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Abstract Genetically lean and obese individuals have distinct intestinal microbiota and function. However, the underlying mechanisms of the microbiome heterogeneity and its regulation on epithelial function such as intestinal stem cell (ISC) fate remain unclear. Employing pigs of genetically distinct breeds (obese Meishan and lean Yorkshire), this study reveals transcriptome‐wide variations in microbial ecology of the jejunum, characterized by enrichment of active Lactobacillus species, notably the predominant Lactobacillus amylovorus (L. amylovorus), and lactate metabolism network in obese breeds. The L. amylovorus‐dominant heterogeneity is paralleled with epithelial functionality difference as reflected by highly expressed GPR81, more proliferative ISCs and activated Wnt/β‐catenin signaling. Experiments using in‐house developed porcine jejunal organoids prove that live L. amylovorus and its metabolite lactate promote intestinal organoid growth. Mechanistically, L. amylovorus and lactate activate Wnt/β‐catenin signaling in a GPR81‐dependent manner to promote ISC‐mediated epithelial proliferation. However, heat‐killed L. amylovorus fail to cause these changes. These findings uncover a previously underrepresented role of L. amylovorus in regulating jejunal stem cells via Lactobacillus‐lactate‐GPR81 axis, a key mechanism bridging breed‐driven intestinal microbiome heterogeneity with ISC fate. Thus, results from this study provide new insights into the role of gut microbiome and stem cell interactions in maintaining intestinal homeostasis.

Abstract The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient’s tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.

Abstract Background Endotracheal intubation is challenging during cardiopulmonary resuscitation, and video laryngoscopy has showed benefits for this procedure. The aim of this study was to compare the effectiveness of various intubation approaches, including the bougie first, preloaded bougie, endotracheal tube (ETT) with stylet, and ETT without stylet, on first-attempt success using video laryngoscopy during chest compression. Methods This was a randomized crossover trial conducted in a general tertiary teaching hospital. We included anesthesia residents in postgraduate year one to three who passed the screening test. Each resident performed intubation with video laryngoscopy using the four approaches in a randomized sequence on an adult manikin during continuous chest compression. The primary outcome was the first-attempt success defined as starting ventilation within a one minute. Results A total of 260 endotracheal intubations conducted by 65 residents were randomized and analyzed with 65 procedures in each group. First-attempt success occurred in 64 (98.5%), 57 (87.7%), 56 (86.2%), and 46 (70.8%) intubations in the bougie-first, preloaded bougie, ETT with stylet, and ETT without stylet approaches, respectively. The bougie-first approach had a significantly higher possibility of first-attempt success than the preloaded bougie approach [risk ratio (RR) 8.00, 95% confidence interval (CI) 1.03 to 62.16, P = 0.047], the ETT with stylet approach (RR 9.00, 95% CI 1.17 to 69.02, P = 0.035), and the ETT without stylet approach (RR 19.00, 95% CI 2.62 to 137.79, P = 0.004) in the generalized estimating equation logistic model accounting for clustering of intubations operated by the same resident. In addition, the bougie first approach did not result in prolonged intubation or increased self-reported difficulty among the study participants. Conclusions The bougie first approach with video laryngoscopy had the highest possibility of first-attempt success during chest compression. These results helped inform the intubation approach during CPR. However, further studies in an actual clinical environment are warranted to validate these findings. Trial registration Clinicaltrials.gov; identifier: NCT05689125; date: January 18, 2023.

This paper presents an experimental study on the compressive properties and creep behavior of Mg-Gd-Y-Zn-Mn-Nd alloy. A total of 42 specimens are prepared and tested, including 18 compression tests and 24 creep tests. The investigation aims to evaluate the influence of material orientation, temperature, and initial stress (for creep test only) on the compressive behavior of the Mg-Gd-Y-Zn-Mn-Nd alloy. First, the results of compression tests are analyzed, revealing insights into the anisotropic behavior, failure mode, yield strength, ultimate compressive strength, and failure strain of the Mg-Gd-Y-Zn-Mn-Nd alloy under compressive loading. Then, according to the experimental data from creep tests, where the steady creep rate, stress exponent and activation energy are calibrated. Furthermore, the creep mechanisms of the Mg-Gd-Y-Zn-Mn-Nd alloy under various material orientations are discussed. Additionally, the authors analyze and compare the Electron Backscatter Diffraction (EBSD) data of the Mg-Gd-Y-Zn-Mn-Nd alloy before and after undergoing compressive creep. Finally, based on the test results, a mathematical model is proposed to describe the development of compressive creep strain.

ABSTRACTIntestinal stem cells (ISCs) play a pivotal role in gut physiology by governing intestinal epithelium renewal through the precise regulation of proliferation and differentiation. The gut microbiota interacts closely with the epithelium through myriad of actions, including immune and metabolic interactions, which translate into tight connections between microbial activity and ISC function. Given the diverse functions of the gut microbiota in affecting the metabolism of macronutrients and micronutrients, dietary nutrients exert pronounced effects on host-microbiota interactions and, consequently, the ISC fate. Therefore, understanding the intricate host-microbiota interaction in regulating ISC homeostasis is imperative for improving gut health. Here, we review recent advances in understanding host-microbiota immune and metabolic interactions that shape ISC function, such as the role of pattern-recognition receptors and microbial metabolites, including lactate and indole metabolites. Additionally, the diverse regulatory effects of the microbiota on dietary nutrients, including proteins, carbohydrates, vitamins, and minerals (e.g. iron and zinc), are thoroughly explored in relation to their impact on ISCs. Thus, we highlight the multifaceted mechanisms governing host–microbiota interactions in ISC homeostasis. Insights gained from this review provide strategies for the development of dietary or microbiota-based interventions to foster gut health.

Basic leucine zipper (bZIP) transcription factors (TFs) regulate plant development, growth, and secondary metabolism. The formation of red bark of new ornamental cultivar 'Gantong 1' is regulated mainly by anthocyanin anabolism. However, it is unclear whether and which bZIP TFs are involved in this process. We identified 89 genes encoding CcbZIP TFs in Cinnamomum camphora genome that could be divided into 14 subfamilies with similar gene structures and conserved motifs. CcbZIP38 and CcbZIP57 were highly conserved compared to HY5 in Arabidopsis thaliana and they were highly expressed in the bark and leaves of 'Gantong 1' at different stages. The target gene enrichment analysis showed that indicating indirect involvement of CcbZIP38 and CcbZIP57 in the regulation of anthocyanin synthesis. Our study contributes to understanding the molecular mechanism of anthocyanin synthesis regulation by CcbZIP TFs and provides a theoretical basis for genetic improvement of ornamental traits in C. camphora.

Pancreatic cancer-related pain (PCRP) gains widespread attention for its high prevalence, extreme complexity, poor prognosis, and decreased survival rate. Current treatment of PCRP remains unsatisfactory since the underlying mechanism is not clear. The occurrence of PCRP is mainly related to the neurotropic nature of pancreatic cancer, and perineural invasion, neural remodeling and plasticity play important roles. Upon the understanding of PCRP mechanism, the management of PCRP is a multidisciplinary and multifaceted strategy. Traditional pain medications, invasive or intervention treatment, psychological support, integrative therapy, and palliative care are all the potential aspects for the management of PCRP.

Segmenting the left ventricle from the transgastric short-axis views (TSVs) on transesophageal echocardiography (TEE) is the cornerstone for cardiovascular assessment during perioperative management. Even for seasoned professionals, the procedure remains time-consuming and experience-dependent. The current study aims to evaluate the feasibility of deep learning for automatic segmentation by assessing the validity of different U-Net algorithms. A large dataset containing 1388 TSV acquisitions was retrospectively collected from 451 patients (32% women, average age 53.42 years) who underwent perioperative TEE between July 2015 and October 2023. With image preprocessing and data augmentation, 3336 images were included in the training set, 138 images in the validation set, and 138 images in the test set. Four deep neural networks (U-Net, Attention U-Net, UNet++, and UNeXt) were employed for left ventricle segmentation and compared in terms of the Jaccard similarity coefficient (JSC) and Dice similarity coefficient (DSC) on the test set, as well as the number of network parameters, training time, and inference time. The Attention U-Net and U-Net++ models performed better in terms of JSC (the highest average JSC: 86.02%) and DSC (the highest average DSC: 92.00%), the UNeXt model had the smallest network parameters (1.47 million), and the U-Net model had the least training time (6428.65 s) and inference time for a single image (101.75 ms). The Attention U-Net model outperformed the other three models in challenging cases, including the impaired boundary of left ventricle and the artifact of the papillary muscle. This pioneering exploration demonstrated the feasibility of deep learning for the segmentation of the left ventricle from TSV on TEE, which will facilitate an accelerated and objective alternative of cardiovascular assessment for perioperative management.

Abstract Background We aimed to investigate the effects of intermittent bolus paravertebral block on analgesia and recovery in open hepatectomy. Methods Eighty 18–70 years old, American Society of Anesthesiologists level I-III patients scheduled for hepatectomy with a J-shaped subcostal incision were enrolled and randomized to receive either intermittent bolus paravertebral ropivacaine (0.5% loading, 0.2% infusion) or 0.9% saline infusion at 1:1 ratio (25 ml loading before surgery, 0.125 ml/kg/h bolus for postoperative 48 h). The primary outcome was set as postoperative 48 h cumulative intravenous morphine consumption recorded by a patient-controlled analgesic pump. Results Thirty-eight patients in each group completed the study. The cumulative morphine consumptions were lower in the paravertebral block than control group at postoperative 24 (difference -10.5 mg, 95%CI -16 mg to -6 mg, P

Abstract Spinal ultrasonography has increasingly been used to image axial structures from the cervical to sacral region in recent years. In this work, we propose a comprehensive, systematic cervical scanning protocol that we refined as a route map, especially for beginners, to facilitate teaching, learning, diagnosis, and treatment in clinical pain practice. As a simple and clear tool to demonstrate the scanning protocol, the route map is delineated with rectangles, lines, and arrows. The rectangles represent the positions of the transducer, the arrows indicate route directions, and the lines show the routes of transducer movement. In this article, we describe cervical spinal ultrasonography to illustrate the route map interpretation, scanning protocol and target anatomical structures in detail. We believe that this comprehensive, clear, systematic, and portable route map will be beneficial for inexperienced pain clinicians and ultrasound beginners.

Abstract Objectives Previous studies have shown that there may be a positive correlation between serum uric acid levels and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is unclear. This study analyzed the relationship between impaired thyroid hormone sensitivity and serum uric acid levels, and presented them in quantitative form. Research design and methods This is a cross-sectional study of 4460 adults (male: 2300; female: 2160) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: thyroid feedback quantile-based index (TFQIFT4), thyroid stimulating hormone index (TSHI), and total thyroxine (T4) resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated total triiodothyronine (T3) resistance index (TT3RI) and TFQIFT3 indexes based on FT3 and TSH. Multiple linear regression models were used to evaluate the correlation between thyroid resistance index and serum uric acid, and the results were presented graphically as smooth curve fittings. Results Higher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. In conjunction with an increase in the thyroid hormone sensitivity index value, uric acid levels gradually increased as well. Furthermore, we found a segmented relationship between TT3RI and serum uric acid changes. The saturation and threshold analyses indicated that 18.85 was the turning point (logarithmic likelihood ratio test = 0.036). When TT3RI 18.85, there was a significant rise in serum uric acid with an increase in TT3RI [β(95% CI) 3.94 (0.94, 6.95), P = 0.010]. A further finding of the interaction test was that impaired thyroid hormone sensitivity and uric acid changes vary among different age groups and BMI levels. Conclusions Decreased sensitivity to thyroid hormones was associated with high levels of serum uric acid in people with normal thyroid function. The interaction test shows that different age groups and BMI groups impact the association between impaired thyroid hormone sensitivity and serum uric acid. Furthermore, smooth curve fitting revealed a segmental relationship between TT3RI and serum uric acid levels.

Ovarian cancer (OC) is one of the most lethal malignancies of the female reproductive system. OC patients are usually diagnosed at advanced stages due to the lack of early diagnosis. The standard treatment for OC includes a combination of debulking surgery and platinum-taxane chemotherapy, while several targeted therapies have recently been approved for maintenance treatment. The vast majority of OC patients relapse with chemoresistant tumors after an initial response. Thus, there is an unmet clinical need to develop new therapeutic agents to overcome the chemoresistance of OC. The anti-parasite agent niclosamide (NA) has been repurposed as an anti-cancer agent and exerts potent anti-cancer activities in human cancers including OC. Here, we investigated whether NA could be repurposed as a therapeutic agent to overcome cisplatin-resistant (CR) in human OC cells. To this end, we first established two CR lines SKOV3CR and OVCAR8CR that exhibit the essential biological characteristics of cisplatin resistance in human cancer. We showed that NA inhibited cell proliferation, suppressed cell migration, and induced cell apoptosis in both CR lines at a low micromole range. Mechanistically, NA inhibited multiple cancer-related pathways including AP1, ELK/SRF, HIF1, and TCF/LEF, in SKOV3CR and OVCAR8CR cells. NA was further shown to effectively inhibit xenograft tumor growth of SKOV3CR cells. Collectively, our findings strongly suggest that NA may be repurposed as an efficacious agent to combat cisplatin resistance in chemoresistant human OC, and further clinical trials are highly warranted.

Based on the parallel medical theory, this paper proposes the theory and method of parallel anesthesia, which aims to build an organic and unified intelligent full-cycle anesthesia platform composed of biological humans (medical personnel), robots (mechanical automation equipment) and digital humans (digital medical care) through artificial system modeling, computational experimental analysis and parallel execution of human-computer interaction.Starting from the current status quo and bottleneck of the development of anesthesiology, this paper first conceives multiple intelligent scene modes jointly constructed by biological humans, digital humans and robots in parallel anesthesia systems from the aspects of clinical anesthesia management, crisis management, scientific research, education and teaching, and operation management, and analyzes the role of biological humans in each scene and the complementary relationship between the three.At the same time, the improvement and improvement of parallel anesthesia on patients’ medical safety and medical work efficiency through computational experiments and the implementation correction mode of virtual and real combination are introduced.Finally, by analyzing the ethical issues in the construction of parallel anesthesia system, analyzing the boundary and regulations of automation and intelligent equipment participation in anesthesia, and taking “respect for life, fairness and transparency, efficient operation and labor saving” as the system criteria, an intelligent full-cycle anesthesia platform is established to reduce the repetitive work of medical mechanization, enhance the ability of intelligent decisionmaking assistance, and improve the level of refined treatment and management.

Introduction Early oral intake (EOI) is supposed to be safe and beneficial to patients’ recovery. However, the optimal timing of resuming oral intake has not been validated in thyroid and parathyroid surgery. On the other hand, a modified electromyography (EMG) endotracheal intubation protocol with real-time EMG monitoring during video laryngoscope/fibrescope-guided intubation was presented in 2022, which was regarded as an effective way to shorten the intubation time. We aimed to use Quality of Recovery-15 (QoR-15) questionnaire to compare the efficacy and safety of different EMG endotracheal intubation protocols combined with different postoperative oral intake strategy in thyroid and parathyroid surgery.Methods and analysis This prospective, single-centre, 2×2 factorial, randomised controlled trial will be conducted in the Peking Union Medical College Hospital (PUMCH), China. We plan to recruit 200 adult patients who will receive thyroid or parathyroid surgery under intraoperative nerve monitoring. Eligible patients will be randomly divided into two groups, which will receive either the modified intubation protocol (M group) or conventional intubation process (C group). After patients enter postanaesthesia care unit and Steward scores ≥4, they will be randomly divided into two groups again, which will receive early resumption of oral intake (E group) or delayed resumption of oral intake (D group). Patients will be followed up during hospitalisation and the QoR-15 questionnaire will be administered to compare the quality of recovery on the day before surgery (T0), the first day after surgery (T1) and the day of discharge (T2). The primary outcome is the QoR-15 scores at T1.Ethics and dissemination The study protocol has been approved by the Research Ethics Committee of Peking Union Medical College Hospital (IRB K-2501). All participants will give written informed consent before participation. The results from this study will be shared at conferences and disseminated in international journals.Trial registration number NCT05624463.

Background: In recent years, baroreflex activation therapy (BAT) has been utilized to treat heart failure with reduced ejection fraction (HFrEF). However, the supporting literature on its efficacy and safety is still limited. This investigation elucidates the effects of BAT in HFrEF patients to provide a reference for future clinical applications. Methods: This investigation follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. Relevant investigations on the use of BAT in HFrEF patients were searched and selected from 5 databases, including Web of Science, MEDLINE, PubMed, Embase, and Cochrane Library, from inception to December 2022. The methodological quality of eligible articles was assessed via the Cochrane risk of bias tool, and for meta-analysis, RevMan (5.3) was used. Results: Randomized controlled trials comprising 343 participants were selected for the meta-analysis, which revealed that in HFrEF patients, BAT enhanced the levels of LVEF (MD: 2.97, 95 % CI: 0.53 to 5.41), MLHFQ (MD: −14.81, 95 % CI: −19.57 to −10.06) and 6MWT (MD: 68.18, 95 % CI: 51.62 to 84.74), whereas reduced the levels of LVEDV (MD: −15.79, 95 % CI: −32.96 to 1.37) and DBP (MD: −2.43, 95 % CI: −4.18 to −0.68). Conclusion: It was concluded that BAT is an efficient treatment option for HFrEF patients. However, to validate this investigation, further randomized clinical trials with multiple centers and large sample sizes are needed.

Abstract Background Perioperative fluid management during major abdominal surgery has been controversial. Postoperative pancreatic fistula (POPF) is a critical complication of pancreaticoduodenectomy (PD). We conducted a retrospective cohort study to analyze the impact of intraoperative fluid balance on the development of POPF. Methods This retrospective cohort study enrolled 567 patients who underwent open pancreaticoduodenectomy, and the demographic, laboratory, and medical data were recorded. All patients were categorized into four groups according to quartiles of intraoperative fluid balance. Multivariate logistic regression and restricted cubic splines (RCSs) were used to analyze the relationship between intraoperative fluid balance and POPF. Results The intraoperative fluid balance of all patients ranged from -8.47 to 13.56 mL/kg/h. A total of 108 patients reported POPF, and the incidence was 19.0%. After adjusting for potential confounders and using restricted cubic splines, the dose‒response relationship between intraoperative fluid balance and POPF was found to be statistically insignificant. The incidences of bile leakage, postpancreatectomy hemorrhage, and delayed gastric emptying were 4.4%, 20.8%, and 14.8%, respectively. Intraoperative fluid balance was not associated with these abdominal complications. BMI ≥ 25 kg/m2, preoperative blood glucose

Srinath, Xie et al. analyze plasma metabolites present in patients with cerebral cavernous angiomas. Cholic acid and hypoxanthine are found in those with Cavernous Angioma disease whilst arachidonic and linoleic acids are found in Cavernous Angioma patients with symptomatic hemorrhage.

This paper presents experimental and numerical studies on the mechanical behavior of 5A90 aluminum-lithium alloy under combined tension and shear loading. Extensive experimental tests under tension and combined loading were conducted, and the influence of material direction, notch radius, and load angle were considered. Based on the test results, the yield strength, ultimate strength, fracture displacement, strain-stress curve, and displacement-stress curve were obtained, discussed, and analyzed. The finite element model (FEM) including fracture behavior was developed, and it was found that the established FEM can well predict the mechanical response of 5A90 aluminum-lithium alloy. Parametric studies were also conducted. Finally, by comparing with the results from FEM (and tests) and predictions from available design codes, the calculation method in Eurocode 9 was suggested to predict the combined strength of 5A90 aluminum-lithium alloy.

The facet joint injection is the most common procedure used to release lower back pain. In this paper, we proposed a deep learning method for detecting and segmenting facet joints in ultrasound images based on convolutional neural networks (CNNs) and enhanced data annotation. In the enhanced data annotation, a facet joint was considered as the first target and the ventral complex as the second target to improve the capability of CNNs in recognizing the facet joint. A total of 300 cases of patients undergoing pain treatment were included. The ultrasound images were captured and labeled by two professional anesthesiologists, and then augmented to train a deep learning model based on the Mask Region-based CNN (Mask R-CNN). The performance of the deep learning model was evaluated using the average precision (AP) on the testing sets. The data augmentation and data annotation methods were found to improve the AP. The AP50 for facet joint detection and segmentation was 90.4% and 85.0%, respectively, demonstrating the satisfying performance of the deep learning model. We presented a deep learning method for facet joint detection and segmentation in ultrasound images based on enhanced data annotation and the Mask R-CNN. The feasibility and potential of deep learning techniques in facet joint ultrasound image analysis have been demonstrated.

There is no doubt that seagrass beds constitute one of the most productive ecosystems in shallow coastal waters. Despite this, picoplankton in seagrass ecosystems has received relatively little attention. The purpose of this study was to compare picoplankton growth and mortality rates between seagrass and unvegetated habitats using chamber incubations. We tested two main hypotheses: (i) incubation with seagrass would result in higher bacterial growth rates due to increased DOM release from seagrass photosynthesis, and (ii) Synechococcus spp. would be lower in the presence of seagrass due to competition for inorganic nutrients. Bacterial growth rates were higher in seagrass chambers (2.44 d–1) than in non-seagrass chambers (2.31 d−1), respectively, suggesting that organic carbon coming from the seagrass community may support bacterial production. Furthermore, the growth rate of Synechococcus spp. was significantly lower in the seagrass treatment than in the non-seagrass treatment, likely reflecting nutrient competition with the seagrass. Small-scale chambers proved to be a useful tool for studying the factors controlling spatial and temporal patterns of picoplankton across different habitats. Furthermore, future studies should examine picoplankton growth over a wider range of spatial scales in seagrass beds and adjacent unvegetated sediment.

Background: At present, the pathogenesis of atherosclerosis has not been fully elucidated, and the diagnosis and treatment face great challenges. Cuproptosis is a novel cell death pattern that might be involved in the development of atherosclerosis. However, no research has reported the correlation between cuproptosis and atherosclerosis. Methods: The differential cuproptosis-related genes (CRGs) between atherosclerosis group and control group (A-CRGs) were discovered via differential expression analysis. The correlation analysis, PPI network analysis, GO, KEGG and GSEA analysis were performed to investigate the function of A-CRGs. The differences of biological function between atherosclerosis group and control group were investigated via immune infiltration analysis and GSVA. The LASSO regression, nomogram and machine learning models were constructed to predict atherosclerosis risk. The atherosclerosis molecular subtypes clusters were discovered via unsupervised cluster analysis. Subsequently, we used the above research methods to analyze the differential CRGs between clusters (M-CRGs) and evaluate the molecular subtypes identification performance of M-CRGs. Finally, we verified the diagnostic value for atherosclerosis and role in cuproptosis of these CRGs through the validation set and in vitro experiments. Results: Five A-CRGs were identified and they were mainly related to the biological function of copper ion metabolism and immune inflammatory response. The diagnostic models and nomogram of atherosclerosis based on 5 A-CRGs indicated that these genes had well diagnostic value. A total of two molecular subtypes clusters were obtained in the atherosclerosis group. There were many differences in biological functions between these two molecular subtypes clusters, such as mitochondrial outer membrane permeabilization and primary immunodeficiency. In addition, 3 M-CRGs were identified in the 2 clusters. Machine learning models and nomogram constructed based on M-CRGs showed that these genes had well molecular subtypes identification efficacy. In the end, the results of in vitro experiment and validation set confirmed the diagnostic value for atherosclerosis and role in cuproptosis of these genes. Conclusion: The cuproptosis may be a potential pathogenesis of atherosclerosis and CRGs may be promising markers for the diagnosis and molecular subtypes identification of atherosclerosis.

Introduction With COVID-19 bringing persistent impact on the worldwide population, perioperative management after SARS-CoV-2 infection needs to be revisited in the new period of different circulating coronavirus variants, vaccination status, increased reinfection rate and new disease control policies. This study aims to explore the association between time to surgery after COVID-19 diagnosis and the risk of postoperative morbidity and mortality.Methods and analysis This is a single-centre ambispective cohort study. Patients with preoperative SARS-CoV-2 infection who require inpatient surgical intervention from 1 December 2022 to 28 February 2023 will be included. Baseline assessment will include the time interval between preoperative SARS-CoV-2 infection and surgery, COVID-19 diagnosis and symptoms, vaccination status and routine preoperative evaluations. The primary outcome will be postoperative composite complications within 30 days after surgery. Association between post-COVID-19 interval and the outcomes will be explored using logistic regression after adjusting for confounding variables.Ethics and dissemination The study protocol has been approved by the Research Ethics Committee of Peking Union Medical College Hospital (IRB K3570). We aim to publish and disseminate the findings in peer-reviewed journals, scientific conferences and on social media.Trial registration number NCT05689840.

Abstract Background Soluble Klotho (S-Klotho) is an anti-aging protein mainly secreted by the kidneys. Hyperuricemia is prevalent among middle-aged and elderly individuals, which affects the development of various chronic diseases. However, there are relatively few studies investigating the association between plasma S-Klotho levels and hyperuricemia in middle-aged and elderly individuals. This study sought to clarify the relationship between S-Klotho and the risk of hyperuricemia in middle-aged and elderly people. Methods During 2007–2016, a total of 50,588 people participated in the National Health and Nutrition Examination Survey. Finally, 12,441 middle-aged and elderly people (aged 40–79) completed the soluble Klotho tests and had obtained complete data. S-Klotho was detected by ELISA kit, and the relationship between S-Klotho and hyperuricemia was assessed by multiple logistic regression. Hyperuricemia is defined as serum uric acid levels higher than or equal to 420 mmol/l in men and 360 mmol/l in women. Results In the middle-aged and elderly, plasma S-Klotho levels were negatively correlated with hyperuricemia, and there was a saturation effect. The inflection point of S-Klotho was 927.8 pg/ml (logarithmic likelihood ratio test = 0.002). When plasma S-Klotho 65 years: Q4 vs Q1, OR (95%CI): 0.72 (0.56, 0.92), P = 0.008)].When the level of S-Klotho was higher, the risk of hyperuricemia in men was lower than that in women [male: Q4 vs Q1, OR (95%CI): 0.67 (0.56, 0.81), P

Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s. For some patients, early diagnosis and surgical removal of melanomas is lifesaving, while other patients typically turn to molecular targeted therapies and immunotherapies as treatment options. Easy sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF, NRAS, and TERT genes, some of which can be therapeutically targeted. Though initially effective, many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory pathways. Immunotherapies represent an alternative to molecular targeted therapies. However, inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long term. As the protocol for combination therapies develop, so will our scientific understanding of the many pathways at play in the progression of melanoma. The future direction of the field may be to find a molecule that connects all of the pathways. Meanwhile, noncoding RNAs have been shown to play important roles in melanoma development and progression. Studying noncoding RNAs may help us to understand how resistance – both primary and acquired – develops; ultimately allow us to harness the true potential of current therapies. This review will cover the basic structure of the skin, the mutations and pathways responsible for transforming melanocytes into melanomas, the process by which melanomas metastasize, targeted therapeutics, and the potential that noncoding RNAs have as a prognostic and treatment tool.

The segmentation of knee joint is of great significance for diagnosis, guidance and treatment of knee osteoarthritis. However, manual delineation is time-consuming and labor-intensive since various anatomical structures are involved in the 3D MRI volume. Automatic segmentation of the whole knee joint requires no human effort, additionally can improve the quality of arthritis diagnosis and treatment by describing the details more accurately. Existing knee joint segmentation methods in the literature focus on only one or few structures out of many. In this paper, we study the feasibility of knee joint segmentation on MR images based on neural networks and deal with the following challenges: (1) end-to-end segmentation of 15 anatomical structures, including bone and soft tissue, of the whole knee on MR images; (2) robust segmentation of small structures such as the anterior cruciate ligament, accounting for about 0.036% of the volume data. Experiments on the knee joint MR images demonstrate that the average segmentation accuracy of our method achieves 92.92%. The Dice similarity coefficients of 9 structures were above 94%, five structures were between 87% and 90%, and the remaining one was about 76%.

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.

Abstract Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy with limited treatment options for recurrent or metastatic disease. Due to chemotherapy resistance and lack of targeted therapeutic approaches, current treatment options for the localized disease are limited to surgery and radiation, which fails to prevent locoregional recurrences and distant metastases in over 50% of patients. Approximately 20% of patients with ACC carry NOTCH-activating mutations that are associated with a distinct phenotype, aggressive disease, and poor prognosis. Given the role of NOTCH signaling in regulating tumor cell behavior, NOTCH inhibitors represent an attractive potential therapeutic strategy for this subset of ACC. AL101 (osugacestat) is a potent γ-secretase inhibitor that prevents activation of all four NOTCH receptors. While this investigational new drug has demonstrated antineoplastic activity in several preclinical cancer models and in patients with advanced solid malignancies, we are the first to study the therapeutic benefit of AL101 in ACC. Here, we describe the antitumor activity of AL101 using ACC cell lines, organoids, and patient-derived xenograft models. Specifically, we find that AL101 has potent antitumor effects in in vitro and in vivo models of ACC with activating NOTCH1 mutations and constitutively upregulated NOTCH signaling pathway, providing a strong rationale for evaluation of AL101 in clinical trials for patients with NOTCH-driven relapsed/refractory ACC.

Osteosarcoma (OS) is the most common primary malignancy of bone. Epigenetic regulation plays a pivotal role in cancer development in various aspects, including immune response. In this study, we studied the potential association of alterations in the DNA methylation and transcription of immune‐related genes with changes in the tumor microenvironment (TME) and tumor prognosis of OS. We obtained multi‐omics data for OS patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. By referring to curated immune signatures and using a consensus clustering method, we categorized patients based on immune‐related DNA methylation patterns (IMPs), and evaluated prognosis and TME characteristics of the resulting patient subgroups. Subsequently, we used a machine‐learning approach to construct an IMP‐associated prognostic risk model incorporating the expression of a six‐gene signature (MYC, COL13A1, UHRF2, MT1A, ACTB, and GBP1), which was then validated in an independent patient cohort. Furthermore, we evaluated TME patterns, transcriptional variation in biological pathways, somatic copy number alteration, anticancer drug sensitivity, and potential responsiveness to immune checkpoint inhibitor therapy with regard to our IMP‐associated signature scoring model. By integrative IMP and transcriptomic analysis, we uncovered distinct prognosis and TME patterns in OS. Finally, we constructed a classifying model, which may aid in prognosis prediction and provide a potential rationale for targeted‐ and immune checkpoint inhibitor therapy in OS.

Introduction Myofascial pain syndrome (MPS), especially in the neck and shoulder region, is one of the most common chronic pain disorders worldwide. Dry needling (DN) and pulsed radiofrequency (PRF) are the two effective methods for treating MPS. We aimed to compare the effects of DN and PRF in chronic neck and shoulder MPS patients.Methods and analysis This is a prospective, single-centre, randomised, controlled trial in a tertiary hospital. We plan to recruit 108 patients aged 18–70 years who are diagnosed with chronic MPS in the neck, shoulder and upper back regions and randomly allocate them to either the DN or PRF group at a 1:1 ratio. The DN group will receive ultrasound-guided intramuscular and interfascial DN 8–10 times per pain point or until local twitch responses are no longer elicited and 30 min of indwelling. The PRF group will receive ultrasound-guided intramuscular (0.9% saline 2 mL, 42℃, 2 Hz, 2 min) and interfascial (0.9% saline 5 mL, 42℃, 2 Hz, 2 min) PRF. Follow-up will be performed by the research assistant at 0, 1, 3 and 6 months postoperatively. The primary outcome is the postoperative 6-month pain visual analogue score (0–100 mm). Secondary outcomes include pressure pain threshold measured by an algometer, Neck Disability Index, depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), sleep status (Likert scale) and overall quality of life (36-Item Short Form Survey). Between-group comparisons will be analysed using either a non-parametric test or a mixed effects linear model.Ethics and dissemination This study was approved by the medical ethics committee of Peking Union Medical College Hospital (JS-3399). All participants will give written informed consent before participation. The results from this study will be shared at conferences and disseminated in international journals.Trial registration number NCT 05637047, Pre-results.

BackgroundThe risk of perioperative cardiac complications (PCCs) in patients living in high-altitude areas may increase with more adverse clinical outcomes due to the special geographical environment, which has not yet been studied. We aimed to determine the incidence and analyze risk factors for PCCs in adult patients undergoing major noncardiac surgery in the Tibet Autonomous Region.MethodsThis prospective cohort study enrolled resident patients from high-altitude areas receiving major noncardiac surgery in Tibet Autonomous Region People's Hospital in China. Perioperative clinical data were collected, and the patients were followed up until 30 days after surgery. The primary outcome was PCCs during the operation and within 30 days after the surgery. Logistic regression was used to build the prediction models for PCCs. A receiver operating characteristic (ROC) curve was used to evaluate the discrimination. A prognostic nomogram was constructed to generate a numerical probability of PCCs for patients undergoing noncardiac surgery in high-altitude areas.ResultsAmong the 196 patients living in high-altitude areas involved in this study, 33 (16.8%) suffered PCCs perioperatively and within 30 days after surgery. Eight clinical factors were identified in the prediction model, including older age (P = 0.028), extremely high altitude above 4,000 m (P = 0.442), preoperative metabolic equivalent (MET) 3 h (P = 0.043). The area under the curve (AUC) was 0.766 (95% confidence interval: 0.785–0.697). The score calculated from the prognostic nomogram predicted the risk of PCCs in high-altitude areas.ConclusionThe incidence of PCCs in resident patients living in high-altitude areas who underwent noncardiac surgery was high, and the risk factors included older age, high altitude above 4,000 m, preoperative MET 3 h. The prognostic nomogram of this study could help to assess the PCCs for patients in high-attitude areas undergoing noncardiac surgery.Clinical Trial RegistrationClinicalTrials.gov ID: NCT04819698.

Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization. Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation. Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing, effective management of large chronic skin wounds remains a clinical challenge. Keratinocytes are critical to re-epithelialization and wound healing. Here, we investigated whether exogenous keratinocytes, in combination with a citrate-based scaffold, enhanced skin wound healing. We first established reversibly immortalized mouse keratinocytes (iKera), and confirmed that the iKera cells expressed keratinocyte markers, and were responsive to UVB treatment, and were non-tumorigenic. In a proof-of-principle experiment, we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone, in a mouse skin wound model. Thus, these results demonstrate that iKera cells may serve as a valuable skin epithelial source when, combining with appropriate biocompatible scaffolds, to investigate cutaneous wound healing and skin regeneration.

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient’s show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

The subtropical region of China possesses abundant broad-leaf tree species resources; however, the anatomical properties and microstructure of the wood are still unclear, which restricts the processing and utilization of wood. In this study, 14 broad-leaf trees and four coniferous trees were selected. Wood anatomical indices and wood microanatomy were used to evaluate the wood properties using a comprehensive index method. The results have shown that Dalbergia assamica exhibited the highest wood basic density among the 14 broad-leaved tree species, accompanied by a significant fiber proportion and vessel lumen diameter but a small vessel proportion and a high number of wood rays. Conversely, Parakmeria lotungensis and Michelia chapensis had relatively low wood basic densities, rendering them less suitable as valuable broad-leaved wood sources. Altingia chinensis, Castanopsis kawakamii, and the remaining 11 tree species exhibited medium-level wood basic densities. The 14 broad-leaved tree species had medium-length fibers. Phoebe bournei, Dalbergia assamica, and Castanopsis kawakamii demonstrated relatively high fiber proportion. Altingia chinensis, Dalbergia assamica, and Castanopsis kawakamii exhibited a large number of wood rays, making their wood more susceptible to cracking, whereas other broad-leaved tree species possessed fewer wood rays. The findings have provided a scientific basis for the exploration of precious broad-leaved tree resources and wood use.

Background: With the development of an aging sociality, aging-related diseases, such as Alzheimer’s disease, cardiovascular disease, and diabetes, are dramatically increasing. To find small molecules from natural products that can prevent the aging of human beings and the occurrence of these diseases, we used the lifespan assay of yeast as a bioassay system to screen an antiaging substance. Isoquercitrin (IQ), an antiaging substance, was isolated from Apocynum venetum L., an herbal tea commonly consumed in Xinjiang, China. Aim of the Study: In the present study, we utilized molecular-biology technology to clarify the mechanism of action of IQ. Methods: The replicative lifespans of K6001 yeasts and the chronological lifespans of YOM36 yeasts were used to screen and confirm the antiaging effect of IQ. Furthermore, the reactive oxygen species (ROS) and malondialdehyde (MDA) assay, the survival assay of yeast under stresses, real-time polymerase chain reaction (RT-PCR) and Western blotting analyses, the replicative-lifespan assay of mutants, such as Δsod1, Δsod2, Δgpx, Δcat, Δskn7, Δuth1, Δatg32, Δatg2, and Δrim15 of K6001, autophagy flux analysis, and a lifespan assay of K6001 yeast after giving a mitophagy inhibitor and activator were performed. Results: IQ extended the replicative lifespans of the K6001 yeasts and the chronological lifespans of the YOM36 yeasts. Furthermore, the reactive nitrogen species (RNS) showed no change during the growth phase but significantly decreased in the stationary phase after treatment with IQ. The survival rates of the yeasts under oxidative- and thermal-stress conditions improved upon IQ treatment, and thermal stress was alleviated by the increasing superoxide dismutase (Sod) activity. Additionally, IQ decreased the ROS and MDA of the yeast while increasing the activity of antioxidant enzymes. However, it could not prolong the replicative lifespans of Δsod1, Δsod2, Δgpx, Δcat, Δskn7, and Δuth1 of K6001. IQ significantly increased autophagy and mitophagy induction, the presence of free green fluorescent protein (GFP) in the cytoplasm, and ubiquitination in the mitochondria of the YOM38 yeasts at the protein level. IQ did not prolong the replicative lifespans of Δatg2 and Δatg32 of K6001. Moreover, IQ treatment led to a decrease in Sch9 at the protein level and an increase in the nuclear translocation of Rim15 and Msn2. Conclusions: These results indicated that the Sch9/Rim15/Msn signaling pathway, as well as antioxidative stress, anti-thermal stress, and autophagy, were involved in the antiaging effects of IQ in the yeasts.

As one type of small modular nuclear reactor (SMR), the low-temperature nuclear heating reactors (LTNHRs), which have the characteristics of small size, a large power ratio, and good adaptability, can help provide energy in winter as well as reduce greenhouse gas emissions. Despite a growing number of LTNHRs worldwide, a mature legal regulatory system specifically targeting LTNHRs remains undeveloped. Further, few discussions have focused on the prospect of regulating LTHHRs and how national and international frameworks can respond to the new and increasing development of LTNHRs. Given the growing prominence of LTNHRs, this article aims to fill in the research gap by exploring possible regulatory pathways for LTNHRs and whether the existing nuclear regulatory frameworks developed for large reactors could be sufficiently applied to LTNHRs. The article examines and analyzes the prospects and potential challenges for regulating LTHHRs, specifically in the field of licensing. In particular, the article takes the Chinese nuclear legal system as an example to analyze whether the existing legislation and regulations can meet the new requirements for licensing of LTNHRs—given their unique characteristics—in China. Finally, this article proposes suggestions to address the obstacles to regulating LTNHRs, including amending the existing international regulatory framework, improving licensing supervision throughout environmental assessment and public participation, and strengthening international legal cooperation, to ensure the robust and reasonable development of LTNHRs worldwide.

Adenovirus (Ad) is a non-enveloped linear double-stranded DNA virus with >50 serotypes in humans. Ad vectors have been used as gene delivery vehicles to express transgenes, small interfering RNAs (siRNAs) for gene silencing, or CRISPR/Cas and designer nucleases for genome editing. Although several methods are used to generate Ad vectors, the Ad-making process remains technically challenging and time consuming. Moreover, the Ad-making techniques have not been improved for the past two decades. Gibson DNA Assembly (GDA) technology allows one-step isothermal DNA assembly of multiple overlapping fragments. Here, we developed a one-step construction of Ad (OSCA) system using GDA technology. Specifically, we first engineered several adenoviral recipient vectors that contain the ccdB suicide gene flanked with two 20-bp unique sequences, which serve as universal sites for GDA reactions in the Ad genome ΔE1 region. In two proof-of-principle experiments, we demonstrated that the GDA reactions were highly efficient and that the resulting Ad plasmids could be effectively packaged into Ads. Ad-mediated expression of mouse BMP9 in mesenchymal stem cells was shown to effectively induce osteogenic differentiation both in vitro and in vivo. Collectively, our results demonstrate that the OSCA system drastically streamlines the Ad-making process and should facilitate Ad-based applications in basic, translational, and clinical research.

As multipotent progenitor cells, mesenchymal stem cells (MSCs) can renew themselves and give rise to multiple lineages including osteoblastic, chondrogenic and adipogenic lineages. It's previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs. However, the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood. Emerging evidence indicates that noncoding RNAs, especially microRNAs, may play important roles in regulating MSC differentiation and bone formation. As highly conserved RNA binding proteins, Argonaute (AGO) proteins are essential components of the multi-protein RNA-induced silencing complexes (RISCs), which are critical for small RNA biogenesis. Here, we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs. We first found that BMP9 up-regulated the expression of Ago1, Ago2 and Ago3 in MSCs. By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes, we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs. Furthermore, we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization, and ectopic bone formation. Collectively, our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.

Abstract Background Early postoperative resumption of oral intake is supposed to be safe and beneficial to patients recovery. However, practitioners still have great confusion and disagreement about postoperative resumption of oral intake. This is a nationwide survey to investigate the current status of clinical practice and practitioners’ attitude toward postoperative resumption of oral intake along with their level of understanding of the ERAS guidelines. Methods An anonymous web-based survey questionnaire via mobile social platform was carried out in mainland China from December 11–20, 2020. The Wilcoxon signed rank test or chi-square test was used to compare the propensity of the resumption of oral intake. Results Totally 5370 responses were received, and 89% of them were from anesthesiology departments. The nature of the responses from clinical practitioners was highly diverse, but each of the three surgery types showed unique patterns of ERAS implementation. The respondents were more conservative regarding the commencement of both fluid and solid diets after gastrointestinal (GI) and hepato-pancreato-biliary (HPB) surgery than after non-abdominal (NA) surgery. Most respondents agreed that early oral intake is beneficial to reduce postoperative complications improve bowel recovery and overall outcome. 55% respondents considered themselves to have a better understanding of ERAS and tended to initiate oral intake early for all three surgery types (P

Organoids have immense potential as ex vivo disease models for drug discovery and personalized drug screening. Dynamic changes in individual organoid morphology, number, and size can indicate important drug responses. However, these metrics are difficult and labor-intensive to obtain for high-throughput image datasets. Here, we present OrganoID, a robust image analysis platform that automatically recognizes, labels, and tracks single organoids, pixel-by-pixel, in brightfield and phase-contrast microscopy experiments. The platform was trained on images of pancreatic cancer organoids and validated on separate images of pancreatic, lung, colon, and adenoid cystic carcinoma organoids, which showed excellent agreement with manual measurements of organoid count (95%) and size (97%) without any parameter adjustments. Single-organoid tracking accuracy remained above 89% over a four-day time-lapse microscopy study. Automated single-organoid morphology analysis of a chemotherapy dose-response experiment identified strong dose effect sizes on organoid circularity, solidity, and eccentricity. OrganoID enables straightforward, detailed, and accurate image analysis to accelerate the use of organoids in high-throughput, data-intensive biomedical applications.

Abstract Effective and safe liver‐directed gene therapy has great promise in treating a broad range of liver diseases. While adenoviral (Ad) vectors have been widely used for efficacious in vivo gene delivery, their translational utilities are severely limited due to the short duration of transgene expression and solicitation of host immune response. Used as a promising polymeric vehicle for drug release and nucleic acid delivery, carboxymethyl chitosan (CMC) is biocompatible, biodegradable, anti‐microbial, inexpensive, and easy accessible. Here, by exploiting its biocompatibility, controlled release capability and anti‐inflammatory activity, we investigated whether CMC can overcome the shortcomings of Ad‐mediated gene delivery, hence improving the prospect of Ad applications in gene therapy. We demonstrated that in the presence of optimal concentrations of CMC, Ad‐mediated transgene expression lasted up to 50 days after subcutaneous injection, and at least 7 days after intrahepatic injection. Histologic evaluation and immunohistochemical analysis revealed that CMC effectively alleviated Ad‐induced host immune response. In our proof‐of‐principle experiment using the CCl4‐induced experimental mouse model of chronic liver damage, we demonstrated that repeated intrahepatic administrations of Ad‐IL10 mixed with CMC effectively mitigated the development of hepatic fibrosis. Collectively, these results indicate that CMC can improve the prospect of Ad‐mediated gene therapy by diminishing the host immune response while allowing readministration and sustained transgene expression.

BackgroundIncreasing life expectancy of coronary artery bypass grafting (CABG) remains to be the major concern of cardiac surgeons. However, few studies have investigated the effect of postoperative skeletal muscle index (SMI) loss on prognosis. This study aims to evaluate the prognostic role of postoperative SMI loss ≥ 5% after CABG, in order to develop a novel nomogram to predict overall survival (OS).MethodsPatients underwent CABG via midline sternotomy from December 2015 to March 2021 were recruited in this study. Preoperative and postoperative 3 months chest computed tomography (CT) images were compared to assess changes in SMI at T12 level. Based on this, patients were classified into the presence or absence of SMI loss ≥ 5%. The association between postoperative SMI loss ≥ 5% and OS was then analyzed by the Kaplan-Meier curves and Cox model. A novel nomogram incorporating independent clinical prognostic variables was also developed.ResultsThe study enrolled 506 patients receiving CABG, of whom 98 patients experienced T12 SMI loss ≥ 5% and had a significantly worse OS (P < 0.0001). Multivariate regression analysis showed that T12 SMI per cent change (%T12 SMI-change) was an independent prognostic factor for OS (HR = 0.809, 95% CI = 0.749–0.874). The nomogram incorporating %T12 SMI-change with other variables was accurate for predicting OS. Besides, we also found that postoperative oral nutritional supplement (ONS) can rescue T12 SMI loss.ConclusionPostoperative SMI loss can predict survival outcome after CABG. The nomogram incorporating changes in SMI provides a superior performance than existing systems.

BackgroundMultiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome that presents as medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Experience is lacking in the anesthetic management of patients with this syndrome, particularly in those who present with pheochromocytoma receiving nonpheochromocytoma resection. We aimed to share our experience with the anesthetic management of MEN2A patients.MethodWe retrospectively enrolled 24 MEN2A patients who had received different types of surgery at Peking Union Medical College Hospital from January 1, 2015, to December 31, 2021. All the medical records were reviewed and analyzed.ResultIn total, 33 surgeries were performed in 24 MEN2A patients, with 20 surgeries comprising pheochromocytoma resection in 17 patients. Most of these patients who had received pheochromocytoma resection had typical hemodynamic changes during surgery and anesthesia. Regarding the other 13 nonpheochromocytoma resections in 13 patients, 10 were performed in patients without pheochromocytoma, and 3 surgeries were performed with either functional primary (1, bilateral tumor whose patient refused adrenalectomy) or metastatic pheochromocytoma (2, unresectable and malign tumors developed years after bilateral adrenalectomy). Regarding the latter 3 patients, 1 showed hypertension and tachycardia during anesthesia induction, 1 showed tachycardia during surgery and the other showed stability during surgery. Patients who had received pheochromocytoma resection (n=17) required longer postoperative hospital stays than those who had received nonpheochromocytoma resection without pheochromocytoma (n=10) (5.8 ± 1.8 vs. 4.3 ± 1.6; P = 0.031).ConclusionsWhenever MEN2A patients are diagnosed with pheochromocytoma, surgical resection of the pheochromocytoma remains the primary choice for MEN2A treatment. Nonpheochromocytoma surgeries performed with existing pheochromocytoma could be risky and require full caution and preparation.

Hereditary spherocytosis is a common red blood cell disease caused by an inherited red blood cell membrane defect, leading to a spherical shape and propensity for hemolysis. There is a lack of reports on intraoperative autologous blood transfusion for hereditary spherocytosis patients. We hereby report our recent experience with using the Cell Saver® system for intraoperative red blood cell salvage on a hereditary spherocytosis patient. There was a drastic increase in salvaged blood free-hemoglobin compared with the preoperative sample (82.6 mg/dl vs. 6.2 mg/dl) which indicated severe hemolysis. Although our patient recovered smoothly with a normal liver and renal function test and reported no adverse reaction during follow-up, it is noteworthy that severe hemolysis could happen during the cell salvage process for patients with hemolytic anemia, as there are similar reports on sickle cell anemia, beta-thalassemia intermedia, and paroxysmal nocturnal hemoglobinuria. Therefore, more clinical attention and thorough research should be drawn into this perspective, namely, hemolysis during the red blood cell salvage process for patients with hemolytic anemia.

During the last several decades, a number of transgenic or genetically modified tree varieties with enhanced characteristics and new traits have been produced. These trees have become associated with generally unsubstantiated concerns over health and environmental safety. We conducted transcriptome sequencing of transgenic Populus alba × P. berolinensis expressing the transcription factor JERF36 gene (ABJ01) and the non-transgenic progenitor line (9#) to compare the transcriptional changes in the apical buds. We found that 0.77% and 1.31% of the total expressed genes were significant differentially expressed in ABJ01 at the Daqing and Qiqihar sites, respectively. Among them, 30%–50% of the DEGs contained cis-elements recognized by JERF36. Approximately 5% of the total number of expressed genes showed significant differential expression between Daqing and Qiqihar in both ABJ01 and 9#. 10 DEGs resulting from foreign gene introduction, 394 DEGs that resulted solely from the environmental differences, and 47 DEGs that resulted from the combination of foreign gene introduction and the environment were identified. The number of DEGs resulting from environmental factors was significantly greater than that resulting from foreign gene introduction, and the combined effect of the environmental effects with foreign gene introduction was significantly greater than resulting from the introduction of JERF36 alone. GO and KEGG annotation showed that the DEGs mainly participate in the photosynthesis, oxidative phosphorylation, plant hormone signaling, ribosome, endocytosis, and plant-pathogen interaction pathways, which play important roles in the responses to biotic and abiotic stresses ins plant. To enhance its adaptability to salt-alkali stress, the transgenic poplar line may regulate the expression of genes that participate in the photosynthesis, oxidative phosphorylation, MAPK, and plant hormone signaling pathways. The crosstalk between biotic and abiotic stress responses by plant hormones may improve the ability of both transgenic and non-transgenic poplars to defend against pathogens. The results of our study provide a basis for further studies on the molecular mechanisms behind improved stress resistance and the unexpected effects of transgenic gene expression in poplars, which will be significant for improving the biosafety evaluation of transgenic trees and accelerating the breeding of new varieties of forest trees resistant to environmental stresses.

Abstract Background Patient safety incident (PSI) reporting has been an important means of improving patient safety and enhancing organizational quality control. Reports of anesthesia-related incidents are of great value for analysis to improve perioperative patient safety. However, the utilization of incident data is far from sufficient, especially in developing countries such as China. Methods All PSIs reported by anesthesiologists in a Chinese academic hospital between September 2009 and August 2019 were collected from the incident reporting system. We reviewed the freeform text reports, supplemented with information from the patient medical record system. Composition analysis and risk assessment were performed. Results In total, 847 PSIs were voluntarily reported by anesthesiologists during the study period among 452,974 anesthetic procedures, with a reported incidence of 0.17%. Patients with a worse ASA physical status were more likely to be involved in a PSI. The most common type of incident was related to the airway (N = 208, 27%), followed by the heart, brain and vascular system (N = 99, 13%) and pharmacological incidents (N = 79, 10%). Those preventable incidents with extreme or high risk were identified through risk assessment to serve as a reference for the implementation of more standard operating procedures by the department. Conclusions This study describes the characteristics of 847 PSIs voluntarily reported by anesthesiologists within eleven years in a Chinese academic hospital. Airway incidents constitute the majority of incidents reported by anesthesiologists. Underreporting is common in China, and the importance of summarizing and utilizing anesthesia incident data should be scrutinized.

Abstract Background This study aimed to identify the risk factors and evaluate the prognosis of unplanned reintubation caused by acute airway compromise (AAC) after general anesthesia. Methods This case-control study included surgical patients who underwent unplanned reintubation in the operating room and postanesthesia care unit after general anesthesia between January 1, 2014, and December 31, 2018. Cases due to AAC were matched 1:4 with randomly selected controls. Results A total of 123,068 patients were included, and reintubation due to AAC was performed in 36 patients (approximate incidence 0.03%). Univariable analysis revealed that male sex, age > 65, ASA physical status 3, sepsis, heart disease history, cerebral infarction history, Cormack Lehane grade, surgery type, fresh frozen plasma infusion, increased intubation duration, white blood cell count, and creatinine clearance rate were related to AAC-caused unplanned reintubation. Multivariable analysis revealed that age > 65 (OR = 7.50, 95% CI 2.47–22.81, P 65, ASA physical status 3, head-neck or thoracic surgery and high fluid load were found to be associated with AAC-caused unplanned reintubation.