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Yanan Shi,1,2,* Wan Huang,1,* Rongcai Liang,1–3 Kaoxiang Sun,2,3 Fangxi Zhang,2,3 Wanhui Liu,2,3 Youxin Li1–31College of Life Science, Jilin University, Changchun, China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co, Ltd, Yantai, China; 3School of Pharmacy, Yantai University, Yantai, China*These authors contributed equally to this workAbstract: To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO), rhEPO was successfully formulated into poly(ethylene glycol)–poly(d,l-lactide) (PEG–PLA) di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI < 0.3) and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of −3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG–PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG–PLA micelles can be a potential protein drug delivery system.Keywords: rhEPO, PEG–PLA micelle, in vitro, pharmacokinetics, pharmacodynamics

Climate change can exacerbate pest population growth, posing significant threats to ecosystem functions and services, social development, and food security. Risk assessment is a valuable tool for effective pest management that identifies potential pest expansion and ecosystem dispersal patterns. We applied a habitat suitability model coupled with priority protection planning software to determine key monitoring areas (KMA) for tree insect pest risks under climate change and used forest ecoregions and nature reserves to assess the ecological risk of insect pest invasion. Finally, we collated the prevention and control measures for reducing future pest invasions. The KMA for tree insect pests in our current and future climate is mainly concentrated in eastern and southern China. However, with climate change, the KMA gradually expands from southeastern to northeastern China. In the current and future climate scenarios, ecoregions requiring high monitoring levels were restricted to the eastern and southern coastal areas of China, and nature reserves requiring the highest monitoring levels were mainly distributed in southeastern China. Tree insect pest invasion assessment using ecoregions and nature reserves identified that future climates increase the risk of pest invasions in forest ecoregions and nature reserves, especially in northeastern China. The increased risk and severity of tree insect pest invasions require implementing monitoring and preventative measures in these areas. We effectively assessed the pest invasion risks using forest ecoregions and nature reserves under climate change. Our assessments suggest that monitoring and early prevention should focus on southeastern and northeastern China., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Rationale: Isopsoralen (ISO), a quality control marker (Q-marker) in Psoraleae Fructus, is proven to present an obvious anti-osteoporosis effect. Until now, the metabolism and anti-osteoporosis mechanisms of ISO have not been fully elucidated, greatly restricting its drug development., Methods: The metabolites of ISO in rats were profiled by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-osteoporosis mechanism of ISO in vivo was predicted by using network pharmacology., Results: A total of 15 metabolites were characterized in rats after ingestion of ISO (20 mg/kg/day, by gavage), including 2 in plasma, 12 in urine, 6 in feces, 1 in heart, 3 in liver, 1 in spleen, 1 in lung, 3 in kidney, and 2 in brain. The pharmacology network results showed that ISO and its metabolites could regulate AKT1, SRC, NFKB1, EGFR, MAPK3, etc., involved in the prolactin signaling pathway, ErbB signaling pathway, thyroid hormone pathway, and PI3K-Akt signaling pathway., Conclusions: This is the first time for revealing the in vivo metabolism features and potential anti-osteoporosis mechanism of ISO by metabolite profiling and network pharmacology, providing data for further verification of pharmacological mechanism., (© 2024 John Wiley & Sons Ltd.)

Rationale: Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti-osteoporotic mechanism are still unclear, restricting its development and application., Methods: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti-osteoporosis targets and mechanism were predicted using network pharmacology., Results: A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan-ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K-Akt signaling pathway, estrogen signaling pathway, and so on., Conclusions: This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti-osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis., (© 2024 John Wiley & Sons Ltd.)

Background: Depersonalization-Derealization Disorder (DPD), a prevalent psychiatric disorder, fundamentally disrupts self-consciousness and could significantly impact the quality of life of those affected. While existing research has provided foundational insights for this disorder, the limited exploration of brain dynamics in DPD hinders a deeper understanding of its mechanisms. It restricts the advancement of diagnosis and treatment strategies. To address this, our study aimed to explore the brain dynamics of DPD., Methods: In our study, we recruited 84 right-handed DPD patients and 67 healthy controls (HCs), assessing them using the Cambridge Depersonalization Scale and a subliminal self-face recognition task. We also conducted a Transcranial Direct Current Stimulation (tDCS) intervention to understand its effect on brain dynamics, evidenced by Functional Magnetic Resonance Imaging (fMRI) scans. Our data preprocessing and analysis employed techniques such as Independent Component Analysis (ICA) and Dynamic Functional Network Connectivity (dFNC) to establish a comprehensive disease atlas for DPD. We compared the brain's dynamic states between DPDs and HCs using ANACOVA tests, assessed correlations with patient experiences and symptomatology through Spearman correlation analysis, and examined the tDCS effect via paired t-tests., Results: We identified distinct brain networks corresponding to the Frontoparietal Network (FPN), the Sensorimotor Network (SMN), and the Default Mode Network (DMN) in DPD using group Independent Component Analysis (ICA). Additionally, we discovered four distinct dFNC states, with State-1 displaying significant differences between DPD and HC groups (F = 4.10, P = 0.045). Correlation analysis revealed negative associations between the dwell time of State-2 and various clinical assessment factors. Post-tDCS analysis showed a significant change in the mean dwell time for State-2 in responders (t-statistic = 4.506, P = 0.046), consistent with previous clinical assessments., Conclusions: Our study suggests the brain dynamics of DPD could be a potential biomarker for diagnosis and symptom analysis, which potentially leads to more personalized and effective treatment strategies for DPD patients., Trial Registrations: The trial was registered at the Chinese Clinical Trial Registry on 03/01/2021 (Registration number: ChiCTR2100041741, https://www.chictr.org.cn/showproj.html?proj=66731 ) before the trial., (© 2024. The Author(s).)

The invasion of alien woody species may have broad ecological, economic, and health impacts on ecosystems and biodiversity under climate change. Previous studies showed that disrupting the biodiversity conservation mechanisms in protected areas can seriously threaten natural ecosystems and the protection of rare and endangered species in such protected areas. However, there is currently no standard for evaluating the invasion risk of woody plants under climate change when establishing national parks in China. Therefore, we used a species distribution model to evaluate the invasion risk of 250 invasive alien woody species in potential national park sites in Xinjiang under climate change. The results indicated that the probability of forest invasion in the potential Altai Kanas National Park was determined to be significantly higher than that of the average level in Xinjiang nature reserves, both under current and future climate conditions. At the same time, the probability of invasive woody species invading coniferous forests, broad-leaved forests, and grassland ecosystems is higher in the Altai Kanas and Tianshan potential national parks. We found that Acer negundo , Robinia pseudoacacia , and Amorpha fruticose in potential parks in Xinjiang have higher invasion potential and thus require heightened vigilance to stop their spread. This study contributes to the monitoring and management of national parks and provides an actionable foundation for protecting ecosystem functions and minimizing the potential risk of invasive alien species under climate change., Competing Interests: The authors declare no conflicts of interest, and the manuscript was approved by all authors for publication., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Health professional education stands to gain substantially from collective efforts toward building video databases of skill performances in both real and simulated settings. An accessible resource of videos that demonstrate an array of performances - both good and bad-provides an opportunity for interdisciplinary research collaborations that can advance our understanding of movement that reflects technical expertise, support educational tool development, and facilitate assessment practices. In this paper we raise important ethical and legal considerations when building and sharing health professions education data. Collective data sharing may produce new knowledge and tools to support healthcare professional education. We demonstrate the utility of a data-sharing culture by providing and leveraging a database of cardio-pulmonary resuscitation (CPR) performances that vary in quality. The CPR skills performance database (collected for the purpose of this research, hosted at UK Data Service's ReShare Repository) contains videos from 40 participants recorded from 6 different angles, allowing for 3D reconstruction for movement analysis. The video footage is accompanied by quality ratings from 2 experts, participants' self-reported confidence and frequency of performing CPR, and the demographics of the participants. From this data, we present an Automatic Clinical Assessment tool for Basic Life Support that uses pose estimation to determine the spatial location of the participant's movements during CPR and a deep learning network that assesses the performance quality., (© 2024. Crown.)

Ethnopharmacological Relevance: Zanthoxyli Radix (ZR), the dry root of Zanthoxylum nitidum (Roxb.) DC (ZN) is known as Liang Mian Zhen in China and has been the preferred Chinese medicine for the treatment of inflammation and cancer disease at home and abroad. ZR has been used as the core ingredient in anti-inflammatory traditional medicines, such as Sanjiuweitai granules and Jinji tablets, etc. AIM OF THE WORK: This review aimed to provide a comprehensive overview of ZR in terms of traditional uses, quality control, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics. Meanwhile, the anti-inflammatory substances and mechanism of ZR were emphasized, to offer new perspectives and broad scopes for future studies., Materials and Methods: The information was retrieved from Web of Science, Researchgate, Google Scholar, SciFinder, X-MOL, PubMed, China National Knowledge Infrastructure (CNKI), Chinese Masters and Doctoral Dissertations, and Elsevier between 1984 and 2024., Results: Till now, a total of 184 chemical components have been identified in ZR, including 91 alkaloids, 22 lignans, 4 flavonoids, 19 coumarins, 17 terpenoids, and 31 other types. Pharmacological studies have proved that ZR had a variety of biological activities, such as anti-tumour, antibacterial, antioxidant and other activities, particularly in anti-inflammation. ZR exerts anti-inflammatory disease effects by modulating various signaling pathways, including MAPK, NF-κB, P13/AKT and JAK/STAT. Pharmacokinetic studies have shown that ZR exhibits low absorption rates, broad distribution, and rapid metabolism. Additionally, this review also revealed the shortcomings of current research on ZR and possible future research directions., Conclusion: Extensive literature analysis indicates that ZR and its bioactive constituents possess diverse pharmacological activities, especially anti-inflammation. Moreover, in order to promote the safety and adaptability of ZR in clinical application, it is also strongly recommended that further research should focus on toxicity studies, pharmacokinetic studies of herb-drug interactions, and quality control., 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.)

Ethnopharmacological Relevance: Sophorae tonkinensis Radix et Rhizoma (STR), the dried root and rhizome of Sophora tonkinensis Gagnep., is commonly used in the treatment of tonsillitis and pharyngitis, throat soreness and throat obstruction, swelling and aching of gum, etc. in China or other Asian countries. STR is usually used as the core herb in traditional Chinese medicine preparations, such as "Biyanling Tablets", "Fufang Muji Granules" and "Ganyanling Injections", etc. AIM OF THE REVIEW: This review aimed to provide a comprehensive analysis of STR in terms of botany, traditional use, phytochemistry, ethnopharmacology, pharmacology, pharmacokinetics, toxicology and detoxification strategy, to provide a rational application in future research., Materials and Methods: The information involved in the study was gathered from a variety of electronic resources, including China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations., Results: Till now, a total of 333 chemical components have been identified in STR, including 85 alkaloids, 124 flavonoids, 24 triterpenes, 27 triterpene saponins, 34 organic acids, 8 polysaccharides, etc. STR and its main active constituents have cardiovascular protection, anti-tumor activity, anti-inflammatory activity, antipyretic activity, analgesic activity, antibacterial activity, antifungal activity, antiviral activity, and hepatoprotective activity, etc. However, toxic effects of STR on the liver, nerves, heart, and gastrointestinal tract have also been observed. To mitigate these risks, STR needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. The pharmacokinetics of STR in vivo and traditional and clinical prescriptions containing STR have been sorted out. Despite the potential therapeutic benefits of STR, further research is warranted to elucidate its hepatotoxicity, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and mechanisms., Conclusion: This review serves to emphasize the therapeutic potential of STR and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the toxicological properties of STR, with particular emphasis on its hepatotoxicity and neurotoxicity. Such research endeavors have the potential to standardize the rational application of STR for optimal therapeutic outcomes., 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.)

Owing to its ability to separate substances with a broad scope of polarities, exploring the three-phase solvent systems (TPSSs) with high-speed countercurrent chromatography is a topic of interest in separation science, and their retention volumes should be more concerned. This study primarily investigates the behavior of retention volumes while examining the isolation abilities of the TPSS in the technique above. We took standard compounds, including sophoricoside, Sudan red 7B, and rotenone, which have a broad range of polarity, for investigation in this study and separated them using different four-liquid TPSSs made up of water, acetonitrile, methyl acetate, and n-hexane (WAMH). Our findings show that the retention volumes gradually alter in response to changes in phase polarity within the proposed solvent systems. With TPSSs, we preliminarily studied compound isolation and the promising formula of their retention volumes. The proposed solvent systems WAMH in different ratios showed high correlations and adjusted correlation coefficients above 0.9978 and 0.9913 for the actual and calculated retention volumes. This study will be particularly beneficial for researchers focusing on countercurrent chromatography with TPSSs, as it offers valuable time-saving insights., (© 2024 Wiley‐VCH GmbH.)

Zhi-Ke-Bao pills (ZKB), a traditional Chinese medicine preparation composed of 13 herbs, is generally used to treat cough caused by external wind cold, phlegm, etc in clinical applications, and it plays a core role in relieving cough caused by COVID-19 and influenza in China. Till now, the understanding of its chemical constituents was dramatically limited due to its chemical complexity, restricting its clinical application or development. In this work, a developed ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) method, a targeted and non-targeted strategy and network pharmacology were used to comprehensively characterize the chemical compositions in ZKB and predict its mechanism against cough. A total of 164 compounds (148 targeted compounds and 16 non-targeted ones) were identified or tentatively characterized in ZKB, including 65 flavonoids, 25 alkaloids, 19 organic acids, 41 saponins, 9 coumarins, 2 phenylpropanoids, 2 anthraquinones, and 1 other types. Among them, 37 compounds were unambiguously identified by comparison to reference standards. Meanwhile, the fragmentation behaviors of five main chemical structure types were also summarized. 309 targets and two core signaling pathways of ZKB against cough were predicted by network pharmacology, including MAPK and PI3K-Akt signaling pathways. It was the first time to characterize the chemical compounds of ZKB and reveal its potential mechanism against cough, providing the material basis for further quality control or pharmacodynamic evaluation of ZKB., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Feng-Xiang Zhang reports financial support was provided by Teyi Pharmaceutical Group Co., Ltd. Qing-Min Zhang reports a relationship with Teyi Pharmaceutical Group Co., Ltd that includes: employment. If there are other authors, they 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. Published by Elsevier B.V.)

Aim: To compare the dosimetric advantages and disadvantages between hybrid intensity-modulated radiation therapy (h-IMRT) and the volumetric modulated arc therapy (VMAT) technique in hypofractionated whole-breast irradiation (HF-WBI) for early-stage breast cancer (BC)., Methods: The dose distribution of h-IMRT and VMAT plans was compared in 20 breast cancer patients. This comparison included evaluation of dosimetric parameters using dose volume histograms (DVHs) for the planning target volume (PTV) and organs-at-risk (OARs). Additionally, the study examined the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) and the tumor control probability (TCP) based on different models., Results: Significant differences were detected between the two plans, in terms of Machine units (MUs), the control points, 95 % volume (V95 %), dose homogeneity index (DHI) and conformity index (CI). The endpoint of grade II radiation pneumonitis and cardiac death due to ischemic heart disease were assessed. In h-IMRT plan, the NTCP values were marginally lower for radiation pneumonitis and slightly higher for cardiac death compared to VMAT plan, as determined by the Lyman-Kutcher-Burman model. The Schneider model was employed to predict the SCCP for both the bilateral lungs and contralateral breast, the results demonstrate that the h-IMRT plan outperforms the VMAT plan, with statistical significance. Additionally, the LQ-Poisson model was employed to forecast the TCP of the PTV, showing that the h-IMRT plan outperformed the VMAT plan (P > 0.05)., Conclusion: The h-IMRT technique, offering superior dose coverage and better therapeutic efficacy with fewer side effects as calculated by models, is more suitable for HF-WBI compared to the VMAT technique., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Ethnopharmacological Relevance: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects., Aim of the Study: To understand the material foundation and liver injury mechanism of STR., Materials and Methods: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot., Results: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment., Conclusions: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI., 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.)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Background: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate., Methods: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery., Results: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups., Conclusions: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA., Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578)., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: The self-repair ability after meniscal tears is poor, leading to the development of posttraumatic osteoarthritis. Promoting the repair of meniscal injuries remains a great challenge, especially in the avascular region., Hypothesis: Local delivery of skeletal stem cell (SSC)-derived exosomes (SSC-Exos) would promote meniscal healing and prevent secondary osteoarthritis progression., Study Design: Controlled laboratory study., Methods: SSCs were isolated from bone marrow and exosomes were extracted via ultracentrifugation. The cell migration capabilities after incubation with exosomes were validated through in vitro cell culture. Full-thickness longitudinal medial meniscal tears were performed in the avascular region of 40 male Sprague-Dawley rats and 20 male New Zealand White rabbits, which were randomly divided into 2 groups: group treated with phosphate-buffered saline (G CON ) and group treated with exosomes (G Exosome ). The effects of these treatments on meniscal healing and secondary osteoarthritis were evaluated by gross inspection, biomechanical testing, and histological assessment. RNA sequencing of in vitro cell cultures was performed to explore the underlying mechanisms., Results: Exosomes were successfully extracted and identified. These exosomes significantly promoted cell migration capabilities in vitro ( P < .01). The G Exosome exhibited greater cell proliferation and tissue regeneration with type 2 collagen secretion, and a significantly higher meniscal repair score than that of the G CON at 8 weeks postoperatively ( P < .05). In contrast to the degenerative changes in both the meniscus and articular cartilage of the G CON , meniscal tissue in the G Exosome exhibited restoration of normal morphology with a smooth and glossy white surface and better mechanical strength at 8 weeks after meniscal repair. Both degeneration scores and synovitis scores were significantly higher in the G CON than in the G Exosome ( P < .05). Compared with the G CON , the expression of key genes related to cell migration, such as the chemokine family, was enhanced by exosome injection, leading to an upregulation of extracellular matrix expression while downregulating the expression of inflammation-related genes such as CD68 and the matrix metalloproteinase family., Conclusion: The administration of SSC-Exos effectively promoted meniscal healing in the avascular region and ameliorated secondary osteoarthritis. The effect might be attributed to inflammation modulation, promotion of cell migration, and secretion of extracellular matrix components., Clinical Relevance: Injection of SSC-Exos represents a promising therapeutic option for promoting meniscal healing in the avascular region., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by National Natural Science Foundation of China (No. 82072428, No. 823B2057) and Natural Science Foundation of Beijing, China (No. 7212132). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Several prospective studies have found that local surgical resection did not improve the survival of patients with de novo metastatic breast cancer (dnMBC). However, a significant portion of dnMBC patients still undergo local surgery, and the role of axillary lymph node dissection (ALND) in dnMBC patients remains unclear. This study aimed to investigate the effect of ALND in patients with dnMBC., Methods: We included patients diagnosed with dnMBC between 2010 and 2020 using the data from the Surveillance, Epidemiology, and End Results program. The Chi-square test, binomial logistic regression, propensity score matching (PSM), Kaplan-Meier method, and multivariate Cox proportional models were employed for statistical analysis., Results: A total of 6,838 patients were identified, with 5,562 (81.3%) in the ALND group and 1,276 (18.7%) in the non-ALND group. Being diagnosed in later years emerged as an independent predictive factor related to the receipt of ALND (P=0.003). Before PSM, the 5-year breast cancer-specific survival (BCSS) was 51.1% and 38.2% in those with and without ALND, respectively (P<0.001). The 5-year overall survival (OS) was 45.9% and 32.3% in those with and without ALND, respectively (P<0.001). ALND was identified as an independent prognostic factor related to better BCSS (P<0.001) and OS (P<0.001) compared to the non-ALND group. Similar findings were observed after PSM. The outcomes were significantly better in the ALND group than in the non-ALND group in most subgroups. However, the number of removed lymph nodes did not show a significant association with BCSS (P=0.27) and OS (P=0.29)., Conclusions: Our study suggests that ALND is associated with improved survival outcomes in dnMBC patients. These findings advocate for a re-evaluation of the role of surgical interventions in dnMBC, emphasizing the need for personalized treatment strategies that consider the potential benefits of ALND., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-130/coif). The authors have no conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Converting CO 2 into value-added products containing B-C bonds is a great challenge, especially for multiple B-C bonds, which are versatile building blocks for organoborane chemistry. In the condensed phase, the B-C bond is typically formed through transition metal-catalyzed direct borylation of hydrocarbons via C-H bond activation or transition metal-catalyzed insertion of carbenes into B-H bonds. However, excessive amounts of powerful boryl reagents are required, and products containing B-C bonds are complex. Herein, a novel method to construct multiple B-C bonds at room temperature is proposed by the gas-phase reactions of CO 2 with LaB m O n - ( m = 1-4, n = 1 or 2). Mass spectrometry and density functional theory calculations are applied to investigate these reactions, and a series of new compounds, CB 2 O 2 - , CB 3 O 3 - , and CB 3 O 2 - , which possess B-C bonds, are generated in the reactions of LaB 3,4 O 2 - with CO 2 . When the number of B atoms in the clusters is reduced to 2 or 1, there is only CO-releasing channel, and no CB x O y - compounds are released. Two major factors are responsible for this quite intriguing reactivity: (1) Synergy of electron transfer and boron-boron Lewis acid-base pair mechanisms facilitates the rupture of C═O double bond in CO 2 . (2) The boron sites in the clusters can efficiently capture the newly formed CO units in the course of reactions, favoring the formation of B-C bonds. This finding may provide fundamental insights into the CO 2 transformation driven by clusters containing lanthanide atoms and how to efficiently build B-C bonds under room temperature.

This study examines research perspective in the clinical diagnosis, treatment, and prevention of cardiovascular complications in Kawasaki Disease (KD). Starting with an overview of the disease, it introduces KD's clinical manifestations, etiology, epidemiological features, and its impact on the cardiovascular system. Subsequently, the study discusses in detail the diagnostic methods, pathological mechanisms, and treatment strategies for KD, including foundational and emerging approaches such as high-dose intravenous immunoglobulin and aspirin therapy, biologic therapy, and corticosteroid pulse therapy. Additionally, it outlines strategies for preventing cardiovascular complications, including early risk assessment and long-term management. The study also explores the intersection of the COVID-19 pandemic with an increase in KD-like symptoms, emphasizing the need for further studies on the association between SARS-CoV-2 and KD. Lastly, it explores future research directions to enhance understanding of KD and improve patient outcomes and quality of life. This study provides valuable insights into the comprehensive treatment and management of KD and highlights avenues for future research., 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., (© 2024 Yi, Zhang, Wang, Wang and Zhang.)

Background: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes., Methods and Results: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets., Conclusions: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals., (© 2024. The Author(s).)

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications., 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.)

Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids. The pharmacological activities of AH extracts and their pure compounds have been explored in the aspects of anti-hyperlipidaemia, hepatoprotection, anti-tumour, anti-viral, anti-bacterial, anti-inflammatory and analgesic, immunomodulation, antioxidant and others. The pharmacokinetics and excretion kinetics of AH in vivo and 15 traditional and clinical prescriptions containing AH have been sorted out, and the potential therapeutic mechanism and drug metabolism pattern were also summarised. The pods of ACH are toxic, with a median lethal dose (LD 50 ) of 10.01 ± 2.90 g/kg (i.g.) in mice. Interestingly, the toxicity of ACH's pods and seeds decreased after boiling. However, the toxicity mechanism of pods of ACH is unclear, limiting its clinical application. Clinical trials in the future should be used to explore its safety. Meanwhile, as one of the relevant pharmacological activities, the effects and mechanism of AH on anti-hyperlipidaemia and hepatoprotection should be further studied, which is of great significance for understanding its mechanism of action in the treatment of NAFL disease and improving its clinical application., 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.)

Purpose: Current methods for diagnosis of PD rely on clinical examination. The accuracy of diagnosis ranges between 73 and 84%, and is influenced by the experience of the clinical assessor. Hence, an automatic, effective and interpretable supporting system for PD symptom identification would support clinicians in making more robust PD diagnostic decisions., Methods: We propose to analyze Parkinson's tremor (PT) to support the analysis of PD, since PT is one of the most typical symptoms of PD with broad generalizability. To realize the idea, we present SPA-PTA, a deep learning-based PT classification and severity estimation system that takes consumer-grade videos of front-facing humans as input. The core of the system is a novel attention module with a lightweight pyramidal channel-squeezing-fusion architecture that effectively extracts relevant PT information and filters noise. It enhances modeling performance while improving system interpretability., Results: We validate our system via individual-based leave-one-out cross-validation on two tasks: the PT classification task and the tremor severity rating estimation task. Our system presents a 91.3% accuracy and 80.0% F1-score in classifying PT with non-PT class, while providing a 76.4% accuracy and 76.7% F1-score in more complex multiclass tremor rating classification task., Conclusion: Our system offers a cost-effective PT classification and tremor severity estimation results as warning signs of PD for undiagnosed patients with PT symptoms. In addition, it provides a potential solution for supporting PD diagnosis in regions with limited clinical resources., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) were once used as the same herb in China, but they were distinguished by Chinese Pharmacopoeia in 2005 in terms of their medicinal history, plant morphology, medicinal properties and chemical constituents. However, their functions, flavor, and meridian tropism are the same according to the Chinese pharmacopoeia 2020 edition, making researchers and customers confused., Aim of the Review: This review aimed to provide a comparative analysis of LJF and LF in order to provide a rational application in future research., Materials and Methods: The information was gathered from China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations (all chosen articles were reviewed attentively from 1980.1 to 2023.8)., Results: Till now, 507 chemical compounds have been isolated and identified in LJF, while 223 ones (79 overlapped compounds) are found in LF, including organic acids and derivatives, flavonoids, triterpenoids, iridoids, and essential oil components, etc. In addition, the pharmacological activities of LJF and LF, especially for their anti-influenza efficacy and mechanism, and their difference in terms of pharmacokinetic parameters, toxicology, and clinical applications were also summarized., Conclusion: The current work offers comparative information between LJF and LF in terms of botany, traditional uses, phytochemistry, ethnopharmacology, pharmacokinetics, toxicology, and pharmacology, especially their anti-influenza activities. Despite the same clinical applications and similar chemical components in LJF and LF, differentiated components were still existed, resulting in differentiated pharmacological activities and pharmacokinetics parameters. Moreover, the research about anti-influenza mechanism and functional substances of LJF and LF is dramatically limited, restricting their clinical applications. In addition, few studies have investigated the metabolism feature of LF in vivo, which is one of the important bases for revealing the pharmacological mechanism of LF. At the same time, the toxicity of LJF and LF is not fully studied, and the toxic compounds of LJF and LF need to be screened out in order to standardize the drug use and improve their rational applications., Competing Interests: Declaration of competing interest The author declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Background: In those with one to three positive lymph nodes (N1) breast cancer (BC), the 21-gene recurrence score (RS) classification can be referred for decision-making on adjuvant chemotherapy. This study aimed to investigate the effect of RS in predicting the survival benefit of postoperative radiotherapy (PORT) in T1-2N1 BC with estrogen receptor-positive and human epidermal growth factor receptor 2-negative disease after breast-conserving surgery (BCS)., Methods: We included patients with BC and available RS data from the Surveillance, Epidemiology, and End Results Oncotype DX database. The chi-square test, Kaplan-Meier method, propensity score matching (PSM) as well as multivariable Cox proportional hazard analyses were used for statistical analyses., Results: We included 6509 patients in the analysis. Of these patients, 5302 (85.5%) were treated with BCS + PORT, and 207 (15.5%) had BCS alone. There were 1419 (21.8%), 4319 (66.4%), and 771 (11.8%) patients being low-, intermediate-, and high-risk RS, respectively. After PSM, PORT was significantly associated with a 5-year overall survival (OS) advantage (95.1% vs. 90.5%, P < 0.001) compared to those without PORT, which similar breast cancer-specific survival (BCSS) was found between the treatment arms (P = 0.126). The sensitivity analyses showed that PORT was not associated with a better BCSS (P = 0.472) and OS (P = 0.650) than those without PORT in the low-risk RS cohort. However, PORT was associated with a better BCSS (P = 0.031) and OS (P < 0.001) compared to those without PORT in the intermediate/high-risk RS cohorts., Conclusions: Our study highlights the possible role of the RS in predicting the outcome of PORT in T1-2N1 luminal BC patients undergoing BCS., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Appendage regeneration relies on the formation of blastema, a heterogeneous cellular structure formed at the injury site. However, little is known about the early injury-activated signaling pathways that trigger blastema formation during appendage regeneration. Here, we provide compelling evidence that the extracellular signal-regulated kinase (ERK)-activated casein kinase 2 (CK-2), which has not been previously implicated in appendage regeneration, triggers blastema formation during leg regeneration in the American cockroach, Periplaneta americana . After amputation, CK-2 undergoes rapid activation through ERK-induced phosphorylation within blastema cells. RNAi knockdown of CK-2 severely impairs blastema formation by repressing cell proliferation through down-regulating mitosis-related genes. Evolutionarily, the regenerative role of CK-2 is conserved in zebrafish caudal fin regeneration via promoting blastema cell proliferation. Together, we find and demonstrate that the ERK-activated CK-2 triggers blastema formation in both cockroach and zebrafish, helping explore initiation factors during appendage regeneration.

Countercurrent chromatography (CCC) is a potent separation approach known for its remarkable efficiency and capacity in preparation. It's applied as a substitute or combined with different chromatographic techniques, resulting in its rebranding as multidimensional CCC (MDCCC). Numerous essential mixtures from natural products contain hundreds or thousands of distinct components of importance. These mix types are too complicated to separate in any reasonable time using a single CCC dimension. However, if a multidimensional technique is utilized, where a complex mixture is separated by an initial dimension, smaller fractions of that separation are gathered. Each fraction is studied individually; complex mixes can be resolved relatively quickly. Thus, several MDCCC separation features have been studied to demonstrate their advantages, limitations, and prospective capacity to separate exceedingly complex mixtures. In this review, MDCCC aspects, including principles, multiple columns system, multilayer coil J-type, on-line monitoring system, and applications, have been thoroughly&#95;explored., (© 2024 Wiley-VCH GmbH.)

N 2 adsorption is a prerequisite for activation and transformation. Time-of-flight mass spectrometry experiments show that the Nb 2 C 6 H 4 + cation, resulting from the gas-phase reaction of Nb 2 + with C 6 H 6 , is more favorable for N 2 adsorption than Nb + and Nb 2 + cations. Density functional theory calculations reveal the effect of the ortho -C 6 H 4 ligand on N 2 adsorption. In Nb 2 C 6 H 4 + , interactions between the Nb-4d and C-2p orbitals enable the Nb 2 + cation to form coordination bonds with the ortho -C 6 H 4 ligand. Although the ortho -C 6 H 4 ligand in Nb 2 C 6 H 4 + is not directly involved in the reaction, its presence increases the polarity of the cluster and brings the highest occupied molecular orbital (HOMO) closer to the lowest occupied molecular orbital (LUMO) of N 2 , thereby increasing the N 2 adsorption energy, which effectively facilitates N 2 adsorption and activation. This study provides fundamental insights into the mechanisms of N 2 adsorption in "transition metal-organic ligand" systems.

Objective: To investigate the effects of exosome derived from miR-133a-3p engineered human umbilical cord blood mesenchymal stem cells (ucMSC) on myocardial repair after acute myocardial infarction (AMI) in rats. Methods: UcMSC was amplified and cultured in vitro . Lentiviral carrying miR-133a-3p and negative control vectors were transfected into ucMSC. Exosomes secreted by the transfected ucMSC were named miR-133a-3p-Exo and miR-NC-Exo, respectively. The AMI model of rats was established by ligation of the left anterior descending coronary artery. MiR-133a-3p-Exo or miR-NC-Exo were then injected into the border zone of the infarct area. Cardiac function was assessed by echocardiography after twenty-eight days of intervention, and Masson staining was used to evaluate the area of myocardial fibrosis post-AMI. The myocardial apoptosis after infarction was evaluated by TUNEL staining and the angiogenesis after infarction was evaluated by immunofluorescence staining in the current study. Results: Compared with the miR-NC-Exo group, the left ventricular ejection fraction in the miR-133a-3p-Exo group was significantly increased ((47.4%±9.8%) vs. (64.2%±8.9%), P <0.05). While the myocardial fibrosis area ((31.2%±7.3%) vs. (18.0%±1.5%), P <0.01) and the percentage of apoptotic cardiomyocytes ((25.6%±3.6%) vs. (15.1%±4.4%), P <0.05) was significantly reduced in the miR-133a-Exo group. Besides, the expression of CD31 and α-smooth muscle actin (α-SMA) were also increased significantly in the miR-133a-3p-Exo group compared to the miR-NC-Exo group (CD31: (2.9±0.9) vs. (13.9±2.0), P <0.000 1, α-SMA: (3.5±0.9) vs. (11.0±1.6), P <0.000 1). Conclusion: Exosome derived from miR-133a-3p engineered ucMSC effectively inhibited myocardial apoptosis and promoted angiogenesis, thus improving the cardiac function after myocardial infarction in rats.

The cleavage of inert C-H bonds in methane at room temperature and the subsequent conversion into value-added products are quite challenging. Herein, the reactivity of boron-doped cobalt oxide cluster cations CoBO 2 + toward methane under thermal collision conditions was studied by mass spectrometry experiments and quantum-chemical calculations. In this reaction, one H atom and the CH 3 unit of methane were transformed separately to generate the product metaboric acid (HBO 2 ) and one CoCH 3 + ion, respectively. Theoretical calculations strongly suggest that a catalytic cycle can be completed by the recovery of CoBO 2 + through the reaction of CoCH 3 + with sodium perborate (NaBO 3 ), and this reaction generates sodium methoxide (CH 3 ONa) as the other value-added product. This study shows that boron-doped cobalt oxide species are highly reactive to facilitate thermal methane transformation and may open a way to develop more effective approaches for methane (CH 4 ) activation and conversion under mild conditions.

Nitrogen (N 2 ) activation at room temperature has long been a great challenge. Therefore, the rational design of reactive species to adsorb N 2 , which is a prerequisite for cleavage of the strong N≡N triple bond in industrial and biological processes, is highly desirable and meaningful. Herein, the N 2 adsorption process is controlled by regulating the types and numbers of organic ligands, and the organic ligands are produced through the reactions of Ir + with methane and ethane. CH 4 molecules dissociate on the Ir + cations to form Ir(CH 2 ) 1,2 + . The reaction of Ir + with C 2 H 6 can generate HIrC 2 H 3 + , which is different from the structure of Ir(CH 2 ) 2 + obtained from Ir + /CH 4 . The reactivity order of N 2 adsorption is Ir(CH 2 ) 2 + > HIrC 2 H 3 + ≫ HIrCH + ≈ Ir + (almost inert under similar reaction conditions), indicating that different organic ligand structures affect reactivity dramatically. The main reason for this interesting reactivity difference is that the lowest unoccupied molecular orbital (LUMO) level of Ir(CH 2 ) 2 + is much closer to the highest occupied molecular orbital (HOMO) level of N 2 than those of the other three systems. This study provides new insights into the adsorption of N 2 on metal-organic ligand species, in which the organic ligand dominates the reactivity, and it discovers new clues in designing effective transition metal carbine species for N 2 activation.

Rationale: Tetrandrine, the Q-marker in Stephaniae Tetrandrae Radix, was proven to present an obvious antitumor effect. Until now, the metabolism and antitumor mechanism of tetrandrine have not been fully elucidated., Methods: The metabolites of tetrandrine in rats were profiled using ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential antitumor mechanism of tetrandrine in vivo was predicted using network pharmacology., Results: A total of 30 metabolites were characterized in rats after ingestion of tetrandrine (10 mg/kg), including 0 in plasma, 7 in urine, 11 in feces, 9 in liver, 8 in spleen, 4 in lung, 5 in kidney, 5 in heart, and 4 in brain. This study was the first to show the metabolic processes demethylation, hydroxylation, and carbonylation in tetrandrine. The pharmacology network results showed that tetrandrine and its metabolites could regulate AKT1, TNF, MMP9, MMP2, PAK1, and so on by involving in proteoglycan tumor pathway, PI3K-Akt signaling pathway, tumor pathway, MAPK signaling pathway, and Rap1 signaling pathway., Conclusions: The metabolism features of tetrandrine and its potential antitumor mechanism were summarized, providing data for further pharmacological validation., (© 2023 John Wiley & Sons Ltd.)

Objective: To compare the efficacy of lower extremity three dimensional CT venography (CTV) and lower extremity ascending phlebography in evaluating recurrent varicose veins. Methods: A retrospective analysis was conducted on clinical data from 235 patients with unilateral recurrent varicose veins who were treated at the Department of Vascular Surgery,Beijing Shijitan Hospital,Capital Medical University, between January 2015 and December 2020.There were 112 males and 123 females, with an age of (62.5±11.4)years (range:24 to 75 years).Patients were stratified into two groups based on preoperative imaging examination:the CTV group (utilizing lower extremity venous ultrasound+lower extremity CTV) and the control group (employing lower extremity venous ultrasound+lower extremity ascending phlebography).The two groups were matched in a 1∶1 ratio using propensity score matching, resulting in 43 cases per group.Comparative analyses between the groups at the one-year postoperative follow-up were performed using independent sample t tests, Wilcoxon rank-sum tests, χ 2 tests, and linear regression analysis. Results: One year post-surgery,the CTV group exhibited a lower venous clinical severity score (VCSS) compared to the control group( M (IQR),3.0(4.3) vs. 4.0(5.8), Z =-2.038, P =0.040).Additionally, the chronic venous insufficiency patients' quality of life questionnaire (CIVIQ-20) scores were significantly higher in the CTV group than in the control group (89.0(8.0) vs. 82.5(17.0), Z =-2.627, P =0.010).Patients in the CTV group also experienced a shorter ulcer healing time compared to the control group (4.0(4.0) weeks vs. 12.0(7.0) weeks, Z =-3.217, P <0.01).Both groups showed no clinically symptomatic recurrent varicose veins or ulcers.However, they exhibited ultrasound-detectable varicose vein recurrence, with no statistically significant difference ( χ 2 =0.453, P =0.500).The number of diseased vessels requiring management based on ultrasound supplemented by CTV was 16, while the number supplemented by ascending phlebography was 7,with a statistically significant difference ( χ 2 =4.800, P =0.030).Linear regression analysis demonstrated that clinical-etiology-anatomy-pathology clinical grading and the preoperative imaging examination method exerted independent influences on VCSS and CIVIQ-20 during the one-year postoperative assessment. Conclusions: CTV-assisted ultrasound enables a direct and comprehensive evaluation and localization of diseased veins in patients with recurrent varicose veins.The utilization of lower extremity vein ultrasound combined with CTV-guided management of lower extremity vessels in minimally invasive treatment significantly improves patient prognosis, surpassing the assessment provided by ascending phlebography.

The nuclear receptor superfamily RAR is generally considered to play a crucial role in the development of tumors by regulating the transcription of target genes. Nevertheless, whether RARγ performs tumor-promoting or tumor-suppressing functions and its specific mechanism in thyroid carcinoma (TC) remain unknown. Here, our study demonstrated that RARγ was abnormally overexpressed in TC tissues compared with normal thyroid tissues. Moreover, RARγ expression was remarkably correlated with cell phenotypes such as cell proliferation, migration and invasion. Mechanistically, RARγ knockdown effectively decreased the phosphorylation levels of JAK1 and STAT3, leading to decreased expression of the membrane protein CD24. In a coculture system, TC cells with high levels of CD24 in the membrane were more likely to escape phagocytosis by macrophages via the combination of CD24 with the inhibitory receptor Siglec-10 in the membrane of macrophages. In contrast, the ability of macrophages to engulf TC cells was notably elevated through exogenous addition of CD24 antibody. Collectively, our study revealed a previously undiscovered molecular mechanism of RARγ in promoting the development of TC, shedding light on RARγ as a promising therapeutic target for TC., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Studies evaluating the characteristics of dual primary gastric and colorectal cancer (CRC) (DPGCC) are limited., Aim: To analyze the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with DPGCC., Methods: From October 2010 to August 2021, patients with DPGCC were retrospectively reviewed. The patients with DPGCC were divided into two groups (synchronous and metachronous). We compared the overall survival (OS) between the groups using Kaplan-Meier survival methods. Univariate and multivariate analyses were performed using Cox's proportional hazards model to identify the independent prognostic factors for OS., Results: Of the 76 patients with DPGCC, 46 and 30 had synchronous and metachronous cancers, respectively. The proportion of unresectable CRC in patients with synchronous cancers was higher than that in patients with metachronous cancers (28.3% vs 3.3%, P = 0.015). The majority of the second primary cancers had occurred within 5 years. Kaplan-Meier survival analysis showed that the patients with metachronous cancers had a better prognosis than patients with synchronous cancers ( P = 0.010). The patients who had undergone gastrectomy ( P < 0.001) or CRC resection ( P < 0.001) had a better prognosis than those who had not. In the multivariate analysis, synchronous cancer [hazard ratio (HR) = 6.8, 95% confidence interval (95%CI): 2.0-22.7, P = 0.002)] and stage III-IV gastric cancer (GC) [HR = 10.0, 95%CI: 3.4-29.5, P < 0.001)] were risk prognostic factor for OS, while patients who underwent gastrectomy was a protective prognostic factor for OS [HR = 0.2, 95%CI: 0.1-0.6, P = 0.002]., Conclusion: Regular surveillance for metachronous cancer is necessary during postoperative follow-up. Surgical resection is the mainstay of therapy to improve the prognosis of DPGCC. The prognosis appears to be influenced by the stage of GC rather than the stage of CRC. Patients with synchronous cancer have a worse prognosis, and its treatment strategy is worth further exploration., Competing Interests: Conflict-of-interest statement: All authors have no conflicts to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid-base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm-egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure., 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 Ji, Wang, Zhang, Hou, Luo, Xue, Shi, Jiao, Cui, He, Xue, Wen, Tang and Zhang.)

Clinical studies have demonstrated an association between high myopia (HM) and neuropsychiatric disorders; however, the underlying mechanism of the association is not clear. We used whole exome sequencing (WES) in combination with the Genetic Variants Classification Criteria and Guidelines published by the American College of Medical Genetics (ACMG) and bioinformatics analysis to clarify the interrelationship between candidate genes. Causative genes for ocular diseases (45.38%) followed by neuropsychiatric disorders (22.69%) accounted for the highest proportion of genes that exhibited high pathogenicity in HM patients were found. Four pathogenic gene mutations were identified according to ACMG guidelines: c.164&#95;165insACAGCA and c.C1760T in POLG, c.G1291A in COL5A1, and c.G10242T in ZNF469. Three causative genes for neuropsychiatric diseases, PTPRN2, PCDH15 and CDH23, were found to fall at the HM locus. The above results suggest that these genes may interact in high myopia and neuropsychiatric diseases., (© 2023. The Author(s).)

Objective: To analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA., Materials and Methods: A total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed., Result: There was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC ( P <0.05). As age and lesion size increased, the probability of SA significantly decreased, with a cut-off value of 36 years old and 10 mm, respectively. In the logistic regression analysis of the training set, age, nodule size, menopausal status, clinical symptoms, palpability of lesions, margins, internal echo, color Doppler flow imaging (CDFI) grading, and resistance index (RI) were statistically significant ( P <0.05). These indicators were included in the static and dynamic nomogram model, which showed high predictive performance, calibration and clinical value in both the training and validation sets., Conclusion: SA should be suspected in asymptomatic young women, especially those younger than 36 years of age, who present with small-size lesions (especially less than 10 mm) with distinct margins, homogeneous internal echo, and lack of blood supply. The nomogram model can provide a more convenient tool for clinicians., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Wei, Pang, Ni, Wu, Xiao, Zhang and Zhang.)

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.

Dinitrogen (N 2 ) activation and its chemical transformations are some of the most challenging topics in chemistry. Herein, we report that heteronuclear metal anions AuNbBO - can mediate the direct coupling of N 2 and O 2 to generate NO molecules. N 2 first forms the nondissociative adsorption product AuNbBON 2 - on AuNbBO - . In the following reactions with two O 2 molecules, two NO molecules are gradually released, with the formation of AuNbBO 2 N - and AuNbBO 3 - . In the reaction with the first O 2 , the generated nitrene radical (N ••- ) originating from the dissociated N 2 , induces the activation of O 2 . Subsequently, the second O 2 is anchored and forms a superoxide radical (O 2 •- ); this radical attacks the other N atom to form an N-O bond, releasing the second NO. The N ••- and O 2 •- radicals play key roles in the reactions. The mechanism adopted in this direct oxidation of N 2 by O 2 to NO can be labeled as a Zeldovich-like mechanism.

Background: To elucidate the role of Mucin1 (MUC1) in the trophoblast function (glucose uptake and apoptosis) of gestational diabetes mellitus (GDM) women through the Wnt/β-catenin pathway., Methods: Glucose uptake was analyzed by plasma GLUT1 and GLUT4 levels with ELISA and measured by the expression of GLUT4 and INSR with immunofluorescence and Western blotting. Apoptosis was measured by the expression of Bcl-2 and Caspase3 by Western blotting and flow cytometry. Wnt/β-catenin signaling measured by Western blotting. In vitro studies were performed using HTR-8/SVneo cells that were cultured and treated with high glucose (HG), sh-MUC1 and FH535 (inhibitor of Wnt/β-catenin signaling)., Results: MUC1 was highly expressed in the placental trophoblasts of GDM, and the Wnt/β-catenin pathway was activated, along with dysfunction of glucose uptake and apoptosis. MUC1 knockdown resulted in increased invasiveness and decreased apoptosis in trophoblast cells. The initial linkage between MUC1, the Wnt/β-catenin pathway, and glucose uptake was confirmed by using an HG-exposed HTR-8/SVneo cell model with MUC1 knockdown. MUC1 knockdown inhibited the Wnt/β-catenin signaling pathway and reversed glucose uptake dysfunction and apoptosis in HG-induced HTR-8/SVneo cells. Meanwhile, inhibition of Wnt/β-catenin signaling could also reverse the dysfunction of glucose uptake and apoptosis., Conclusions: In summary, the increased level of MUC1 in GDM could abnormally activate the Wnt/β-catenin signaling pathway, leading to trophoblast dysfunction, which may impair glucose uptake and induce apoptosis in placental tissues of GDM women., (© 2023. Sociedad de Biologia de Chile.)

Background: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery., Methods: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days., Results: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups., Conclusions: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium., Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257)., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)