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Tao Su,1,2,&ast; Ling Liu,3,&ast; Fan Meng,4,&ast; Hongzhen Wu,1,2 Tao Liu,1,2 Jun Deng,1,2 Xiang Peng,1,2 Min Zhi,1,2 Jiayin Yao1,2 1Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 4Digestive System Department, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhi; Jiayin Yao, Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26th Yuancun the Second Road, Guangzhou, Guangdong Province, 510655, People’s Republic of China, Email zhimin@mail.sysu.edu.cn; yjyin@mail3.sysu.edu.cnBackground: Ustekinumab (UST) is recommended as the first-line treatment for patients with moderate to severe Crohn’s disease (CD). However, the efficacy of certain patients may be suboptimal and necessitate intensive treatment or modification of the treatment regimen. We sought to establish a nomogram model to predict the short-term effectiveness of UST in moderate to severe CD patients.Methods: We established a derivation cohort comprising patients diagnosed with CD and treated with UST at the Sixth Affiliated Hospital of Sun Yat-sen University from May 2020 to July 2023. The patient data, including demographic and clinical characteristics as well as treatment details, were systematically collected. The achievement of clinical remission (defined as Crohn’s Disease Activity Index, CDAI < 150, without corticosteroid usage) after induction therapy was the endpoint observed during follow-up. Potential predictors were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Subsequently, a multivariate logistic regression analysis was conducted to construct a nomogram model. The predictive accuracy and discriminative power of the model were assessed by Receiver Operating Characteristics (ROC) curves and calibration curves. Decision curve analysis (DCA) was employed to assess the clinical application value of the model.Results: 162 patients were included in the derivation cohort. The predictor’s selection was according to the minimum criteria. Prognostic factors, including duration, body mass index (BMI), smoking, extraintestinal manifestations (EIMs), perianal lesions (P), history of Vedolizumab therapy, and albumin levels (ALB), were identified and included in the nomogram. The model showed good discrimination and calibration on internal validation based on the bootstrap method (C-index: 0.843, 95% confidence interval: 0.768– 0.903). Moreover, DCA demonstrated that the nomogram was clinically beneficial.Conclusion: We constructed a practical tool to assist clinicians in identifying moderate to severe CD patients who are expected to have a good clinical response to UST, promoting personalized treatment and the development of precision medicine.Keywords: Ustekinumab, Crohn’s disease, clinical remission, nomogram

Mengjia Zhi,1 Linlin Hu,1 Fangli Geng,2 Ningjun Shao,3 Yuanli Liu1 1School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100710, People’s Republic of China; 2Ph.D. Program in Health Policy, Harvard University Graduate School of Arts and Sciences, Cambridge, MA, USA; 3Jinhua Healthcare Security Administration, Zhejiang, 321000, People’s Republic of ChinaCorrespondence: Linlin Hu; Yuanli Liu, School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100710, People’s Republic of China, Tel/Fax +86 65105830, Email hulinlin@sph.pumc.edu.cn; Liuyuanli_pumc@163.comPurpose: Post-acute care is fast developing in China, yet a payment system for post-acute care has not been established. As stroke is the leading cause of mortality and disability in China, patients constitute a large share of post-acute-care patients among all hospitalized patients. This study was to identify the cost determinants and establish a case-mix classification of the post-acute care system for stroke patients in China.Patients and Methods: A total of 5401 post-acute stroke patients in seven hospitals of Jinhua City from January 2018 to December 2020 were selected. Demographic characteristics, medical status, functional measures (eg, the Barthel Index, Mini-Mental State Examination, Gugging Swallowing Screen, Hamilton Depression Scale), and cost data were extracted. Generalized linear model (GLM) and quantile regression (QR) were conducted to determine the predictors of cost, and a case-mix classification model was established using the decision-tree analysis.Results: The GLM regression revealed that gender, tracheostomy, complication or comorbidity (CC), activities of daily living (ADL), and cognitive impairment were the main variables significantly affecting the hospitalization expenses of post-acute stroke patients. The QR model showed that the gender, tracheostomy and CC factors had a more significant impact on per diem costs on the upper quantiles. In contrast, cognitive impairment had a more substantial effect on the lower quantiles, and ADL significantly impacted the central quantile. Using tracheostomy, CC, and ADL as node variables of the regression tree, 12 classes were generated. The case-mix classification performed reliably and robustly, as measured by the reduction in the variation statistic (RIV=0.46) and class-specific coefficients of variation (CV less than 1.0; range: 0.18– 0.81).Conclusion: QR has strengths in comprehensively identifying cost predictors across cost groups. Tracheostomy, CC, and ADL significantly can predict the expenses of post-acute care for stroke patients. The established case-mix classification system can inform the future payment policy of post-acute care in China.Keywords: cost, case-mix, post-acute care, stroke, quantile regression, decision-tree model

Wenlei Chen,1 Min Zhi,1 Zujian Feng,2 Pengfei Gao,1 Yuan Yuan,1 Congcong Zhang,1 Yonglan Wang,1 Anjie Dong2 1Department of Periodontology, School and Hospital of Stomatology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People’s Republic of China Objective: The aims of this study were to 1) encapsulate ibuprofen (IBU) and basic fibroblast growth factor (bFGF) in a thermosensitive micellar hydrogel, 2) test the biological properties of this in situ drug delivery system, and 3) study the effect of hydrogel in promoting soft tissue healing after implant surgery and its anti-inflammatory function as an early local treatment of peri-implantitis.Materials and methods: A thermosensitive micellar hydrogel was prepared from amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone) (PECT) nanoparticles and tested in vitro using a scanning electron microscope, rheometer, UV spectrophotometer, HPLC, and transmission electron microscope.Results: The bFGF + IBU/PECT hydrogel formed a stable, water-dispersible nanoparticle core shell that was injectable at room temperature, hydrogel in situ at body temperature, and provided sustained release of both hydrophilic and hydrophobic drugs. The hydrogel promoted the proliferation and adhesion of human gingival fibroblasts, upregulated the expression of adhesion factors such as vinculin proteins, and showed anti-inflammatory properties.Conclusion: In situ preparation of IBU- and bFGF-loaded PECT hydrogel represents a promising drug delivery system with the potential to provide early local treatment for peri-implantitis. Keywords: thermosensitive hydrogel, nanoparticles, dual drugs, peri-implantitis

Abstract Background Uncorrected refractive error (URE) is one of the main causes of visual impairments. URE may reduce interaction and learning in the classroom, leading to social isolation, irreversible amblyopia, lack of external knowledge, and restrictions on education and employment opportunities. Our aim was to investigate the prevalence and related factors of URE in adolescents using epidemiological surveys and questionnaire surveys related to lifestyle habits. Methods A cross-sectional school-based study was conducted in Nantong, China, including adolescents 12–19 years of age from 16 schools. URE was defined as presenting visual acuity worse than 6/12 and improving to ≥ 1 lines after correction in either eye. Univariate and multivariate logistic regression analyses were used to investigate specific correlations between URE and related lifestyle parameters. Non-cycloplegic autorefraction was assessed for each adolescent. Results A total of 2,910 adolescents were analyzed, of which 50.3% (n = 1,465) were male, and 49.7% (n = 1,445) were female. The mean age was 15.23 ± 1.77 years. The overall prevalence of URE was 23.7%. The total prevalence of REC and eREC was 85.1% and 71.7%, respectively, and both of them showed an increasing trend with age (Ptrend = 0.018 and Ptrend = 0.019, respectively). A higher prevalence of URE was related to myopia, anisometropia, and increased daily use of electronic products. Timely visual examination by medical institutions, more extracurricular homework, and older age were protective factors for URE. Among the 689 adolescents with URE, 362 (52.5%) did not receive any refractive correction, and 327 (47.5%) used corrected glasses. Conclusion URE was highly prevalent among adolescents in China. Myopia was the most important risk factor for URE. The impact of anisometropia and increased daily use of electronic devices on URE was significant. Timely visual examinations by medical institutions served as an effective protective factor against URE. Further research on adjusting intervention strategies is therefore needed to eliminate preventable visual impairments.

Peer review of radiation treatment (RT) plans in chart rounds is an integral part of radiation oncology clinical practice, ensuring optimization of treatment plans with respect to patient safety and disease control outcomes. Our institution previously conducted general chart rounds for all disease subsites. In September 2023, we implemented a bi-monthly, head and neck (HN)-specific chart rounds for attending physicians sub-specialized in HN radiation oncology. This study evaluates the clinical and educational impact of HN chart rounds on residents and attending physicians at our institution. An electronic, anonymous survey was distributed between February 2024 and March 2024 amongst residents (N = 8), and HN attending physicians (N = 14) at four radiation therapy centers within an integrated health care system. The survey was comprised of multiple choice, 5-point Likert scale, and open response questions focusing on the clinical and educational quality, perceived benefits and challenges of implementation, and the resulting impact on trainee and attending physician clinical practice. Participant response rate was 73%. Responding attending physicians had been in practice for 1-3 years (33%), 4-9 years (33%), or >10 years (33%). Eighty-eight percent of participants were moderately or extremely satisfied with the overall clinical quality of HN chart rounds, and 81% of participants were moderately or extremely satisfied with the educational quality of HN chart rounds. Target volume delineation discussion (100%), practice pattern observation across different centers (88%), and direct feedback on RT plans (69%) were reported as the most educational. Attending physicians also reported perceived educational benefit from having dedicated time to focus on more complex RT plans (78%) and assessing resident knowledge (78%). Fifty-six percent of participants reported making changes in their clinical practice, and 81% reported improvement in quality control and patient safety since implementation of HN chart rounds. Peer review resulted in minor plan adjustments for 69% of physicians and plan of care changes (i.e. requiring additional imaging, biopsy, or tumor board discussion) for 6% of physicians. No major plan adjustments were reported. Eighty-one percent of participants advocated for increased time and frequency of HN chart rounds for more in-depth discussion, and 31% requested plan review to be scheduled prior to the start of radiation treatment to accommodate potential major changes in treatment plan without treatment interruptions. Implementation of HN-specific chart rounds in a high-volume multi-center institution was perceived by physicians to improve quality assurance and patient safety. Resident and attending physician education was felt to be enhanced through exchange of clinical knowledge and practice variation. [ABSTRACT FROM AUTHOR]

Abstract As one of the most prevalent tumors, colorectal cancer (CRC) owns complex pathogenesis and the high recurrence rate significantly influence the prognosis of patients with KRAS mutant CRC, to discovery the crosstalk among KEAP1‐NFE2L2 and oncogenic KRAS as the potential prognostic biomarkers in CRC, which might be used to develop novel and effective therapeutics. By using bioinformatics analysis, we explored and identified key genes as the predicted targets in the crosstalk among KEAP1 oncogenic signatures of KRAS mutation that were linked with development, metastasis, and poor prognosis in CRC. We further investigated the correlations between the clinical characteristics and expressions of prognostic genes among the KRAS and KEAP1‐related key hub genes in CRC, which as predicted targets to find the potential herbal ingredients in HERB database, further to verify the active herbal ingredients could regulate the key targets that related to KEAP1‐NFE2L2 in KRAS mutant CRC. The newest TCGA data reveals that the mutation of KRAS is found in 44% of CRC patients. In total, 28 genes were identified as differentially expressed genes (DEGs), and the hub genes such as CDKN2A, SPP1, FOS, BCL2L11, and HPSE were verified. Results indicated that key genes (SOX9, SPP1) significant correlation with the target prediction of the active herbal ingredients by molecular docking analysis. Furthermore, KEAP1, NFE2L2, SOX9 expression were decreased significantly with the treatment of potential ingredients. Furthermore, cyclopamine could enhance the sensitivity of HCT116 cells, downregulated the expression of SPP1, and induced activation of KEAP1‐NFE2L2 pathway, which cell death are characteristic features of apoptosis, and enhanced anticancer effect. Therefore, KEAP1‐related genes might be important oncogenic signatures in KRAS mutant CRC cells and cyclopamine was identified as a potential ingredient and regulated the predict targets of SOX9 and SPP1, may be expand the efficacy and range of novel and effective therapeutics.

Abstract Background The EQ-5D-Y is a generic preference-weighted measure for children and adolescents which was developed within Europe. Two versions exist, the EQ-5D-Y-3L (Y-3L) and EQ-5D-Y-5L (Y-5L). This study aimed to cross-culturally adapt the Y-3L and Y-5L for use in Singapore and to assess the content validity, specifically, the relevance and comprehensiveness of the EQ-5D-Y descriptive system (DS) in Asia. Methods To culturally adapt the instruments, an expert panel consisting of paediatricians and primary school educators were consulted. Modifications suggested by the expert panel were tested via cognitive debriefing interviews with children aged 8–12 in Singapore. To assess the content validity of the EQ-5D-Y DS, interviews were conducted with both healthy (n = 8) and ill children (n = 6) aged 8–15. In the interviews, children discussed their experience with poor health and commented on the comprehensiveness and relevance of the EQ-5D-Y DS. Results The cross-cultural adaptation process led to minor modifications to the UK English Y-3L and Y-5L versions, including using phrases familiar to the local children and adding examples to facilitate understanding. The five health dimensions in the EQ-5D-Y DS were spontaneously elicited when children discussed their experience with poor health. All health dimensions related to poor health elicited from the interviews fell into three broad categories: physical health (e.g. Appetite, Mobility, and Sleep), mental well-being (e.g. Annoyed/Frustrated and Scared/Worried), and social relationships (e.g. Family and Friends). The EQ-5D-Y DS was generally found to be relevant and comprehensive, although some health dimensions that may be relevant to the local population (Social relationship and Appetite) were not covered. Conclusions The UK English EQ-5D-Y instruments were adapted to produce the Singapore English EQ-5D-Y instrument that were comprehensible to local children as young as 8 years old. The EQ-5D-Y DS was generally relevant and comprehensive to measure poor health of local children. Future studies should ascertain the benefits of adding bolt-on items related to social relationships and appetite to the EQ-5D-Y DS.

Abstract Deep neural networks have been used to solve Ising models, including autoregressive neural networks, convolutional neural networks, recurrent neural networks, and graph neural networks. Learning probability distributions of energy configuration or finding ground states of disordered, fully connected Ising models is essential for statistical mechanics and NP-hard problems. Despite tremendous efforts, neural network architectures with abilities to high-accurately solve these intractable problems on larger systems remain a challenge. Here we propose a variational autoregressive architecture with a message passing mechanism, which effectively utilizes the interactions between spin variables. The architecture trained under an annealing framework outperforms existing neural network-based methods in solving several prototypical Ising spin Hamiltonians, especially for larger systems at low temperatures. The advantages also come from the great mitigation of mode collapse during training process. Considering these difficult problems to be solved, our method extends computational limits of unsupervised neural networks to solve combinatorial optimization problems.

Given the association of Epstein-Barr virus (EBV) with subjective perception of fatigue and demyelination in clinical conditions, the question about potential subclinical effects in the adult general population remains open. We investigate the association between individuals’ EBV immune response and perceived fatigue in a community dwelling cohort (n = 864, age 62 ± 10 years old; 49% women) while monitoring brain tissue properties. Fatigue levels are assessed with the established fatigue severity scale, the EBNA-1 and VCA p18 immunoglobulin G (IgG) chronic response – with multiplex serology and the estimates of local brain volume, myelin content, and axonal density - using relaxometry- and multi-shell diffusion-based magnetic resonance imaging (MRI). In our analysis we adjust for the effects of demographic and cardiovascular risk factors, sleep apnea, depression, and polygenic risk score for multiple sclerosis. We demonstrate that EBNA-1 IgG levels are positively associated with perceived levels of fatigue, whilst VCA p18 IgG levels show a positive correlation with myelin content and a negative one with an estimate of axonal g-ratio in male participants. In the context of EBVs immune response, the polygenic risk for multiple sclerosis is not associated with increased fatigue levels, brain myelination or atrophy. Our findings bring empirical evidence about the potential role of EBVs chronic immune response in perceived fatigue and hint towards a protective role of myelination specific for men. They underscore the added value of advanced assessment of brain tissue microstructure in uncovering the mechanisms behind frequent fatigue complaints associated with EBV infection and multiple sclerosis.

Hydrochlorothiazide (HCTZ) is a widely utilized diuretic for the treatment of hypertension. The photosensitivity of HCTZ has been recognized for six decades, with UVA being considered the primary culprit. However, the precise molecular mechanism of HCTZ sensitizing skin to UV radiation remains unknown. In this study, we demonstrate that HCTZ exacerbates UVB-induced photosensitivity in normal skin by disrupting the DNA damage response, a crucial network responsible for maintaining epidermal homeostasis. Here, we found that HCTZ aggravates UVB-induced mouse skin damage. Through transcriptomic and proteomic profiling, we have found that the cell cycle and p53 signaling pathway may contribute to the photosensitivity caused by HCTZ. In keratinocytes, HCTZ promotes the transition from G1 to S phase and inhibits the p53 signaling pathway after exposure to UV radiation. We have found that HCTZ enhances the accumulation of DNA damage induced by UVB and impairs nucleotide excision repair (NER), which is responsible for repairing UVB-induced DNA lesions, by inhibiting the expression of NER-related genes and shortening the duration of G1 phase. Furthermore, pharmacologically inducing G1 arrest eliminates HCTZ-induced accumulation of damaged DNA. These findings unveil an unknown mechanism through which HCTZ impairs NER and interferes with UVB-induced cell cycle arrest, ultimately leading to improper response towards DNA damage and increased skin sensitivity.

ObjectiveChronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality, and self-management is a key component for better outcomes of COPD. Recently, nudging has shown promising potential in COPD management. In the present study, we conducted a systematic review to collate the list of nudges and identified the variables that influence nudging.MethodsWe undertook a systematic review. We employed database searches and snowballing. Data from selected studies were extracted. The risk of bias was assessed using the Cochrane Effective Practice and Organization of Care risk of bias tool. The study is registered with PROSPERO, CRD42023427051.ResultsWe retrieved 4,022 studies from database searches and 38 studies were included. By snowballing, 5 additional studies were obtained. Nudges were classified into four types: social influence, gamification, reminder, and feedback. Medication adherence, inhalation technique, physical activity, smoking cessation, vaccination administration, exercise capacity, self-efficacy, pulmonary function, clinical symptoms, and quality of life were analyzed as targeted health behaviors and outcomes. We found medication adherence was significantly improved by reminders via mobile applications or text materials, as well as feedback based on devices. Additionally, reminders through text materials greatly enhance inhalation techniques and vaccination in patients.ConclusionThis review demonstrates nudging can improve the health behaviors of patients with COPD and shows great potential for certain outcomes, particularly medication adherence, inhalation techniques, and vaccination. Additionally, the delivery modes, the patient characteristics, and the durations and seasons of interventions may influence the successful nudge-based intervention.Clinical trial registrationThis review has been registered in the international Prospective Registry of Systematic Evaluation (PROSPERO) database (identifier number CRD42023427051).

Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear. Methods First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients. Results Serological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA β-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD. Conclusion In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications. Graphical Abstract

Abstract Background Antibiotic-associated diarrhea (AAD) can prolong hospitalization, increase medical costs, and even lead to higher mortality rates. Therefore, it is essential to predict the incidence of AAD in elderly intensive care unit(ICU) patients. The objective of this study was to create a prediction model that is both interpretable and generalizable for predicting the incidence of AAD in elderly ICU patients. Methods We retrospectively analyzed data from the First Medical Center of the People’s Liberation Army General Hospital (PLAGH) in China. We utilized the machine learning model Extreme Gradient Boosting (XGBoost) and Shapley’s additive interpretation method to predict the incidence of AAD in elderly ICU patients in an interpretable manner. Results A total of 848 adult ICU patients were eligible for this study. The XGBoost model predicted the incidence of AAD with an area under the receiver operating characteristic curve (ROC) of 0.917, sensitivity of 0.889, specificity of 0.806, accuracy of 0.870, and an F1 score of 0.780. The XGBoost model outperformed the other models, including logistic regression, support vector machine (AUC = 0.809), K-nearest neighbor algorithm (AUC = 0.872), and plain Bayes (AUC = 0.774). Conclusions While the XGBoost model may not excel in absolute performance, it demonstrates superior predictive capabilities compared to other models in forecasting the incidence of AAD in elderly ICU patients categorized based on their characteristics.

Abstract The Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aimed to assess if bacterial genetics governs MTBC pathogenesis or if local co-adaptation translates into differential susceptibility of human macrophages to infection by different MTBC genotypes. We generated macrophages from cryopreserved blood mononuclear cells of Tanzanian tuberculosis patients, from which the infecting MTBC strains had previously been phylogenetically characterized. We infected these macrophages ex vivo with a phylogenetically similar MTBC strain (“matched infection”) or with strains representative of other MTBC lineages (“mismatched infection”). We found that L1 infections resulted in a significantly lower bacterial burden and that the intra-cellular replication rate of L2 strains was significantly higher compared the other MTBC lineages, irrespective of the MTBC lineage originally infecting the patients. Moreover, L4-infected macrophages released significantly greater amounts of TNF-α, IL-6, IL-10, MIP-1β, and IL-1β compared to macrophages infected by all other strains. While our results revealed no measurable effect of local adaptation, they further highlight the strong impact of MTBC phylogenetic diversity on the variable outcome of the host–pathogen interaction in human tuberculosis.

Abstract Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is a medicinal and edible plant with multiple functions of liver protection, anti-tumor, anti-inflammation, balancing blood sugar and blood lipids. The nutritional value of the G. pentaphyllum plant is mainly due to its rich variety of biologically active substances, such as flavonoids, terpenes and polysaccharides. In this study, we performed a comprehensive analysis combining metabolomics and root, stem and leaf transcriptomic data of G. pentaphyllum. We used transcriptomics and metabolomics data to construct a dynamic regulatory network diagram of G. pentaphyllum flavonoids and terpenoids, and screened the transcription factors involved in flavonoids and terpenoids, including basic helix-loop-helix (bHLH), myb-related, WRKY, AP2/ERF. Transcriptome analysis results showed that among the DEGs related to the synthesis of flavonoids and terpenoids, dihydroflavonol 4-reductase (DFR) and geranylgeranyl diphosphate synthases (GGPPS) were core genes. This study presents a dynamic image of gene expression in different tissues of G. pentaphyllum, elucidating the key genes and metabolites of flavonoids and terpenoids. This study is beneficial to a deeper understanding of the medicinal plants of G. pentaphyllum, and also provides a scientific basis for further regulatory mechanisms of plant natural product synthesis pathways and drug development.

Background: The impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in acute myeloid leukemia (AML) is still controversial. The purpose of this study is to explore the impact of rhG-CSF administration on clinical efficacy and immune cell subsets after initial induction chemotherapy in AML. Methods: The clinical efficacy and immune cell subsets were compared in the newly diagnosed patients with AML according to whether rhG-CSF was used after initial induction chemotherapy. Next, rhG-CSF stimulation experiments on leukemia cell lines and primary leukemia blasts were performed in vitro. Results: There was no statistical difference between control group and rhG-CSF therapy group in complete remission rate and relapse free survival. The duration of agranulocytosis was significantly shortened in rhG-CSF therapy group compared with control group. The percentage of circulating monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) were significantly increased after the administration of rhG-CSF. Furthermore, it was found that rhG-CSF did not promote the proliferation of leukemia cell lines and primary leukemia blasts, but increased the proportion of M-MDSCs and Tregs in vitro. Conclusions: Administration of rhG-CSF after initial induction therapy of AML does not affect the clinical remission and relapse rate, but reduces the duration of agranulocytosis and increases the proportion of M-MDSCs and Tregs. [ABSTRACT FROM AUTHOR]

As an aircraft or spacecraft ascends, the atmospheric pressure drops. If the internal pressure is not released, a pressure differential develops on the facesheet. With an in-plane load from vehicle acceleration as well, the pressure and in-plane load may cause failure. Vented sandwich structures are strongly preferred since they release the internal pressure; however, special cases still require an unvented design. This paper provides an analysis and test methodology for unvented sandwich structures. Parametric studies of facesheet-core debonding and buckling were conducted via finite element analysis, considering geometric, material, and load parameters. Design curves based on the key nondimensional parameters were tuned to the data from the parametric study, providing a tool to predict facesheet-core debond failure. Examples of how to use the design curves in practical applications are provided. [ABSTRACT FROM AUTHOR]