Subsequently, we employed linear mixed models to investigate the associations between musculoskeletal disease burden, trajectory groups, and seven dimensions of holistic well-being: Activities of Daily Living (ADLs), Instrumental Activities of Daily Living (IADLs), depression, memory, loneliness, social interactions, and life satisfaction., Results: In total, 5272 participants (mean age: 71.9 years; SD: 8.9) were included in the final analysis. Four distinct trajectories were identified: a low-burden group (48.37%), an emerging group (14.76%), a moderate-burden group (26.00%), and a persistent burden group (10.87%). After adjustment, the findings demonstrate that the musculoskeletal disorder burden significantly impacts ADLs, depression, memory, social interactions, and life satisfaction in middle-aged and older adults, with minor effects on IADLs and loneliness. Moreover, with the escalation of the burden, its impact significantly intensifies (p for trend is < 0.001). Compared with the low-burden group, participants in both the moderate and persistent burden groups exhibited significantly lower capabilities in ADLs, poorer memory, increased social interactions, and lower life satisfaction. The emerging group displayed a similar trend, though without statistically significant results., Conclusions: Our study suggests that the extent and persistence of musculoskeletal disease burden can significantly affect holistic well-being among middle-aged and older individuals., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background Context: Chronic low back pain (CLBP) is a significant global health burden, primarily affecting the middle-aged and older; However, there is a lack of clear, evidence-based guidelines for leisure-time physical activity aimed at preventing CLBP., Purpose: This study sought to delineate the association between aerobic physical activity (APA) and muscle strengthening activities (MSA) and the prevalence of CLBP., Study Design: This was a population-based study conducted across the United States., Patient Sample: This nationwide study utilizes deidentified data from 22 consecutive rounds of the National Health Interview Survey (NHIS) from 1997 to 2018., Outcome Measures: The primary outcome was self-reported CLBP., Methods: We analyzed the prevalence of CLBP in a representative sample of 324,793 middle-aged and older people. Among 263,871 individuals, we used multiple logistic regression to investigate individual and joint association between the amount of APA and MSA with CLBP., Results: In total, 263,871 participants (mean age, 59.0 years; SD, 9.7) were included in the final analysis. From 1997 to 2018, the prevalence of CLBP was approximately 32%, with an annual increase. Engaging in APA for 75 to 150 minutes weekly was associated with a modest reduction in CLBP risk (OR [95% CI] = 0.97 [0.97-0.98]). Similar benefits were seen with 150 to 225, 225 to 300, and >300 minutes. Engaging in MSA 2 to 3 times and 4 to 5 times weekly also reduced CLBP risk (0.98 [0.98-0.99] and 0.98 [0.97-0.99], respectively). Optimal reductions of CLBP risk may be associated with balanced levels of APA and MSA, with recommended amounts being 225 to 300 min/w of APA and 4 to 5 times/w of MSA (0.92 [0.89-0.95])., Conclusions: The study found engaging in over 75 minutes of APA and 2 to 5 weekly MSA sessions is associated with a reduced risk of CLBP. Furthermore, a balanced combination of APA and MSA may correspond to the greatest reduction in CLBP risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Paraspinal muscle segmentation and reconstruction from MR images are critical to implement quantitative assessment of chronic and recurrent low back pains. Due to unclear muscle boundaries and shape variations, current segmentation methods demonstrate suboptimal performance with insufficient training samples. This work proposes a novel approach to modeling and inferring muscle shapes that enhances segmentation accuracy and efficiency with few training data., Methods: Firstly, a probabilistic shape model (PSM) based on Fourier basis functions and Gaussian processes (GPs) is designed to encode 3D muscle shapes, where anatomical meanings are attributed to the model's geometric parameters. Muscle shape variations and correlations are described by the GPs of the geometric parameters, which allow a small size of parameters to model the distribution of muscle shapes. Secondly, a Bayesian framework is developed to achieve entire muscle segmentation by posterior estimations. The framework fuses the geometric prior of the PSM with observations of deep-learning-based edge detections (DED) and sparse manual annotations, by which issues of unclear boundaries and shape variations can be compensated., Results and Conclusion: Experiments on public and clinical datasets demonstrate that, with just three manually annotated slices, our method achieves a Dice similarity coefficient exceeding 90%, which outperforms other methods. Meanwhile, our method needs only a small training dataset and offers rapid inference speeds in clinical applications., Significance: Our study enables precise assessment of paraspinal muscles in 2D and 3D, aiding clinicians and researchers in understanding muscle changes in various conditions, potentially enhancing treatment outcomes.

Biallelic pathogenic variants in CCN6 cause progressive pseudorheumatoid dysplasia (PPD), a rare skeletal dysplasia. The predominant features include noninflammatory progressive joint stiffness and enlargement, which are not unique to this condition. Nearly 100% of the reported variants are single nucleotide variants or small indels, and missing of a second variant has been reported. Genome sequencing (GS) covers various types of variants and deep phenotyping (DP) provides detailed and precise information facilitating genetic data interpretation. The combination of GS and DP improves diagnostic yield, especially in rare and undiagnosed diseases. We identified a novel compound heterozygote involving a disease-causing copy number variant (g.112057664&#95;112064205del) in trans with a single nucleotide variant (c.624dup(p.Cys209MetfsTer21)) in CCN6 in a pair of monozygotic twins, through the methods of GS and DP. The twins had received three nondiagnostic results before. The g.112057664&#95;112064205del variant was missed by all the tests, and the recorded phenotypes were inaccurate or even misleading. The twins were diagnosed with PPD, ending a 13-year diagnostic odyssey. There may be other patients with PPD experiencing underdiagnosis and misdiagnosis due to inadequate genetic testing or phenotyping methods. This case highlights the critical role of GS and DP in facilitating an accurate and timely diagnosis., (© 2024 Wiley Periodicals LLC.)

Objectives: The burden of pain in middle-aged and older adults is considerable and significantly increases healthcare expenditures. We aimed to investigate the roles of handgrip strength (HGS) weakness and asymmetry in predicting pain across four nationally representative cohorts., Methods: This longitudinal study utilized data from four major surveys: the Health and Retirement Study (HRS); the English Longitudinal Study of Ageing (ELSA); the Survey of Health, Ageing and Retirement in Europe (SHARE); and the China Health and Retirement Longitudinal Study (CHARLS). Multivariable cubic regression splines were employed to visually explore the nonlinear associations between HGS and pain in each cohort. The Cox proportional hazard model was applied to analyze the independent and combined relationship between HGS weakness and asymmetry and pain risk., Results: We included 41,171 participants in the final analysis, with a mean follow-up period of 4.68 ± 2.61 years (50.7% female, mean age 64.3 ± 9.3 years). No nonlinear relationship was found between HGS and pain incidence (nonlinear p  < 0.05 in ELSA and SHARE; >0.05 in CHARLS and HRS). After adjustment, the highest quartile groups had a significantly reduced risk of pain compared to the lowest quartile groups across all cohorts, with hazard ratios of 0.81 (0.74, 0.89) in CHARLS, 0.86 (0.77, 0.97) in HRS, 0.88 (0.77, 0.98) in ELSA, and 0.78 (0.73, 0.84) in SHARE. Participants with normal HGS had approximately 20% lower risk of pain compared to those with weak HGS. Each 5 kg increase in HGS was associated with decreased hazard ratios for pain: 0.95 (0.93, 0.97) in CHARLS, 0.97 (0.94, 0.99) in HRS, 0.96 (0.94, 0.99) in ELSA, and 0.94 (0.92, 0.95) in SHARE. The association between HGS asymmetry and pain risk was significant only in a few cohorts (HRS at 10%, 1.10 (1.03, 1.18); SHARE at 30%, 1.12 (1.05, 1.21)). No interaction effect between HGS weakness and asymmetry on pain risk was observed (all p -values for interaction >0.05)., Conclusions: Our findings suggest that HGS can be used as an independent predictor of pain in middle-aged and older European, American, and Chinese populations. However, our results do not support the use of HGS asymmetry as an independent predictor of pain risk. It is necessary to establish appropriate criteria for HGS asymmetry across different populations. The use of both weak HGS and asymmetry as predictors of health outcomes requires further validation in more diverse populations., Competing Interests: The authors declare no financial support or other benefits from commercial sources for the work reported on in the manuscript, or any other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work., (© 2024 The Author(s). Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics., (© 2024. The Author(s).)

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC 50 value of 0.13 μM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC 50 , along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan Tongluo Qiangjing recipe (SGTL) on sperm DNA damage and oxidative stress in experimental VC (EVC) rats. EVC model was established by partial ligation of left renal vein. Spermatic vein diameter, testicular weight, sperm DNA fragmentation index (DFI) were evaluated. Telomere reverse transcriptase (TERT) expression, telomere gene transcription, and testicular tissue morphology were determined·H 2 O 2 , catalase, SOD, T-AOC were measured with colorimetry. SGTL significantly decreased spermatic vein diameter (P=0.000) and increased testicular weight (P=0.013) of rats compared those of EVC rats. SGTL maintained testicular tissue morphology in EVC rats. SGTL markedly reduced sperm DFI value in sperm of rats compared to EVC rats (P=0.000). SGTL significantly enhanced TERT expression and telomere gene transcription (P=0.028) in testis of rats compared to EVC rats. SGTL reduced H 2 O 2 levels (P=0.001) and promoted CAT activity (P=0.016), SOD activity (P=0.049), and T-AOC activity (P=0.047) of rats, compared to EVC rats. In conclusion, SGTL could reduce pathogenic process of EVC by reducing sperm DNA damage and regulating telomere length in EVC rats, which may be related to oxidative stress regulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Philadelphia chromosome positive (Ph + ) acute lymphoblastic leukemia (ALL) refers to ALL patients with t(9;22) cytogenetic abnormalities, accounting for about 25% of ALL. Lung adenocarcinoma (LUAD) is the most common pathological type of non-small-cell lung cancer, which has a frequency of approximately 45% cases with mutations in EGFR. Both Ph + ALL and EGFR mutant LUAD are involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway. Although the second primary hematological malignancy after the treatment of solid tumors is common in clinics, the synchronous multiple primary malignant tumors of hematological malignancy overlap solid tumors are uncommon, even both tumors involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway are extremely rare., Case Presentation: An 84-year-old man with fatigue and dizziness was diagnosed with Ph + ALL. Meanwhile, a chest CT indicated a space-occupying lesions, characterized by the presence of void, in the right lower lope with the enlargement of mediastinal lymph node and right pleural effusion. After a few weeks, the patient was diagnosed with LUAD with EGFR exon 19 mutation. Both tyrosine kinase inhibitors (TKI) (Flumatinib) and EGFR-TKI (Oxertinib) was used for the patients, and finally have controlled both diseases., Conclusion: As far as we know, we for the first time reported a case of Ph + ALL and EGFR mutant LUAD synchronous overlap, of which pathogenesis is related to abnormal tyrosine kinase activation. This patient was successfully treated with two different TKIs without serious adverse events., (© 2024. The Author(s).)

Background: Leiomyomas (LMs) are mesenchymal tumors that arise from smooth muscle cells. LMs most commonly arise in organs with an abundance of smooth muscle such as the uterus and gastrointestinal tract. Conversely, LMs are rarely detected in the head and neck region. In this study, we report a rare case of laryngeal LM (LLM) and summarized the clinical characteristics of reported LLMs to help clinicians better understand this rare disease and improve its diagnosis, treatment, and postoperative course., Case Summary: A 49-year-old man was admitted to our ENT outpatient clinic with a chief complaint of pharynx discomfort for 2 months. Laryngoscopy performed under topical anesthesia revealed a solitary, pink mass at the tubercle of epiglottis. Surgery via laryngeal endoscopy was performed under general anesthesia, and the lesion was excised easily. Positive immunohistochemical staining for desmin and smooth-muscle actin indicated a smooth muscle origin and the diagnosis was laryngeal leiomyoma. After surgery, the patient's condition was stable, and he was discharged 2 d after surgery. During the 1-year postoperative period, the patient's condition remained stable without evidence of recurrence., Conclusion: Surgical resection is the preferred treatment for LLMs, its early diagnosis and differential diagnosis have important clinical significance., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Adolescent idiopathic scoliosis (AIS), the predominant genetic-influenced scoliosis, results in spinal deformities without vertebral malformations. However, the molecular aetiology of AIS remains unclear., Methods: Using genome/exome sequencing, we studied 368 patients with severe AIS (Cobb angle >40°) and 3794 controls from a Han Chinese cohort. We performed gene-based and pathway-based weighted rare variant association tests to assess the mutational burden of genes and established biological pathways. Differential expression analysis of muscle tissues from 14 patients with AIS and 15 controls was served for validation., Results: SLC16A8 , a lactate transporter linked to retinal glucose metabolism, was identified as a novel severe AIS-associated gene (p=3.08E-06, false discovery rate=0.009). Most AIS cases with deleterious SLC16A8 variants demonstrated early onset high myopia preceding scoliosis. Pathway-based burden test also revealed a significant enrichment in multiple carbohydrate metabolism pathways, especially galactose metabolism. Patients with deleterious variants in these genes demonstrated a significantly larger spinal curve. Genes related to catabolic processes and nutrient response showed divergent expression between AIS cases and controls, reinforcing our genomic findings., Conclusion: This study uncovers the pivotal role of genetic variants in carbohydrate metabolism in the development of AIS, unveiling new insights into its aetiology and potential treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings., (Copyright © 2024. Published by Elsevier B.V.)

Background: The Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders. EDS is clinically and genetically heterogeneous and usually involves multiple systems. There are 14 subtypes of EDS with hallmark features including joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical manifestations and their severity differ among the subtypes, encompassing recurrent joint dislocations, scoliosis, arterial aneurysm and dissection, and organ rupture. Challenges in diagnosis and management arise from the complexity of the disease, which is further complicated by its rarity. The development of clinical guidelines and implementation of coordinated multi-disciplinary team (MDT) approaches have emerged as global priorities., Main Body: Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes was therefore established. Healthcare professionals were recruited from 25 top hospitals across China. The experts are specialized in 24 fields, including genetics, vascular surgery, dermatology, and orthopedics, as well as nursing care, rehabilitation, psychology, and nutrition. Based on GRADE methodology, the Guidelines were written by the Group supervised by methodologists, following a systemic review of all 4453 articles in PubMed published before August 9, 2023, using the search term "Ehlers Danlos". A coordinated MDT approach for the diagnosis and management of EDS is highly recommended by the Group, along with 29 specific recommendations addressing key clinical questions. In addition to the treatment plan, the Guidelines also emphasize integrating support from nursing care, rehabilitation, psychology, and nutrition. This integration not only facilitates recovery in hospital settings, but most importantly, the transition from an illness-defined life to a more "normalized" life., Conclusion: The first guidelines on EDS will shorten the diagnostic odyssey and solve the unmet medical needs of the patients. This article is a synopsis of the full guidelines., (© 2024. The Author(s).)

Objectives: Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD., Methods: We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship., Results: A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively., Conclusion: Higher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2 , many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder., Competing Interests: Competing interests statement:J.R.L. has stock ownership in 23andMe, is a paid consultant for Regeneron Genetics Center, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical genomic sequencing offered in the Baylor Genetics Laboratory (http://bmgl.com).

The fluorescent flexible sensor for point-of-care quantification of clinical anticoagulant drug, Heparin (Hep), is still an urgent need of breakthrough. In this research, a hyperbranched poly(amido amine) (HPA) was decorated with tetraphenylethene (TPE) and Rhodamine B (RhB), constructing a ratiometric fluorescent sensor (TR-HPA) for Hep. When the sensor was exposed to Hep, the TPE units within the probe skeleton would aggregate, resulting in an increasing fluorescent emission at 483 nm. The 580 nm of fluorescence came from RhB enhance, simultaneously, due to the fluorescence resonance energy transfer. As a result, there are two good linear correlation between the fluorescence emission ratio (E 483 /E 580 ) of TR-HPA and the Hep concentration over a range of 0-1.0 μM, with a low limit of detection of 3.0 nM. Furthermore, we incorporate the TR-HPA probe into a polyvinyl alcohol (PVA) hydrogel matrix to create a flexible fluorescent sensing system platform, denoted as TR-HPA/PVA. This approach offers a straightforward visual detection method by causing a fluorescence color change from pink to blue when trace amounts of Hep are present. The hydrogel-based fluorescent sensor streamlines the detection procedures for Hep in biomedical applications. It shows great potential in rapid and point-of-care human blood clotting condition monitoring, making it suitable for next-generation wearable medical devices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Escherichia coli is one of the important reservoirs of antimicrobial resistance genes (ARG), which often causes food-borne diseases and clinical infections. Contamination with E. coli carrying clinically important antimicrobial resistance genes in retail meat products can be transmitted to humans through the food chain, posing a serious threat to public health. In this study, a total of 330 E. coli strains were isolated from 464 fresh meat samples from 17 food markets in China, two of which were identified as enterotoxigenic and enteropathogenic E. coli. Whole genome sequencing revealed the presence of 146 different sequence types (STs) including 20 new STs, and 315 different clones based on the phylogenetic analysis, indicating the high genetic diversity of E. coli from retail meat products. Antimicrobial resistance profiles showed that 82.42 % E. coli were multidrug-resistant strains. A total of 89 antimicrobial resistance genes were detected and 12 E. coli strains carried clinically important antimicrobial resistance genes bla NDM-1 , bla NDM-5 , mcr-1, mcr-10 and tet(X4), respectively. Nanopore sequencing revealed that these resistance genes are located on different plasmids with the ability of horizontal transfer, and their genetic structure and environment are closely related to plasmids isolated from humans. Importantly, we reported for the first time the presence of plasmid-mediated mcr-10 in E. coli from retail meat. This study revealed the high genetic diversity of food-borne E. coli in retail meat and emphasized their risk of spreading clinically important antimicrobial resistance genes., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

A strictly anaerobic, motile bacterium, designated as strain Ai-910 T , was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C 15 : 0 and anteiso-C 15 : 0 . The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910 T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010 T (92.78%), Alkalitalea saponilacus SC/BZ-SP2 T (92.51%), and Geofilum rubicundum JAM-BA0501 T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910 T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910 T represented a novel species. The average amino acid identity between strain Ai-910 T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910 T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910 T from its close relatives suggest that strain Ai-910 T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910 T (= CGMCC 1.17893 T  = KCTC 25,304 T )., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Two new cassane diterpenoids, sucupiranin MN ( 1 ) and sucupiranin ML ( 2 ), together with two known compounds sucutinirane C ( 3 ) and deacetylsucutinirane C ( 4 ) were isolated from the seed kernels of Caesalpinia sinensis . Their structures were elucidated by means of analysis of comprehensive spectroscopic data, especially HRESIMS and 1D/2D NMR spectroscopy. Compounds 1-4 are typical furan-type cassane derivatives with an aromatized C ring. Biological evaluation revealed that compounds 1-4 at the concentration of 10 μM could inhibit the overproduction of NO in LPS-stimulated RAW 264.7 macrophages.

Leveraging protein structural information to evaluate pathogenicity has been hindered by the scarcity of experimentally determined 3D protein. With the aid of AlphaFold2 predictions, we developed the structure-informed genetic missense mutation assessor (SIGMA) to predict missense variant pathogenicity. In comparison with existing predictors across labeled variant datasets and experimental datasets, SIGMA demonstrates superior performance in predicting missense variant pathogenicity (AUC = 0.933). We found that the relative solvent accessibility of the mutated residue contributed greatly to the predictive ability of SIGMA. We further explored combining SIGMA with other top-tier predictors to create SIGMA+, proving highly effective for variant pathogenicity prediction (AUC = 0.966). To facilitate the application of SIGMA, we pre-computed SIGMA scores for over 48 million possible missense variants across 3,454 disease-associated genes and developed an interactive online platform (https://www.sigma-pred.org/). Overall, by leveraging protein structure information, SIGMA offers an accurate structure-based approach to evaluating the pathogenicity of missense variants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Corynoxeine, a natural active alkaloid found in Genus Uncaria, has been reported to have anti-depressant effects. In this study, a sensitive and efficient ultra-high performance liquid chromatography tandem mass spectrometry method for quantifying corynoxeine in rat plasma and tissues was established, validated and applied to investigate the pharmacokinetics and tissue distribution differences between normal rats and chronic unpredictable mild stress (CUMS)-induced depression model rats following oral administration. All bio-samples were prepared by methanol protein precipitation method with theophylline as internal standard (IS). Chromatographic separation was conducted on an Agilent ZORBAX Eclipse Plus C18 column using mobile phase A (acetonitrile) and B (0.1% formic acid in water) in gradient elution mode with a flow rate of 0.3 mL/min. Mass spectrometric detection was performed in multiple-reaction monitoring mode with positive electrospray ionization source. The transitions of m/z 383.0→160.2 for corynoxeine and m/z 181.1→124.0 for IS were chosen for quantification. The method showed good linearity, stability, accuracy, precision, recovery, and non-significant matrix effect, which were within the acceptable ranges. The pharmacokinetic results revealed that the absorption and bioavailability of corynoxeine in depression rats decreased compared to normal rats. The tissue distribution of corynoxeine trended to be mostly in the intestine and stomach and the distribution of this compound in intestine tissue of depression rats was significantly increased compared to the normal rats. The pharmacokinetics and tissue distribution profiles of corynoxeine were altered in CUMS-induced depression rats compared to normal rats and these experimental findings could provide beneficial information to the mechanism research and clinical applications of corynoxeine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)