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Abstract Background Postoperative pain is a prevalent symptom experienced by patients undergoing surgical procedures. This study aims to develop deep learning algorithms for predicting acute postoperative pain using both essential patient details and real-time vital sign data during surgery. Methods Through a retrospective observational approach, we utilized Graph Attention Networks (GAT) and graph Transformer Networks (GTN) deep learning algorithms to construct the DoseFormer model while incorporating an attention mechanism. This model employed patient information and intraoperative vital signs obtained during Video-assisted thoracoscopic surgery (VATS) surgery to anticipate postoperative pain. By categorizing the static and dynamic data, the DoseFormer model performed binary classification to predict the likelihood of postoperative acute pain. Results A total of 1758 patients were initially included, with 1552 patients after data cleaning. These patients were then divided into training set (n = 931) and testing set (n = 621). In the testing set, the DoseFormer model exhibited significantly higher AUROC (0.98) compared to classical machine learning algorithms. Furthermore, the DoseFormer model displayed a significantly higher F1 value (0.85) in comparison to other classical machine learning algorithms. Notably, the attending anesthesiologists' F1 values (attending: 0.49, fellow: 0.43, Resident: 0.16) were significantly lower than those of the DoseFormer model in predicting acute postoperative pain. Conclusions Deep learning model can predict postoperative acute pain events based on patients' basic information and intraoperative vital signs.

The 3D culture of intestinal organoids entails embedding isolated intestinal crypts and bone marrow mesenchymal stem cells within a growth factor-enriched matrix gel. This process leads to the formation of hollow microspheres with structures resembling intestinal epithelial cells, which are referred to as intestinal organoids. These structures encompass various functional epithelial cell types found in the small intestine and closely mimic the organizational patterns of the small intestine, earning them the name “mini-intestines”. Intestinal tumors are prevalent within the digestive system and represent a significant menace to human health. Through the application of 3D culture technology, miniature colorectal organs can be cultivated to retain the genetic characteristics of the primary tumor. This innovation offers novel prospects for individualized treatments among patients with intestinal tumors. Presently established libraries of patient-derived organoids serve as potent tools for conducting comprehensive investigations into tissue functionality, developmental processes, tumorigenesis, and the pathobiology of cancer. This review explores the origins of intestinal organoids, their culturing environments, and their advancements in the realm of precision medicine. It also addresses the current challenges and outlines future prospects for development.

Objective: The purpose of this scoping review was to map and identify studies describing the current state of research and teaching methods and evaluation systems for nurse anesthetists within China. Design: A wide-ranging search of multiple databases and gray literature was performed according to JBI criteria, employing predefined selection criteria and following PRISMA guidelines. Methods: This scoping review included studies published between 1988 and 2021 that explored the current state of clinical training and teaching methods for nurse anesthetists nationally and internationally. These articles were reviewed by four reviewers and content analysis was performed. Results: Fifty-two articles were included in the review. The results suggest that both simulation teaching in nursing education and Kolb's experiential learning cycle theory improve nursing staff teamwork, develop critical thinking skills, and improve core nursing competencies. Conclusions: High-fidelity simulation teaching based on Kolb's experiential learning cycle theory may be an effective teaching method to develop and improve the competence of nurse anesthesia monitors.

Precise control of cargo release is essential but still a great challenge for any drug delivery system. Irreversible electroporation (IRE), utilizing short high-voltage pulsed electric fields to destabilize the biological membrane, has been recently approved as a non-thermal technique for tumor ablation without destroying the integrity of adjacent collagenous structures. Due to the electro-permeating membrane ability, IRE might also have great potential to realize the controlled drug release in response to various input IRE parameters, which were tested in a red blood cell (RBC) model in this work. According to the mathematical simulation model of a round biconcave disc-like cell based on RBC shape and dielectric characteristics, the permeability and the pore density of the RBC membrane were found to quantitatively depend on the pulse parameters. To further provide solid experimental evidence, indocyanine green (ICG) and doxorubicin (DOX) were both loaded inside RBCs (RBC@DOX&ICG) and the drug release rates were found to be tailorable by microsecond pulsed electric field (μsPEF). In addition, μsPEF could effectively modulate the tumor stroma to augment therapy efficacy by increasing micro-vessel density and permeability, softening extracellular matrix, and alleviating tumor hypoxia. Benefiting from these advantages, this IRE-responsive RBC@DOX&ICG achieved a remarkably synergistic anti-cancer effect by the combination of μsPEF and chemotherapy in the tumor-bearing mice model, with the survival time increasing above 90 days without tumor burden. Given that IRE is easily adaptable to different plasma membrane-based vehicles for delivering diverse drugs, this approach could offer a general applicability for cancer treatment.

Abstract Neoantigens are emerging as attractive targets to develop personalized cancer vaccines, but their immunization efficacy is severely hampered by their restricted accessibility to lymphoid tissues where immune responses are initiated. Leveraging the capability of red blood cells (RBCs) to capture and present pathogens in peripheral blood to the antigen‐presenting cells (APCs) in spleen, we developed a RBC‐driven spleen targeting strategy to deliver DNA vaccine encoding hepatocellular carcinoma (HCC) neoantigen. The DNA vaccine‐encapsulating polymeric nanoparticles that were intentionally hitchhiked on the preisolated RBCs could preferentially accumulate in the spleen to promote the neoantigen expression by APCs, resulting in the burst of neoantigen‐specific T‐cell immunity to prevent tumorigenesis in a personalized manner, and slow down tumor growth in the established aggressively growing HCC. Remarkably, when combined with anti‐PD‐1, the vaccine achieved complete tumor regression and generated a robust systemic immune response with long‐term tumor‐specific immunological memory, which thoroughly prevented tumor recurrence and spontaneous lung metastasis. This study offers a prospective strategy to develop personalized neoantigen vaccines for augmenting cancer immunotherapy efficiency in immune “cold” HCC.

Abstract Background Esketamine is an antagonist of the N-methyl-D-aspartate receptor (NMDA receptor) that is widely used for multimodal analgesia. In addition to analgesia, sedation is another important effect of esketamine. However, data are limited regarding the sedation effect of esketamine during general anaesthesia. The objective of this study was to determine whether sedation with a subanaesthetic does of esketamine affects anaesthesia recovery. Methods Fifty patients, ASA I to II patient scheduled to laparoscopic cholecystectomy, were randomly assigned to receive a single bolus of esketamine 0.2 mg kg-1 (esketamine group) or placebo (control group). Propofol, sufentanil and rocuronium were used during total intravenous anaesthesia. The patients’ time of recovery from anaesthesia, postoperative pain, postoperative nausea and vomiting, and postoperative agitation were analysed. Results Data from 47 patients were analysed. The average time of anaesthetic recovery was 22.04 ± 1.48 min in the esketamine group(n = 23) and 17.54 ± 1.46 min in the control group(n = 24). The recovery time was significantly longer in the esketamine group. Postoperative pain in the PACU was lower in the esketamine group (NRS score range 0–2) than in the control group (NRS score range 0–3). There were no differences in postoperative nausea and vomiting, and postoperative agitation. Conclusion Subanaesthetic doses of esketamine can reduce postoperative pain in the PACU but delay the aesthetic recovery during the laparoscopic cholecystectomy, without affecting postoperative nausea and vomiting, and postoperative agitation. Trial registration The study was registered at the Chinese Clinical Trial Registry http://www.chictr.org.cn/ (Registration date: 20/11/2020; TrialID: ChiCTR2000040077 ).

Abstract Immune checkpoint blockade based on antibodies has shown great clinical success in patients, but the transitory working manner leads to restricted therapeutic benefits. Herein, a genetically engineered adenovirus is developed as the vector to deliver CRISPR/Cas9 (sgCas9‐AdV) to achieve permanent PD‐L1 gene editing with efficiency up to 78.7% exemplified in Hepa 1‐6 liver cancer cells. Furthermore, the sgCas9‐AdV is loaded into hydrogel made by silk fiber (SgCas9‐AdV/Gel) for in vivo application. The silk‐gel not only promotes local retention of sgCas9‐AdV in tumor tissue, but also masks them from host immune system, thus ensuring effectively gene transduction over 9 days. Bearing these advantages, the sgCas9‐AdV/Gel inhibits Hepa 1‐6 tumor growth with 100% response rate by single‐dose injection, through efficient PD‐L1 disruption to elicit a T cell‐mediated antitumor response. In addition, the sgCas9‐AdV/Gel is also successfully extended into other refractory tumors. In CT26 colon tumor characterized by poor response to anti‐PD‐L1, sgCas9‐AdV/Gel is demonstrated to competent and superior anti‐PD‐L1 antibody to suppress tumor progression. In highly aggressive orthotopic 4T1 mouse breast tumor, such a therapeutic paradigm significantly inhibits primary tumor growth and induces a durable immune response against tumor relapse/metastasis. Thus, this study provides an attractive and universal strategy for immunotherapy.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader implications due to its diverse tissue expression. Objective: This review aims to explore the multifaceted functions of PCSK9, highlighting its pro‐atherosclerotic effects, including its impact on circulating lipoprotein variables, non‐low‐density lipoprotein receptors, and various cell types involved in atherosclerotic plaque development. Conclusions: PCSK9 exhibits diverse roles beyond lipid metabolism, potentially contributing to atherosclerosis through multiple pathways. Understanding these mechanisms could offer new insights into therapeutic strategies targeting PCSK9 for cardiovascular disease management. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid‐lowering effects. Objective: This review aims to discuss existing and novel strategies of PCSK9 inhibition, providing an overview of established randomized controlled trials and ongoing outcome trials that assess the efficacy and long‐term safety of PCSK9 inhibitors. It also explores the evolving role of PCSK9 beyond lipid metabolism and outlines the pleiotropic actions of PCSK9 inhibition in various disorders and future directions including novel strategies to target PCSK9. Conclusion: PCSK9 inhibition shows promise not only in lipid metabolism but also in other disease processes, including atherosclerotic plaque remodeling, acute coronary syndrome, stroke, inflammation, and immune response. [ABSTRACT FROM AUTHOR]

We report the case of a man in his 50s who developed acute respiratory distress syndrome and right heart failure, necessitating intubation and initiation of inhaled nitric oxide (iNO) to decrease right ventricular afterload and improve the right heart function. The course was complicated by acute anaemia, with a diagnostic workup revealing methaemoglobinaemia and evidence of oxidative haemolysis indicated by blister and bite cells on peripheral blood film. The patient received conservative management, including successive red blood cell transfusion and gradual iNO weaning due to suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency. Discontinuation of iNO led to the resolution of both oxidative haemolysis and methaemoglobinaemia. Subsequent enzymatic assay, conducted 4months later, confirmed G6PD deficiency. This case highlights a rare instance of concurrent methaemoglobinaemia and oxidative haemolytic anaemia following iNO in a patient with underlying G6PD deficiency. [ABSTRACT FROM AUTHOR]

The new genus and species Pulvinatusia xuegulaensis (Brassicaceae) are described and illustrated. The species is a cushion plant collected from Xuegu La, Xizang, China. Its vegetative parts are most similar to those of Arenaria bryophylla (Caryophyllaceae) co-occurring in the same region, while its leaves and fruits closely resemble those of Xerodraba patagonica (Brassicaceae) from Patagonian Argentina and Chile. Family-level phylogenetic analyses based on both nuclear ITS and plastome revealed that it is a member of the tribe Crucihimalayeae, but the infra-/intergeneric relationships within the tribe are yet to be resolved.

ObjectiveAs the coronavirus disease 2019 (COVID-19) pandemic spread across Shanghai, China, in late February 2022 and protective measures to mitigate its impact were enacted, this study aimed to estimate how home quarantine affected the mental health of preschool children in Shanghai, China and explore the association between lifestyle factors and mental health during this special period.MethodsA cross-sectional online survey of 2,110 preschool students from Shanghai, China, was conducted during May 20–25,2022. Preschooler’ mental health (Strengths and Difficulties Questionnaire, SDQ) and daily activities were reported by parents.ResultsThe sample involved 2,110 children with a mean age of 4.65 years [standard deviation (SD): 0.91, range: 3–6 years]. Boys and children whose mother’s education level were college and high school had higher rate of mental health problems. Boys had significantly higher rates of peer problems and prosocial behaviors than girls. The 3-year-old group had significantly higher rates of prosocial behaviors than other groups. As compared to the Shanghai norm and the SDQ results of preschool children in Shanghai in 2019 (SH2019), there were a significant decrease in emotional symptoms score, as well as a significant increase in conduct problems score. Additionally, peer problems score significantly increased compared to SH2019. Decreased time spent on daily sleep was associated with the increased risk for preschoolers’ mental health problems.ConclusionThere was an increase in the frequency of emotional and behavioral problems, especially regarding conduct problems and peer problems, in preschool children during the COVID-19 home quarantine in Shanghai, China. Boys, younger preschool children and children whose mother’s education level were college and high school may be especially vulnerable to emotional and behavioral problems. It was also found that decreased time spent on sleep may aggravate preschool children’s mental health problems. It may be beneficial to differentiate and focus on conducting psychoeducation and implementing psycho-behavioral interventions to solve these issues.

Abstract Background Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown. Methods In a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1–0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients’ shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ 2 test, Student’s t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing. Results Of the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses—181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%; p = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28]; p = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6). Conclusions There is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit. Trial registration ClinicalTrials.gov ( NCT02442440 ; Registered on 13 April 2015).

Abstract Background Branch angle is a pivotal component of tea plant architecture. Tea plant architecture not only affects tea quality and yield but also influences the efficiency of automatic tea plant pruning. However, the molecular mechanism controlling the branch angle, which is an important aspect of plant architecture, is poorly understood in tea plants. Results In the present study, three CsLAZY genes were identified from tea plant genome data through sequence homology analysis. Phylogenetic tree displayed that the CsLAZY genes had high sequence similarity with LAZY genes from other plant species, especially those in woody plants. The expression patterns of the three CsLAZYs were surveyed in eight tissues. We further verified the expression levels of the key CsLAZY1 transcript in different tissues among eight tea cultivars and found that CsLAZY1 was highly expressed in stem. Subcellular localization analysis showed that the CsLAZY1 protein was localized in the plasma membrane. CsLAZY1 was transferred into Arabidopsis thaliana to investigate its potential role in regulating shoot development. Remarkably, the CsLAZY1 overexpressed plants responded more effectively than the wild-type plants to a gravity inversion treatment under light and dark conditions. The results indicate that CsLAZY1 plays an important role in regulating shoot gravitropism in tea plants. Conclusions The results provide important evidence for understanding the functions of CsLAZY1 in regulating shoot gravitropism and influencing the stem branch angle in tea plants. This report identifies CsLAZY1 as a promising gene resource for the improvement of tea plant architecture.

The commercial lithium-ion cell is based on layer-by-layer stacking of the cathode, porous separator, and anode laminates. The internal cathode/separator and anode/separator interfaces severely hamper Li-ion transport and displacement between the neighboring layers easily causes cell failure. Herein, we developed a novel interface-free cell configuration realized with a multifunctional polymer composite (LiPEAOB) which is used as both the electrode binder and the cell separator. The all-in-one cell configuration effectively eliminates the internal interfaces by holding all the cell components within the same LiPEAOB monolith. Meanwhile, the traditional porous separator is replaced by the nonporous and Li-conductive LiPEAOB membrane incorporated with nano Al2O3 filler. As such, we successfully overcome the two fundamental issues, namely (i) the high internal interfacial resistance and (ii) the cathode–anode cross-talk within the cell. The assembled LFP/graphite cell shows high rate capability, which can deliver a capacity of 104 mA h g−1 at a 10C rate. We demonstrate a significantly improved cycle life of the proposed cell compared to the traditional counterpart at different charge/discharge rates. The new paradigm for battery architecture within a continuous functional polymer matrix is important to revolutionize the state-of-the-art assembly of lithium-ion batteries with extremely high rates and long cycle life. [ABSTRACT FROM AUTHOR]

Saussurea wettsteiniana is a medicinally important herb endemic to Hengduan Mountains. Here, we report and characterize the complete chloroplast genome sequence of S. wettsteiniana to provide genomic resources useful for future study. The complete chloroplast genome is 152,631 bp in length, consisting of a large single copy and a small single copy of 83,552 bp and 18,637 bp, which were separated by a pair of inverted repeats of 25,221 bp. Totally 133 genes were annotated, including 87 protein-coding genes, 36 tRNA genes, and eight rRNA genes. We also detected two pseudo-genes (ycf1 and rps19). The overall GC content of the whole genome is 37.7%. The phylogenetic tree based on 23 complete plastomes indicated that S. wettsteiniana was closely related to S. involucrata of Compositae.