Which intervention is optimal to control blood glucose and improve physical performance in the elderly living with type 2 diabetes mellitus? A network meta-analysis.

BACKGROUND AND OBJECTIVES: This study aimed to find the optimal intervention available to both control blood glucose and improve physical function in the geriatric population with T2DM. METHODS AND STUDY DESIGN: A systemic review and network meta-analysis (NMA) was conducted to assess and rank the comparative efficacy of different interventions on glycosylated hemoglobin A1c (HbAc1), fasting blood glucose (FBG), muscle mass, grip strength, gait speed, lower body muscle strength, and dynamic balance. A total of eight databases were searched for eligible randomized controlled trials (RCTs) that the elderly aged more than 60 years or with mean age ≥ 55 years, the minimal duration of the RCT intervention was 6 weeks, and those lacking data about glycemic level and at least one indicator of physical performance were excluded. The Cochrane risk of bias tool was used to assess the bias of each study included. Bayesian NMA was performed as the main results, the Bayesian meta regression and the frequentist NMA as sensitivity analysis. RESULTS: Of the 2266 literature retrieved, 27 RCTs with a total of 2289 older adults were included. Health management provided by health workers exerts beneficial effects that is superior to other interventions at achieving glycemic control, but less marked improvement in physical performance. Exercise combined with cognitive training showed more pronounced improvement in muscle strength, gait speed, and dynamic balance, but ranked behind in decreasing the HbAc1 and FBG. CONCLUSIONS: Personalized health management combined with physical and cognitive training might be the optimal intervention to both accomplish glycemic control and improvement of physical performance. Further RCTs are needed to validate and assess the confidence of our results from this NMA.

Memantine alleviates cognitive impairment and hippocampal morphology injury in a mouse model of chronic alcohol exposure.

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol abuse and dependence. The pathophysiology of ARCI, pivotal for refined therapeutic approaches, is not fully elucidated, posing a risk of progression to severe neurological sequelae such as Korsakoff's syndrome (KS) and Alcohol-Related Dementia (ARD). This study ventures into the underlying mechanisms of chronic alcohol-induced neurotoxicity, notably glutamate excitotoxicity and cytoskeletal disruption, and explores the therapeutic potential of Memantine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor known for its neuroprotective effect against excitotoxicity. Our investigation centers on the efficacy of Memantine in mitigating chronic alcohol-induced cognitive and hippocampal damages in vivo. Male C57BL/6J mice were subjected to 30 % (v/v, 6.0 g/kg) ethanol via intragastric administration alongside Memantine co-treatment (10 mg/kg/day, intraperitoneally) for six weeks. The assessment involved Y maze, Morris water maze, and novel object recognition tests to evaluate spatial and recognition memory deficits. Histopathological evaluations of the hippocampus were conducted to examine the extent of alcohol-induced morphological changes and the potential protective effect of Memantine. The findings reveal that Memantine significantly improves chronic alcohol-compromised cognitive functions and mitigates hippocampal pathological changes, implicating a moderating effect on the disassembly of actin cytoskeleton and microtubules in the hippocampus, induced by chronic alcohol exposure. Our results underscore Memantine's capability to attenuate chronic alcohol-induced cognitive and hippocampal morphological harm may partly through regulating cytoskeleton dynamics, offering valuable insights into innovative therapeutic strategies for ARCI.

Advancing Precise Syphilis Diagnosis: A Nontreponemal IgM Antibody-Based Model for Latent Syphilis Staging.

Purpose: Accurate differentiation between early and late latent syphilis stages is pivotal for patient management and treatment strategies. Nontreponemal IgM antibodies have shown potential in discriminating latent syphilis staging by differentiating syphilis activity. This study aimed to develop a predictive nomogram model for latent syphilis staging based on nontreponemal IgM antibodies. Patients and Methods: We explored the correlation between nontreponemal IgM antibodies and latent syphilis staging and developed a nomogram model to predict latent syphilis staging based on 352 latent syphilis patients. Model performance was assessed using AUC, calibration curve, Hosmer-Lemeshow χ2 statistics, C-index, Brier score, decision curve analysis, and clinical impact curve. Additionally, an external validation set was used to further assess the model's stability. Results: Nontreponemal IgM antibodies correlated with latent syphilis staging. The constructed model demonstrated a strong discriminative capability with an AUC of 0.743. The calibration curve displayed a strong fit, key statistics including Hosmer-Lemeshow χ² at 2.440 (P=0.486), a C-index score of 0.743, and a Brier score of 0.054, all suggesting favorable model calibration performance. Decision curve analysis and clinical impact curve highlighted the model's robust clinical applicability. The external validation set yielded an AUC of 0.776, Hosmer-Lemeshow χ² statistics of 2.440 (P=0.486), a C-index score of 0.767, and a Brier score of 0.054, further underscored the reliability of the model. Conclusion: The nontreponemal IgM antibody-based predicted model could equip clinicians with a valuable tool for the precise staging of latent syphilis and enhancing clinical decision-making.

Patient compliance to sublingual immunotherapy for mite-induced allergic rhinitis: A retrospective study.

Background: Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment. Objective: To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance. Methods: The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the pre-pandemic period. Results: Of 3117 patients, 507 (16.27%) patients (ages, 5-67 years) were identified as non-compliant. The most common reason for non-compliance was poor efficacy (27.22%). The non-compliance rate was highest during 24-36 months of SLIT (28.13%, 153/544), followed by 12-24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P = 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3-6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis. Conclusions: The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.

Differentially Expressed Proteins in the Serum of Elderly Patients Who Experienced Perioperative Neurocognitive Disorders Following Transurethral Resection of the Prostate.

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. METHODS: A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. RESULTS: Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. CONCLUSION: The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. CLINICAL TRIAL REGISTRATION: Registered (ChiCTR2000028836). Date (20190306).

Effects of high-intensity ultrasound on physicochemical and gel properties of myofibrillar proteins from the bay scallop (Argopecten irradians).

Myofibrillar proteins (MPs) have a notable impact on the firmness and flexibility of gel-based products. Therefore, enhancing the gelation and emulsification properties of scallop MPs is of paramount significance for producing high-quality scallop surimi products. In this study, we investigated the effects of high-intensity ultrasound on the physicochemical and gelation properties of MPs from bay scallops (Argopecten irradians). The carbonyl content of MPs significantly increased with an increase in ultrasound power (150, 350, and 550 W), indicating ultrasound-induced MP oxidation. Meanwhile, high-intensity ultrasound treatment (550 W) enhanced the emulsifying capacity and the short-term stability of MPs (up to 72.05 m2/g and 153.05 min, respectively). As the ultrasound power increased, the disulfide bond content and surface hydrophobicity of MPs exhibited a notable increase, indicating conformational changes in MPs. Moreover, in the secondary structure of MPs, the α-helix content significantly decreased, whereas the ß-sheet content increased, thereby suggesting the ultrasound-induced stretching and flexibility of MP molecules. Sodium-dodecyl sulfate-polyacrylamide gel electrophoresis and scanning electron microscopy analysis further elucidated that high-intensity ultrasound induced MP oxidation, leading to modification of amino acid side chains, intra- and intermolecular cross-linking, and MP aggregation. Consequently, high-intensity ultrasound treatment was found to augment the viscoelasticity, gel strength, and water-holding capacity of MP gels, because ultrasound treatment facilitated the formation of a stable network structure in protein gels. Thus, this study offers theoretical insights into the functional modification of bay scallop MPs and the processing of its surimi products.

[Effects of Different Proportions of Ammonium Sulfate Replacing Urea on Soil Nutrients and Rhizosphere Microbial Communities].

In order to investigate the effects of ammonium sulfate, an industrial by-product, on soil nutrients and microbial community when applied in different proportions instead of using urea as nitrogen fertilizer, a pot corn experiment was conducted. A completely randomized block experimental design was used, with a total of five treatments:CK (no fertilization), U10S0 (100 % urea), U8S2 (80 % urea + 20 % ammonium sulfate), U6S4(60 % urea + 40 % ammonium sulfate), and U0S10 (100 % ammonium sulfate). The basic physical and chemical properties of soil and the dry weight of maize plants were determined by conventional methods, and microbial sequencing was performed using the Illumina NovaSeq platform. The experiment results showed that:① In each growth stage of maize, the pH of soil treated with fertilization (7.85-8.15) was decreased compared with that of CK (8.1-8.21), and the pH showed a decreasing trend with the increase in ammonium sulfate content. ② The soil available nitrogen content increased gradually with the increase in the ammonium sulfate ratio at each growth stage of maize. Compared with that in the CK and U10S0 treatments, the ratio in the U0S10 treatment increased 30.56 % to 63.68 % and 13.22 % to 38.43 %, respectively. The variation trend of organic carbon content was opposite to that of available nitrogen (U8S2 > U6S4 > U0S10), and the addition of ammonium sulfate was still higher than that of U10S0 at other growth stages except for the seedling stage. ③ The protease activity of all fertilization treatments was higher than that of the control, and the protease activity was gradually enhanced with the continuous growth of corn and the increase in the ammonium sulfate ratio. The protease activity of the U0S10 treatment was higher than that of the U10S0 treatment at each growth stage of corn, which increased by 10.54 %-100 %. Soil sucrase activity ranged from 0.04 to 0.24 mg·(g·24 h)-1, and those in the U0S10 treatments were significantly higher than those in the U10S0 and CK treatments at all growth stages, increasing by 20.32 % to 99.16 % and 24.31 % to 79.33 %, respectively. ④ The species abundance of bacteria and fungi in maize rhizosphere under all fertilization treatments were lower than those under the CK treatment, followed by those under the U10S0 treatment. The species diversity trend of the bacterial community in the three treatments with ammonium sulfate replacing urea were U8S2 > U0S10 > U6S4, and that of fungi were U6S4 > U8S2 > U0S10. ⑤ The maize dry weight of the U10S0 treatment and U0S10 treatment was the highest, which was 39.47 % and 36.16 % higher than that of the CK treatment, respectively, but the difference was not significant. The Pearson model showed that the species abundance and diversity of soil rhizosphere fungi and bacteria were affected by relevant environmental variables, among which pH value and soil available nitrogen content were the most important factors affecting microbial diversity. In conclusion, when corn planting in calcareous brown soil, replacing urea with a certain proportion of ammonium sulfate can improve soil nutrients more than urea alone, which affects the growth and rhizosphere microbial community of corn to a certain extent and has a greater yield.

Beyond Immune Balance: The Pivotal Role of Decidual Regulatory T Cells in Unexplained Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive pregnancy failures, which brings tremendous stress to women of childbearing age and seriously affects family well-being. However, the reason in about 50% of cases remains unknown and is defined as unexplained recurrent spontaneous abortion (URSA). The immunological perspective in URSA has attracted widespread attention in recent years. The embryo is regarded as a semi-allogeneic graft to the mother. A successful pregnancy requires transition to an immune environment conducive to embryo survival at the maternal-fetal interface. As an important member of regulatory immunity, regulatory T (Treg) cells play a key role in regulating immune tolerance at the maternal-fetal interface. This review will focus on the phenotypic plasticity and lineage stability of Treg cells to illustrate its relationship with URSA.

Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality.

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

Functional analysis of CYP71AV1 reveals the evolutionary landscape of artemisinin biosynthesis.

Artemisinin biosynthesis, unique to Artemisia annua, is suggested to have evolved from the ancestral costunolide biosynthetic pathway commonly found in the Asteraceae family. However, the evolutionary landscape of this process is not fully understood. The first oxidase in artemisinin biosynthesis, CYP71AV1, also known as amorpha-4,11-diene oxidase (AMO), has specialized from ancestral germacrene A oxidases (GAOs). Unlike GAO, which exhibits catalytic promiscuity toward amorpha-4,11-diene, the natural substrate of AMO, AMO has lost its ancestral activity on germacrene A. Previous studies have suggested that the loss of the GAO copy in A. annua is responsible for the abolishment of the costunolide pathway. In the genome of A. annua, there are two copies of AMO, each of which has been reported to be responsible for the different product profiles of high- and low-artemisinin production chemotypes. Through analysis of their tissue-specific expression and comparison of their sequences with those of other GAOs, it was discovered that one copy of AMO (AMOHAP) exhibits a different transcript compared to the reported artemisinin biosynthetic genes and shows more sequence similarity to other GAOs in the catalytic regions. Furthermore, in a subsequent in vitro enzymatic assay, the recombinant protein of AMOHAP unequivocally demonstrated GAO activity. This result clearly indicates that AMOHAP is a GAO rather than an AMO and that its promiscuous activity on amorpha-4,11-diene has led to its misidentification as an AMO in previous studies. In addition, the divergent expression pattern of AMOHAP compared to that of the upstream germacrene A synthase may have contributed to the abolishment of costunolide biosynthesis in A. annua. Our findings reveal a complex evolutionary landscape in which the emergence of a new metabolic pathway replaces an ancestral one.

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

Single-cell insights: pioneering an integrated atlas of chromatin accessibility and transcriptomic landscapes in diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM's unique cell states and molecular landscape for targeted therapeutic interventions. METHODS: Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings. RESULTS: This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation. CONCLUSION: Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.

Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.

BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

Association between triglyceride-glucose index and colorectal polyps: A retrospective cross-sectional study.

BACKGROUND: Colorectal polyps (CPs) are frequently occurring abnormal growths in the colorectum, and are a primary precursor of colorectal cancer (CRC). The triglyceride-glucose (TyG) index is a novel marker that assesses metabolic health and insulin resistance, and has been linked to gastrointestinal cancers. AIM: To investigate the potential association between the TyG index and CPs, as the relation between them has not been documented. METHODS: A total of 2537 persons undergoing a routine health physical examination and colonoscopy at The First People's Hospital of Kunshan, Jiangsu Province, China, between January 2020 and December 2022 were included in this retrospective cross-sectional study. After excluding individuals who did not meet the eligibility criteria, descriptive statistics were used to compare characteristics between patients with and without CPs. Logistic regression analyses were conducted to determine the associations between the TyG index and the prevalence of CPs. The TyG index was calculated using the following formula: Ln [triglyceride (mg/dL) × glucose (mg/dL)/2]. The presence and types of CPs was determined based on data from colonoscopy reports and pathology reports. RESULTS: A nonlinear relation between the TyG index and the prevalence of CPs was identified, and exhibited a curvilinear pattern with a cut-off point of 2.31. A significant association was observed before the turning point, with an odds ratio (95% confidence interval) of 1.70 (1.40, 2.06), P < 0.0001. However, the association between the TyG index and CPs was not significant after the cut-off point, with an odds ratio (95% confidence interval) of 0.57 (0.27, 1.23), P = 0.1521. CONCLUSION: Our study revealed a curvilinear association between the TyG index and CPs in Chinese individuals, suggesting its potential utility in developing colonoscopy screening strategies for preventing CRC.

Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS: The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.

Predicting risk of preterm birth in singleton pregnancies using machine learning algorithms.

We aimed to develop, train, and validate machine learning models for predicting preterm birth (<37 weeks' gestation) in singleton pregnancies at different gestational intervals. Models were developed based on complete data from 22,603 singleton pregnancies from a prospective population-based cohort study that was conducted in 51 midwifery clinics and hospitals in Wenzhou City of China between 2014 and 2016. We applied Catboost, Random Forest, Stacked Model, Deep Neural Networks (DNN), and Support Vector Machine (SVM) algorithms, as well as logistic regression, to conduct feature selection and predictive modeling. Feature selection was implemented based on permutation-based feature importance lists derived from the machine learning models including all features, using a balanced training data set. To develop prediction models, the top 10%, 25%, and 50% most important predictive features were selected. Prediction models were developed with the training data set with 5-fold cross-validation for internal validation. Model performance was assessed using area under the receiver operating curve (AUC) values. The CatBoost-based prediction model after 26 weeks' gestation performed best with an AUC value of 0.70 (0.67, 0.73), accuracy of 0.81, sensitivity of 0.47, and specificity of 0.83. Number of antenatal care visits before 24 weeks' gestation, aspartate aminotransferase level at registration, symphysis fundal height, maternal weight, abdominal circumference, and blood pressure emerged as strong predictors after 26 completed weeks. The application of machine learning on pregnancy surveillance data is a promising approach to predict preterm birth and we identified several modifiable antenatal predictors.

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening.

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study.

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Fluctuating light induces a significant photoinhibition of photosystem I in maize.

In nature, light intensity usually fluctuates and a sudden shade-sun transition can induce photodamage to photosystem I (PSI) in many angiosperms. Photosynthetic regulation in fluctuating light (FL) has been studied extensively in C3 plants; however, little is known about how C4 plants cope FL to prevent PSI photoinhibition. We here compared photosynthetic responses to FL between maize (Zea mays, C4) and tomato (Solanum lycopersicum, C3) grown under full sunlight. Maize leaves had significantly higher cyclic electron flow (CEF) activity and lower photorespiration activity than tomato. Upon a sudden shade-sun transition, maize showed a significant stronger transient PSI over-reduction than tomato, resulting in a significant greater PSI photoinhibition in maize after FL treatment. During the first seconds upon shade-sun transition, CEF was stimulated in maize at a much higher extent than tomato, favoring the rapid formation of trans-thylakoid proton gradient (ΔpH), which was helped by a transient down-regulation of chloroplast ATP synthase activity. Therefore, modulation of ΔpH by regulation of CEF and chloroplast ATP synthase adjusted PSI redox state at donor side, which partially compensated for the deficiency of photorespiration. We propose that C4 plants use different photosynthetic strategies for coping with FL as compared with C3 plants.

The effect of vitamin K supplementation on cardiovascular risk factors: a systematic review and meta-analysis.

Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is necessary because of the increased mortality risk of that. The aim of our meta-analysis is to reveal the general effect of vitamin K supplementation on its related risk factors. Original databases were searched using standard keywords to identify all randomized clinical trials (RCTs) investigating the effects of vitamin K on CVD. Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes. The statistical heterogeneity was determined using the Cochran's Q test and I2 statistics. Seventeen studies were included in this systematic review and meta-analysis. The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: -0⋅24, 95 % CI: -0⋅49, -0⋅02, P = 0⋅047) significantly compared to the placebo group. However, no significant effect was observed on other outcomes. Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR. However, no significant effect was observed on other variables. Also, subgroup analysis showed no potential effect of vitamin K supplementation on any outcome and omitting any articles did not affect the final results. We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.