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Fan Li,1– 3,* Zhengjian Wang,4,* Yinan Cao,1– 3 Boliang Pei,1– 3 Xinyu Luo,1– 3 Jin Liu,1– 3 Peng Ge,1– 3 Yalan Luo,1– 3 Shurong Ma,1,3 Hailong Chen1– 3 1Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 3Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 4Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shurong Ma; Hailong Chen, Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, Liaoning, 116011, People’s Republic of China, Tel +86-411-83635963, Fax +86-411-83622844, Email shurongma94@163.com; chenhailong@dmu.edu.cnAbstract: The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.Keywords: severe acute pancreatitis-associated acute lung injury, intestinal mucosal immune barrier, gut microbiota, gut-lung axis, migration of immune cells

Tao Luo,1 Yile Wang,1 Hailin Tang,1 Fei Zhou,2 Ying Chen,3 Bing Pei,4 Jinke Wang1 1State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, People’s Republic of China; 2School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, 521041, People’s Republic of China; 3School of Medical Technology, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 4Department of Clinical Laboratory, the Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, Jiangsu, 223800, People’s Republic of ChinaCorrespondence: Jinke Wang, State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, People’s Republic of China, Email wangjinke@seu.edu.cnBackground: The inflammatory diseases pose a great threat to human health. Variant anti-inflammatory agents have been therefore developed. However, the current anti-inflammatory drugs are still challenged by low response and side effects. There remain great unmet treatments to inflammatory diseases.Methods: In this work, we fabricate a recombinant adeno-associated virus (rAAV), rAAV-DMP-miR533, by packaging a DNA molecule DMP-miR533 into AAV, in which DMP is a NF-κB-activatable promoter composed of a NF-κB decoy and a minimal promoter and miR533 codes an artificial microRNA targeting NF-κB RELA. We evaluate the in vitro and in vivo anti-inflammatory effect of the virus with inflammatory cells and the mice of three typical inflammatory diseases including the dextran sulphate sodium-induced acute colitis, imiquimod-induced psoriasis, and collagen-induced arthritis.Results: We found that rAAV-DMP-miR533 had marked anti-inflammatory effect in both cells and mice. In addition, rAAV-DMP-miR533 showed biosafety in mice.Conclusion: This study thus provides a promising gene therapy to variant inflammatory diseases by directly targeting NF-κB, an established hub regulator of inflammation.Keywords: NF-κB, inflammation, therapy, AAV, microRNA

Jingyu Xu,1,* Zhenbiao Guan,2,* Xiaowei Wang,1,* Dazhi Sun,1 Yongjin Li,1 Bei Pei,1 Ye Lu,1 Liangxi Yuan,3 Xuan Zhang1 1Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, People’s Republic of China; 2Department of Respiration, Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China; 3Department of Vascular Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liangxi YuanDepartment of Vascular Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of ChinaEmail yuanlx116@163.comXuan ZhangDepartment of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, People’s Republic of ChinaEmail zhangx@smmu.edu.cnBackground and Objective: Neurotoxicity is a common side effect of oxaliplatin; the effect of current drugs such as methylcobalamin and gabapentine is not obvious. Astragaloside IV (AS-IV) is an important active ingredient of Astragali Radix, which can protect the nervous system and inhibit tumor growth to a certain extent. However, whether AS-IV can reduce oxaliplatin neurotoxicity and its molecular mechanism remain unclear.Methods: The network pharmacology method was used to determine the collective targets of AS-IV and oxaliplatin neurotoxicity. The model of neurotoxicity was established by intraperitoneal injection of oxaliplatin in rats. Bodyweight, mechanical withdrawal threshold (MWT), cold allodynia, and nerve conduction velocity (NCV) were examined, pathological changes were observed by hematoxylin-eosin staining, number of Nissl bodies were assessed by Nissl staining, the key collective targets were measured by spectrophotometry and immunohistochemistry.Results: Through network pharmacological analysis, 25 collective targets of AS-IV and oxaliplatin neurotoxicity were identified, mainly related to inflammation and oxidative stress. AS-IV could increase body weight, elevate MWT, and reduce cold allodynia of model rats, it also raised NCV. Neuropathology was improved and the number of Nissl bodies was increased by AS-IV administration. It reduced TNF-α, IL-6, and IL-1β in the spinal cord of model rats to inhibit inflammation; it also decreased MDA, raised SOD, CAT, and GSH-Px in the spinal cord of model rats to block oxidative stress.Conclusion: AS-IV improves oxaliplatin neurotoxicity by regulating neuroinflammation and oxidative stress; the results can provide a new perspective for the potential treatment strategy of oxaliplatin neurotoxicity.Keywords: network pharmacology, astragaloside IV, oxaliplatin neurotoxicity, neuroinflammation, oxidative stress

Summary: While videolaryngoscopy has resulted in better overall success rates of tracheal intubation, airway assessment is still an important prerequisite for safe airway management. This study aimed to create an artificial intelligence model to identify difficult videolaryngoscopy using a neural network. Baseline characteristics, medical history, bedside examination and seven facial images were included as predictor variables. ResNet‐18 was introduced to recognise images and extract features. Different machine learning algorithms were utilised to develop predictive models. A videolaryngoscopy view of Cormack‐Lehane grade of 1 or 2 was classified as 'non‐difficult', while grade 3 or 4 was classified as 'difficult'. A total of 5849 patients were included, of whom 5335 had non‐difficult and 514 had difficult videolaryngoscopy. The facial model (only including facial images) using the Light Gradient Boosting Machine algorithm showed the highest area under the curve (95%CI) of 0.779 (0.733–0.825) with a sensitivity (95%CI) of 0.757 (0.650–0.845) and specificity (95%CI) of 0.721 (0.626–0.794) in the test set. Compared with bedside examination and multivariate scores (El‐Ganzouri and Wilson), the facial model had significantly higher predictive performance (p < 0.001). Artificial intelligence‐based facial analysis is a feasible technique for predicting difficulty during videolaryngoscopy, and the model developed using neural networks has higher predictive performance than traditional methods. [ABSTRACT FROM AUTHOR]

Youwen Zhang, Deyin Tong, Daobiao Che, Bing Pei, Xiaodong Xia, Gaofeng Yuan, Xin Jin Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People’s Republic of China Abstract: The roles of ginsenoside compound K (CK) in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP)/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS) mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 µg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects. Keywords: ginsenoside CK, ascorbyl palmitate, TPGS, mixed micelles, anti-tumor therapy

Meiwen Yu,1,* Kan Wu,1,* Bing Pei,2 Degang Yang,2 Qiulin Wang,1 Hongsheng Wang,1 Jianping Shen,1 Liangbing Yan,1 Guochen Zhang1 1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for STD and Leprosy Control, China CDC, Nanjing, People's Republic of China; 2Department of Infectious Diseases, Shanghai Skin Disease Hospital, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: The reported number of registered leprosy patients worldwide declined with the introduction of multidrug therapy. However, the emergence of rifampicin resistance in leprosy patients engenders difficulties for an individual patient, and its dissemination could pose a threat to leprosy control. This study reports an elderly patient who was diagnosed with rifampicin-resistant lepromatous leprosy. This case indicates that inadequate treatment and poor compliance may eventually result in rifampicin resistance in Mycobacterium leprae and clinical relapse. Keywords: leprosy, rifampicin, drug resistance, elderly patient

This study aimed to investigate the effects of gastric cancer interstitial fluid (GCIF) on tumors and explore the possible mechanism of Xiaotan Sanjie decoction (XTSJ) on treatment of gastric cancer from the view of regulating microRNA-21 (miR-21) expression. The GCIF was extracted and identified by measuring the levels of interleukin-8 (IL-8), intercellular adhesion molecule 1 (ICAM-1) and miR-21. The effects of GCIF on the proliferation of SGC-7901 cells and tumor growing were assessed by cell counting kit-8 (CCK-8) assay and subcutaneously transplanted tumor-bearing nude mice model, respectively. Additionally, inhibition effect of XTSJ decoction on proliferation of SGC-7901 cells intervened by GCIF were assessed in vitro and anti-cancer effect of it was further assessed using orthotopic transplanted tumor-bearing nude mice model. The concentration of SGC-7901 gastric cancer cells were dependent on the concentration of the added GCIF. After 72 hours of continuous culture, the interstitial fluid had an obvious proliferative effect on the SGC-7901 tumor cells, which was the most significant in the high concentration group. XTSJ decoction could inhibit the growth-promoting effect (P < 0.01) of GCIF on gastric cancer cells. Intervention of the GCIF might promote the growth (P < 0.05) of the subcutaneously transplanted tumors in nude mice and decrease the net weight of the tumor-bearing nude mice (P < 0.05) after tumor removal. The GCIF was able to up-regulate the expression (P < 0.001) of miR-21 in the subcutaneously transplanted tumors. XTSJ decoction could downregulate the expression (P < 0.05) of miR-21 in SGC-7901 orthotopically transplanted tumors. XTSJ decoction can inhibit the multiplicative effect of GCIF on gastric cancer cells, growth of gastric tumor and promotion effect of GCIF on tumors, probably due to the down-regulating miR-21 expression in tumor tissues. [ABSTRACT FROM AUTHOR]

The notion of extended X-factor contribution has been proposed and evaluated recently as a tool to identify system capacity constraints based on machine group utilization and raw processing time. This provides a great convenience for factory-floor managers examining system capacity issues by using only local- or machine-level information. The purpose of this study is twofold: to study fundamental properties of the extended X-factor contribution measure augmented with availability, and to use this new measure to investigate resource allocation for optimizing mean cycle time. The availability-adjusted X-factor was first introduced in the context of local cycle time and its relation to allocation of personnel in individual machine groups. The availability-adjusted X-factor contribution measure developed and evaluated in the current study differs from the previous measure by its ability to identify capacity-constraining machines in the entire system. The measure presented herein is a more accurate indicator of capacity constraints than the extended X-factor contribution measures. With an objective to minimize cycle time or maximize throughput by properly allocating available resources, the results presented herein clearly demonstrate the effectiveness of this new measure to identify capacity-constraining machines. This study also uses availability as a decision variable for mean cycle time optimization. [ABSTRACT FROM AUTHOR]

The American Society for Histocompatibility and Immunogenetics HLA common and well‐documented (CWD) catalog, CWD 2.0.0 catalog and European Federation for Immunogenetics (EFI) CWD catalog have been published, which are useful for improving the accuracy of HLA genotyping in laboratories. Here, we studied the Chinese HLA CWD catalog. A total of 812 211 unrelated volunteer donors from the China Marrow Donor Program (CMDP) were analyzed. Six hundred seventy‐six alleles at the HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 loci were defined as CWD alleles in the Chinese population, including 159 common and 517 well‐documented alleles. The distribution of HLA alleles in the Chinese CWD catalog is different from that in the EFI CWD catalog. Thirty‐two percent (215/676) of CWD alleles in the Chinese CWD catalog are shared with those in the EFI CWD catalog. Fifty‐six percent (380/676) of alleles in the Chinese CWD catalog are not found in the EFI CWD catalog, while 655 alleles in the EFI CWD catalog are neither common nor well‐documented alleles in the Chinese CWD catalog. The Chinese CWD catalog described in this study may help to improve high‐resolution histocompatibility testing for CMDP‐accredited laboratories in China. However, to accommodate an increasing number of HLA alleles, this Chinese CWD catalog should be regularly updated. [ABSTRACT FROM AUTHOR]

Layered vanadium-based oxides have emerged as highly promising candidates for aqueous zinc-ion batteries (AZIBs) due to their open-framework layer structure and high theoretical capacity among the diverse cathode materials investigated. However, the susceptibility to structural collapse during charge-discharge cycling severely hampers their advancement. Herein, we propose an effective strategy to enhance the cycling stability of vanadium oxides. Initially, the structural integrity of the host material is significantly reinforced by incorporating bi-cations Na + and NH 4 + as "pillars" between the V 2 O 5 layers (NaNVO). Subsequently, surface coating with polyaniline (PA) is employed to further improve the conductivity of the active material. As anticipated, the assembled Zn//NaNVO@PA cell exhibits a remarkable discharge capacity of 492 mAh g -1 at 0.1 A g -1 and exceptional capacity retention up to 89.2 % after 1000 cycles at a current density of 5 A g -1 . Moreover, a series of in-situ and ex-situ characterization techniques were utilized to investigate both Zn ions insertion/extraction storage mechanism and the contribution of polyaniline protonation process towards enhancing capacity., (© 2024 Wiley-VCH GmbH.)

Background: Hyperprogressive disease (HPD) is a novel pattern of paradoxically rapid tumor progression, which often leads to early death, mostly in the first 2 months of treatment with immune checkpoint inhibitors (ICIs). Currently, there is no validated biomarker to assess patients at risk of HPD., Aim: The aim of this study was to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in HPD and establish a reliable variable to support clinicians in defining personalized treatment strategies., Methods: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched for studies published before 31 December 2023. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects or a fixed-effects model to evaluate the association between the NLR and the risk of HPD., Results: A total of 17 studies with 2,964 patients were included for meta-analysis. The incidence of HPD across different types of tumors ranged from 6.3% to 35.6%. In the pooled analysis of the NLR and HPD, we identified that the NLR significantly associated with the risk of HPD (OR = 0.65; 95% CI: 0.46 to 0.91; p = 0.01) ( I 2 = 52%, p = 0.007)., Conclusion: In the future, the NLR may serve as a remarkable biomarker for predicting the risk of HPD in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pei, Zhang, Lai and Chen.)

Study Design: Retrospective observational study., Objectives: Scoliosis is commonly observed in adolescents, with a world0wide prevalence of 0.5%. It is prone to be overlooked by parents during its early stages, as it often lacks overt characteristics. As a result, many individuals are not aware that they may have scoliosis until the symptoms become quite severe, significantly affecting the physical and mental well-being of patients. Traditional screening methods for scoliosis demand significant physician effort and require unnecessary radiography exposure; thus, implementing large-scale screening is challenging. The application of deep learning algorithms has the potential to reduce unnecessary radiation risks as well as the costs of scoliosis screening., Methods: The data of 247 scoliosis patients observed between 2008 and 2021 were used for training. The dataset included frontal, lateral, and back upright images as well as X-ray images obtained during the same period. We proposed and validated deep learning algorithms for automated scoliosis screening using upright back images. The overall process involved the localization of the back region of interest (ROI), spinal region segmentation, and Cobb angle measurements., Results: The results indicated that the accuracy of the Cobb angle measurement was superior to that of the traditional human visual recognition method, providing a concise and convenient scoliosis screening capability without causing any harm to the human body., Conclusions: The method was automated, accurate, concise, and convenient. It is potentially applicable to a wide range of screening methods for the detection of early scoliosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Immune nutrition, as an integral component of nutritional support therapy, has garnered significant attention and research in the treatment of gastrointestinal malignancies. Recent advancements in nutritional formulas containing components such as glutamine, omega-3 polyunsaturated fatty acids, and arginine have led to the development of what is now termed immune nutrition or pharmacological nutrition. These formulations go beyond traditional nutritional support, functioning more like nutritional supplements with pharmacological effects. Patients with gastrointestinal malignancies often experience malnutrition and metabolic disturbances, resulting in immune dysfunction, cytokine dysregulation, and endocrine abnormalities. These issues can compromise intestinal mucosal barrier function, affecting the efficacy and prognosis of anticancer therapies. Recent studies indicate that immune nutrition can modulate specific mechanisms involved in various immune and inflammatory pathways, thereby improving patients' immune status and treatment outcomes. While optimal patient selection, dosing, and timing of immune nutrition are still under investigation, its potential applications in oncology are promising. This article aims to analyze the existing evidence regarding the therapeutic benefits of immune nutrition in gastrointestinal malignancies, offering insights into its clinical standardization and application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Pei, Wu, Wang, Yu and Yang.)

Objective: To investigate the causal relationship between trimethylamine N-oxide (TMAO) and its precursors (betaine, carnitine, and choline) and pancreatic diseases based on the Mendelian randomization (MR) method., Methods: Genome-wide association study data of TMAO, betaine, carnitine, choline, acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC), and circulating immune cell characteristics (white blood cell, lymphocyte, monocyte, neutrophil, eosinophil and basophil) were collected. According to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines, the available genetic variants [single nucleotide polymorphism (SNP)] were strictly screened. The causal relationship between exposure (TMAO and its precursors) and outcomes (pancreatic diseases and circulating immune cell characteristics) was evaluated using inverse variance weighting (IVW), MR-Egger regression and weighted median. The reliability of the results was evaluated by sensitivity analysis based on MR-Egger regression, MR-PRESSO, Cochrane's Q test and leave-one-out method., Results: A total of 36 SNP associated with TMAO and its precursors were included. Five of these were associated with TMAO, 13 with betaine, 12 with carnitine, and 6 with choline. (1) MR analysis showed that TMAO may increase the risk of AP [odds ratio (OR) = 1.100, 95% confidence interval (95%CI) was 1.008-1.200, P = 0.032], and choline may reduce the risk of alcoholic acute pancreatitis (AAP; OR = 0.743, 95%CI was 0.585-0.944, P = 0.015). The analysis results of MR-Egger regression and weighted median were consistent with the IVW results. There is no evidence to support a causal relationship between TMAO and its precursors and the risk of CP and PC. Sensitivity analysis indicated that SNP analyzed by MR showed no heterogeneity and low pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. (2) There was a positive causal relationship between plasma TMAO level and circulating monocyte count (OR = 1.017, 95%CI was 1.000*-1.034, P = 0.048, * represented that the data was obtained by correcting to 3 decimal places from 1.000 1). The causal effect obtained by MR-Egger regression and weighted median analysis was consistent with the results of IVW. Sensitivity analysis illustrated SNP analyzed by MR showed no heterogeneity and pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results., Conclusions: TMAO and choline may change the risk of AP, and TMAO may contribute to the increase of circulating monocyte count in AP.

Hard carbon (HC) is a promising anode material in alkali metal ion batteries owing to its cost-effectiveness, abundant sources, and low working voltage. However, challenges persist in achiving prolonged cycling stability and consistent capacity, and the sodium storage mechanism in HC is still debated. Herein, an unreported biomass precursor, "sisal," for deriving hard carbon is developed. A series of sisal hemp-derived hard carbon with natural 3D porous channels are prepared. Through phase characterization and electrochemical testing, the relationship between microstructure and sodium storage capacity is elucidated, further confirming the suitability of the "adsorption-insertion-filling" mechanism for sodium storage properties in hard carbon materials. Without the need for any additional modification strategies, this biomass-derived hard carbon demonstrates excellent electrochemical performance in both sodium-ion and potassium-ion batteries (SIBs and PIBs). The as-prepared HC-1300 demonstrates excellent ion storage capability, delivering a high reversible capacity of 345.2 mAh g -1 in SIBs and 310 mAh g -1 in PIBs at 0.1 C. Moreover, it maintains a specific capacity of 237.3 mAh g -1 over 1200 cycles at 1 C when used in SIBs. The excellent cycling stability and superior rate performance are also presented in full cells, highlighting its potential for practical applications., (© 2024 Wiley‐VCH GmbH.)

This study was conducted with the primary objective of assessing the performance of cfDNA methylation in the detection of colorectal cancer (CRC). Five tumor tissue, 20 peripheral blood leucocyte, and 169 cfDNA samples were collected for whole-genome bisulfite sequencing (WGBS) analysis. Bioinformatic analysis was conducted to identify differentially methylated regions (DMRs) and their functional characteristics. Quantitative methylation-specific PCR (qMSP) was used to validate the methylation levels of DMRs in the tissues and leucocytes. cfDNA samples from CRC patients and healthy controls were used to evaluate the performance of the DMR analysis. WGBS analysis revealed a decrease in DNA methylation levels in the CpG context in CRC tumor tissues compared with adjacent normal tissues. A total of 132 DMRs in cfDNA were identified as potential markers for diagnosing CRC. In a cohort of 95 CRC patients and 74 healthy controls, a combination of the three DMRs ( DAB1 , PPP2R5C , and FAM19A5 ) yielded an AUC of 0.763, achieving 64.21% sensitivity and 78.38% specificity in discriminating CRC patients from healthy controls. This study provides insights into DNA methylation patterns in CRC and identifies a set of DMRs in cfDNA with potential diagnostic value for CRC. These DMRs hold promise as biomarkers for CRC detection, offering promise for non-invasive CRC diagnosis. Further research is warranted to validate these findings in larger cohorts.

Seaweed fertilizer, formulated primarily with seaweed extract as its main ingredient, has been extensively studied and found to significantly improve nutrient use efficiency, increase crop yield and quality, and enhance soil properties under field conditions. This growing body of evidence shows that seaweed fertilizer is a suitable option for sustainable agriculture in China. However, a comprehensive and quantitative analysis of the overall effects of seaweed fertilizer application in China is lacking. To address this gap, we conducted a meta-analysis of relevant studies on the effects of seaweed fertilizers under field conditions in China with MetaWin and SPSS software. Our analysis examined the effects of seaweed fertilizers on crop yield, quality, and growth under different preparation methods, application techniques, and regions. Our results showed that the application of seaweed fertilizer led to a significant average increase in crop yield of 15.17% compared with the control treatments. Root & tuber crops exhibited the most pronounced response, with a yield boost of 21.19%. Moreover, seaweed fertilizer application significantly improved crop quality, with elevations in the sugar-acid ratio (38.32%) vitamin C (18.07%), starch (19.65%), and protein (11.45%). In addition, plant growth parameters such as height, stem thickness, root weight, and leaf area showed significant enhancement with seaweed fertilizer use. The yield-increasing effect of seaweed fertilizers varied depending on their preparation and use method, climate, and soil of application location. Our study provides fundamental reference data for the efficient and scientific application of seaweed fertilizers in agricultural practices., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Within the global architecture, engineering, and construction industry, the use of Building Information Modeling (BIM) technology has significantly expanded. However, given the unique characteristics of road infrastructure, the application of BIM technology is still being explored. This article focuses on the Yuanchen Expressway, exploring innovative applications of BIM technology in comprehensive construction management. The project employs advanced technologies, including BIM, Geographic Information Systems (GIS), and the Internet of Things (IoT), to precisely identify critical nodes and breakthroughs. Supported by a detailed BIM model and a multi-level, diversified digital management platform, the project effectively addresses construction challenges in multiple tunnels, bridges, and complex interchanges, achieving intelligent construction innovation throughout the Yuanchen Expressway with BIM technology. By guiding construction through BIM models, utilizing a BIM+GIS-based management cloud platform system, and employing VR safety briefings, the project effectively reduces the difficulty of communication and coordination in project management, shortens the project measurement cycle, improves on-site work efficiency, and ensures comprehensive control and safety management. This article provides an exemplary case for the application of full-line construction management using BIM technology in the highway sector both in China and globally, offering new perspectives and strategies for highway construction management., (© 2024. The Author(s).)

Introduction: Gynecological diseases ranked second among new cases of noncommunicable diseases in women of reproductive age in 1990 and 2019 globally. The aim of this study was to estimate the disease burden of gynecological diseases and describe their trends in women of all ages from 1990 to 2019., Methods: Using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), authors examined the incidence, disability-adjusted life years, and deaths from gynecological diseases by age in 204 countries and territories worldwide from 1990 to 2019. Analyses were conducted in 2022., Results: Globally, the age-standardized incidence rate and age-standardized disability-adjusted life year rate (ASDR) of gynecological diseases decreased by -0.176% and -0.245%, respectively from 1990 to 2019. Low socioeconomic development index countries had the highest age-standardized incidence rate and ASDR in 2019. The age-specific incidence rate of gynecological diseases in women aged 15-29 years increased from 1990 to 2019, and the 20-24-year age group increased the greatest by 0.21%. Polycystic ovary syndrome and other types of benign disorders contributed to the major increase., Conclusions: Although the disease burden of gynecological diseases decreased slightly between 1990 and 2019 globally, it remained highest in low socioeconomic development index countries. The disease burden in 20-24-year age group exhibited the fastest growth, with polycystic ovary syndrome and other types of benign disorders playing a significant role. Urgent and effective measures should be taken to target different age groups, types of gynecological disease, and regions with high disease burdens., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The study aimed to examine the association between the systemic immune-inflammation index (SII), a contemporary metric of systemic inflammatory response, and biological aging, which are closely interconnected processes., Methods: This cross-sectional study utilized 10 cycles of data from the NHANES database spanning from 1990 to 2018. The study examined the relationship between the SII index, calculated as P * N/L, where P represents preoperative peripheral platelet count, N represents neutrophil count, and L represents lymphocyte count, and biological aging. Biological aging was assessed through various methods, such as phenotypic age, phenotypic age acceleration (PhenoAgeAccel), biological age, and biological age acceleration (BioAgeAccel). Correlations were analyzed using weighted linear regression and subgroup analysis., Results: Among the 7,491 participants analyzed, the average age was 45.26 ± 0.34 years, with 52.16% being female. The average phenotypic and biological ages were 40.06 ± 0.36 and 45.89 ± 0.32 years, respectively. Following adjustment for potential confounders, elevated SII scores were linked to increased phenotypic age, biological age, Phenotypic age acceleration, and Biological age acceleration. Positive correlations were observed between health behavior and health factor scores and biological aging, with stronger associations seen for health factors. In health factor-specific analyses, the β coefficient was notably higher for high BMI. The robust positive associations between SII scores and both phenotypic age and biological age in the stratified analyses were consistently observed across all strata., Conclusion: The evidence from the NHANES data indicate that SII may serve as a valuable marker for assessing different facets of aging and health outcomes, such as mortality and the aging process. Additional research is warranted to comprehensively elucidate the implications of SII in the aging process and its utility as a clinical instrument for evaluating and addressing age-related ailments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Ren, Li, Hu, Zhou, Sun, Pei, Li, Peng, Yu, Zhao, Huang, Chen and Huang.)

Objective: There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to examine the association between added sugar intake and frailty among American adults in the present cross-sectional study., Methods: This cross-sectional study is based on the National Health and Nutrition Examination Survey (NHANES) database. Data from NHANES spanning from 2007 to 2018 on frailty, added sugars, and covariates were collected. Added sugars were categorized into quartiles according to the recommended percentages by institutions. Weighted multivariable logistic regression was used to analyze the relationship between frailty and added sugars. Subgroup analysis was conducted based on sex, age, body mass index (BMI), smoking, alcohol consumption, hypertension, and diabetes status., Results: This study included 16,381 participants, with 13,352 (81.51%) in the non-frailty group and 3,029 (18.49%) in the frailty group. We found that added sugars were positively associated with frailty, and subgroup analysis showed that participants who were male, over the age of 60, had a low BMI, had previously smoked and consumed alcohol, had no hypertension, or had diabetes mellitus (DM) were more likely to be frail. Added sugar intake was positively associated with frailty. Subgroup analysis showed that the association was strongest in males, those aged >60, those with a low BMI, former smokers, former alcohol consumers, and people with no hypertension or DM. When added sugars are classified by energy percentage, populations with more than 25% of their energy coming from added sugars have similar results, with a higher prevalence of frailty., Conclusion: Added sugars are positively associated with a higher risk of frailty, and the association is stable among different populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ji, Qiu, Tao, Xu, Pei, Wu, Huang and Qian.)

Objective: To explore the potential pathogenic genes of intestinal metaplasia., Methods: Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January, 2022 to June, 2022, and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study. All the participants underwent gastroscopy and pathological examination, and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes (DEGs). The biological functions of the DEGs were analyzed using bioinformatics analysis, and qRT-PCR was used to validate the results., Results: Transcriptomic sequencing identified a total of 1373 DEGs, including 827 upregulated and 546 downregulated ones. The top 6 upregulated genes ( AGMAT , CCL25 , FABP1 , CDX1 , SPINK4 , and MUC2 ), ranked based on their significance and average expression level, were selected for validation, and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia ( P < 0.05)., Conclusion: AGMAT , CCL25 , FABP1 , CDX1 , SPINK4 , and MUC2 participate in the occurrence and development of intestinal metaplasia, and may serve as potential biomarkers for diagnosing intestinal metaplasia.

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ± 1.08 vs 3.00 ± 1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ± 1.43 vs 1.69 ± 1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ± 1.13 vs 2.80 ± 0.99, P = .022), preference for warmth and pressure (1.44 ± 1.06 vs 1.36 ± 1.10, P = .041), and poor appetite and indigestion (0.78 ± 0.66 vs 1.32 ± 0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Esophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection., Methods: To identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening., Findings: This review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma., Conclusion: In conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC., Competing Interests: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Wang, Pei, Wang, Xue and Zhao.)

Zirconium carbide (ZrC) ceramics have a high melting point, low neutron absorption cross section, and excellent resistance to the impact of fission products and are considered to be one of the best candidate materials for fourth-generation nuclear energy systems. ZrC ceramics with a high relative density of 99.1% were successfully prepared via pressureless sintering using a small amount of MoSi 2 as an additive. The influence of the MoSi 2 content on the densification behavior, microstructure, mechanical properties, and thermal properties of ZrC ceramics was systematically investigated. The results show that the densification of ZrC was significantly enhanced by the introduction of MoSi 2 due to the formation of a liquid phase during sintering. In addition, the ZrC grains were refined due to the pinning effect of the generated silicon carbide. The flexural strength and Vickers hardness of ZrC ceramics with 2.5 vol% MoSi 2 sintered at 1850 °C were 408 ± 12 MPa and 17.1 GPa, respectively, which were approximately 30% and 10% higher compared to the samples without the addition of MoSi 2 . The improved mechanical properties were mainly attributed to the high relative density (99.1%) and refined microstructure.

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264-0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056-1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234-2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022-1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382-0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085-0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To analyse the causal associations of different physical measures with osteoarthritis knee (KOA)., Methods: Exposure factors (weight, body mass index (BMI), body fat percentage, waist circumference, hip circumference, waist-hip ratio (WHR), and basal metabolic rate (BMR)), and outcome factor KOA were analyzed by inverse-variance weighted (IVW) method, along with heterogeneity test, sensitivity and pleiotropy analyses. Meta-analysis was used to combine the effect values of IVW methods in different data sources., Results: Weight, BMI, body fat percentage, waist circumference, hip circumference and BMR analyses showed causal association with increased KOA risk, while WHR analysis indicated a reduction of the incidence of KOA. P-value for all the results was less than 0.05 and F-value large than 20. All results were negative for heterogeneity tests and sensitivity analyses, and there was pleiotropy in weight and BMR. Meta-analysis results showed that the results of Odds Ratios (95% Confidence Intervals) for Weight (1.43(1.35-1.51)), BMI (1.40(1.10-1.78)), body fat percentage (1.56(1.44-1.68)), waist circumference (1.40(1.10-1.78)), hip circumference (1.37(1.30-1.44)), WHR (0.86(0.71-1.04)) and BMR (1.36(1.27-1.46) were consistent with the ones by Mendelian randomization analyses., Conclusions: Body fat percentage may be a better indicator of KOA than BMI. In addition, weight and BMR may have a causal effect in KOA, but WHR does not have a causal relationship. BMI, body fat percentage, waist circumference, and hip circumference has a causal effect on KOA., (© 2024. The Author(s).)

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice., Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer., Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer., Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-442/coif). The authors have no conflicts of interest to declare., (2024 Hepatobiliary Surgery and Nutrition. All rights reserved.)

The advent of tumor immunotherapy in patients has revolutionized the treatment of tumors and significantly improved survival rates for a wide range of tumors. However, the full therapeutic potential of immune checkpoint inhibitors (ICIs) has yet to be realized, as not all patients have a lasting survival benefit from them, and a significant proportion of patients show primary or acquired resistance to immunotherapy. Bifidobacterium is one of the most common probiotics, and its antitumor and immunomodulatory effects have been demonstrated in recent years, but its immunomodulatory effects in tumors, especially on ICIs and in combination, have not been extensively studied in clinical practice, and its effects on the immune system and the mechanisms that modulate immunotherapy are largely unknown. Therefore, this review will focus on the immunomodulatory effects of Bifidobacteria in malignancies and the possible mechanisms of action of Bifidobacteria on immunotherapy in the hope of providing a basis for further research and better application of Bifidobacteria in clinical practice., (© 2024. The Author(s).)

The effects of Ti doping on the microstructure and properties of SiC p /Al composites fabricated by pressureless infiltration were comprehensively investigated using first-principles calculations and experimental analyses. First-principles calculations revealed that the interface wetting and bonding strength in an Al/SiC system could be significantly enhanced by Ti doping. Subsequently, the Ti element was incorporated into SiC preforms in the form of TiO 2 and TiC to verify the influence of Ti doping on the pressureless infiltration performance of SiC p /Al composites. The experimental results demonstrated that the pressureless infiltration of molten Al into SiC preforms was promoted by adding TiC or TiO 2 due to the improved wettability. However, incorporating TiO 2 leads to the growth of AlN whiskers under a N 2 atmosphere, thereby hindering the complete densification of the composites. On the other hand, TiC doping can improve wettability and interface strength without deleterious reactions. As a consequence, the TiC-doped SiC p /Al composites exhibited excellent properties, including a high relative density of 99.4%, a bending strength of 287 ± 18 MPa, and a thermal conductivity of 142 W·m -1 ·K -1 .

Liquefied petroleum gas (LPG) is widely used for its cleanliness and high efficiency in industry and city life. In order to improve the suppression effect on LPG explosion, a constant volume combustion bomb was used to investigate the synergistic influence of N 2 /ultrafine water mist on the explosion and combustion characteristics of 6% premixed LPG/air gas. The results showed that (1) the effect of a single ultrafine water mist on suppressing LPG explosion is unstable. When the concentration of ultrafine water mist is low, the flame acceleration in the initial stage of explosion is promoted, and when the ultrafine water mist with a mass fraction of 420 g/m 3 is introduced, the maximum pressure rise rate increases. (2) The combination of N 2 /ultrafine water mist has a synergistic effect on LPG explosion. Compared to the individual suppression effects, the combination of N 2 /ultrafine water mist showed more effective suppression on the explosion pressure, flame propagation, and flame instability of LPG explosion. (3) Through the mechanism analysis, it is found that the combined action of N 2 / ultrafine water mist can better reduce the mole fraction and ROP peak of active free radicals such as H, O, and OH by inhibiting the main reaction of generating H, O, and OH radicals during the explosion of LPG, resulting in the reduction of flame free radicals in the explosion system, thus effectively inhibiting the chain reaction of ignition and explosion of LPG. This research can provide guidance for a better understanding and implementation of gas-liquid two-phase suppression technology for LPG explosion., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

MicroRNAs (miRNAs) are increasingly recognized as promising biomarkers for early disease diagnosis and prognosis. Therefore, the need for rapid, robust methods for multiplex miRNA detection in biological research and clinical diagnosis is crucial. This study introduces a novel multiplex miRNA detection method, SMOS-qPCR (Sensitive and Multiplexed One-Step RT-qPCR). The method integrates multiplexed reverse transcription and TaqMan-based qPCR into a single tube, employing a one-step operation on a real-time PCR system. We investigated the effect of 3' end phosphorylation of the Linker, Linker concentration and probe concentration on the SMOS-qPCR, resulted in a wide linear range from 1 fM to 0.1 zM (R 2  ≥ 0.99 for each miRNA), surpassing the capabilities of stem-loop RT-qPCR and SYBR Green One-step RT-qPCR. The method showed excellent performance in distinguishing mature miRNA from miRNA precursor, and successfully detected four miRNAs in a single tube without cross-interference. Its high specificity enables precise differentiation of less than 1% nonspecific signal. Finally, we demonstrated the effectiveness of the SMOS-qPCR system in detecting circulating miRNAs in serum samples, distinguishing between esophageal cancers and health individuals with high AUC values (>0.940). In conclusion, the proposed SMOS-qPCR system offers a straightforward and promising approach for miRNA profiling in future clinical applications., Competing Interests: Declaration of competing interest Authors Guodong Zhao, Kai Wang and Xiaoyu Liu are employed by Suzhou VersaBio Technologies Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Traditional growing rod (TGR) provides a corrective moment for deformed segments to straighten the spine, whose clinical efficacy has proven positive and growth-friendly. However, an insufficient understanding of orthopedic mechanisms can affect the development of clinical strategies. This research attempts to analyze the spine that has undergone four distraction operations: exploring the spinal orthopedic mechanism, including alignment, growth, and morphology. In this study, the spinal morphology curves were illustrated in three human planes to exhibit the changes in spinal alignment. The spinal growth characteristics were measured to discuss the unsynchronized and diminishing growth rate. The spinal deformations were evaluated to indicate asymmetric growth. As a result, the spinal alignment changes indicated the orthopedic process improved, but the re-unbalance occurred after multiple distractions. Then, unsynchronized growth existed in the superior and inferior segments, and the growth rate over every distraction diminished. Finally, asymmetric growth was indicated as the axial/circumferential growth ratio getting greater and the cuneate level approaching normal. Accordingly, a TGR is growth-friendly, but combining the osteotomy fusion of lumbar segments for severe early-onset scoliosis may be an excellent choice to solve the insufficient corrective stimulation. Regarding the distraction process, reshaping before the final fusion can fix the balance loss, and a prolonged distraction frequency fits the law of diminishing return. In conclusion, studying orthopedic mechanisms based on morphological measurement can guide clinical strategy optimization., (© 2023 Orthopaedic Research Society.)