bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketogenic diet in treating sepsis-related acquired weakness: is it friend or foe?
Authors: Miao Yanmei , Xie Leiyu , Chen Shaolin , Zhang Xiaoming , Liu Wenjie , Xie Peng 
Published: November 2024

BackgroundSepsis is the body’s extreme response to an infection leading to organ dysfunction. Sepsis-related acquired weakness (SAW), a critical illness closely related to metabolic disorders, is characterized by generalized sepsis-induced skeletal muscle weakness, mainly manifesting as symmetrical atrophy of respiratory and limb muscles. Muscle accounts for 40% of the body’s total mass and is one of the major sites of glucose and energy absorption. Diet affects skeletal muscle metabolism, which further impacts physiology and signaling pathways. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has shown benefits in patients with a variety of neuromuscular disorders. Patients with SAW are in a hypermetabolic state and can consume approximately 1% of total body muscle mass in a day. Due to the decreased total body energy expenditure secondary to starvation, skeletal muscles enter a low metabolic state, with reduced gluconeogenesis and protein consumption and elevated levels of ketone bodies. The latest research suggests that KD may be a new strategy for SAW prevention and treatment, but its mechanism is still unclear.ObjectiveOur article aims to explore the effect and mechanism of KD on SAW. And we hope that our review will inspire further research on the KD and foster the exploration of novel strategies for combating SAW.MethodsSearch medical databases and related academic websites, using keywords such as “Sepsis-related acquired weakness,” “ketogenic diet,” and “skeletal muscle,” and select representative literature. Using the method of induction and summary, analyze the effect and mechanism of KD on SAW.ResultsCompared with early nutrition, KD has a more protective effect on SAW, but its mechanism is complex. Firstly, KD can alter energy metabolism substrates to affect SAW’s energy metabolism; Secondly, KD can directly act as a signaling molecule to improve mitochondrial function in skeletal muscle and stimulate skeletal muscle regeneration signaling molecules; Thirdly, KD can affect the gut microbiota to exert anti-inflammatory effects, enhance immunity, and thus protect SAW.ConclusionKD has a protective effect on SAW, which includes improving energy metabolism, stimulating muscle regeneration signals, optimizing gut microbiota composition, and reducing inflammation and oxidative stress.
Comparative analysis of six nutritional scores in predicting prognosis of COVID-19 patients
Authors: Zou Shangpu , Lin Pengcheng , Chen Xiaoyu , Xia Lijing , Liu Xiling , Su Shanshan , Zhou Ying , Li Yuping 
Published: November 2024

BackgroundIdentifying nutritional risk in COVID-19 patients poses a challenge due to the unique qualities of every nutritional screening instrument. The objective was to assess the efficacy of six nutritional scores, including the Nutritional Risk Screening 2002 (NRS-2002) score, the NUTRIC (nutrition risk in the critically ill) score, the modified NUTRIC score, the prognostic nutritional index (PNI), controlling nutritional status (CONUT) score, TCB index (TCBI), predicting prognosis of COVID-19 patients.MethodsClinical data were collected from COVID-19 patients admitted to the First Affiliated Hospital of Wenzhou Medical University between December 2022 and February 2023. Participants in this research were divided into two groups: all patients and those specifically from the intensive care unit (ICU). Each group was further stratified into two groups: survivors and non-survivors.Result506 COVID-19 patients and 190 COVID-19 patients in intensive care unit (ICU) were evaluated. In all COVID-19 patients, we found that NRS-2002 (p &lt; 0.001) and TCBI (p = 0.002) were statistically significant independent predictors in multivariate analyses, while APACHE II score (p = 0,048) and the mNUTRIC score (p = 0.025) were statistically significant independent predictors in multivariate analyses in ICU patients. The NRS-2002 demonstrated a higher AUC value (0.687) than other nutritional scores in all patients, with an optimum cut-off value of 3, translating into a corresponding sensitivity of 66.2% and specificity of 68.7%. With an optimum cut-off value of 4, the mNUTRIC score demonstrated a higher AUC value (0.884) in ICU patients, resulting in a sensitivity of 88.4% and a specificity of 76.9%. By using the discrimination and clinical application (DCA) curve, NRS-2002 demonstrated the greatest net benefit in all patients, while NUTRIC score and mNUTRIC score offered the more significant overall advantage than other nutritional scores in ICU patients. Kaplan–Meier analyses showed lower survival rates in patients in low nutritional risk.ConclusionMalnutrition was common in COVID-19 patients. The mNUTRIC score and NRS-2002 were, respectively, more effctive scoring systems of prognosis in all COVID-19 patients and severe or critical COVID-19 patients of the intensive care unit (ICU).
Negative response to immunotherapy in dMMR or MSI-H gastric cancer with APC and PTEN mutations: a case report
Authors: Liu Jiang , Zhang Xiumei , Ren Qun , Song Chuanjun , Yu Jianhe , Cai Yin , Chen Dadong 
Published: November 2024

BackgroundMicrosatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) represents a distinct molecular phenotype observed in malignant tumors. These tumors typically exhibit high levels of programmed cell death 1 ligand 1 (PD-L1) expression and high tumor mutational burden (TMB), resulting in an enhanced response to immune checkpoint inhibitors (ICI) therapy. The emergence of ICI has transformed the therapeutic strategy of gastric cancer (GC). Immune checkpoint blockade significantly improves the survival of gastric cancer patients, especially those with MSI-H or dMMR. However, it’s worth noting that not all patients with MSI-H respond favorably to this treatment. It has been reported that factors such as tumor heterogeneity, alterations in the tumor microenvironment, and aberrant activation of tumor-related signaling pathways have been linked with resistance to ICI therapy.Case presentationHere, we describe a case of dMMR and MSI-H GC with adenomatous polyposis coli (APC) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) mutations that failed to respond to anti-PD-1 combined with anti-HER2 (human epidermal growth factor receptor-2) therapy and chemotherapy. We attempted to elucidate the underlying causes and mechanisms behind this lack of response, and to provide new insights into treatment options for these patients.ConclusionsMutations of key genes within tumor-related signaling pathways and the infiltration of CD8+T cells in the tumor microenvironment may influence the efficacy of immunotherapy for MSI-H solid tumors.
Lactylation-related gene signature accurately predicts prognosis and immunotherapy response in gastric cancer
Authors: Sun Xuezeng , Dong Haifeng , Su Rishun , Chen Jingyao , Li Wenchao , Yin Songcheng , Zhang Changhua 
Published: November 2024

BackgroundGastric cancer (GC) is a malignant tumor associated with significant rates of morbidity and mortality. Hence, developing efficient predictive models and directing clinical interventions in GC is crucial. Lactylation of proteins is detected in gastric cancer tumors and is linked to the advancement of gastric cancer.MethodsThe The Cancer Genome Atlas (TCGA) was utilized to analyze the gene expression levels associated with lactylation. A genetic pattern linked to lactylation was created using Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. The predictive ability of the model was evaluated and confirmed in the Gene Expression Omnibus (GEO) cohort, where patients were divided into two risk groups based on their scores. The study examined the relationship between gene expression and the presence of immune cells in the context of immunotherapy treatment. In vitro cytotoxicity assays, ELISA and PD-1 and PD-L1interaction assays were used to assess the expression of PD-L1 while knocking down SLC16A7.Results29 predictive lactylation-related genes with differential expression were discovered. A signature consisting of three genes was developed and confirmed. Patients who had higher risk scores experienced worse clinical results. The group with lower risk showed increased Tumor Immune Dysfunction and Exclusion (TIDE) score and greater responsiveness to immunotherapy. The tumor tissues secrete more lactate acid than normal tissues and express more PD-L1 than normal tissues, that is, lactate acid promotes the immune evasion of tumor cells. In GC, the lactylation-related signature showed strong predictive accuracy. Utilizing both anti-lactylation and anti-PD-L1 may prove to be an effective approach for treating GC in clinical settings. We further proved that one of the lactate metabolism related genes, SCL16A7 could promote the expression of PD-L1 in GC cells.ConclusionThe risk model not only provides a basis for better prognosis in GC patients, but also is a potential prognostic indicator to distinguish the molecular and immune characteristics, and the response from Immune checkpoint inhibitors (ICI) therapy and chemotherapy in GC.
Risk association model for atelectasis complication in Mycoplasma pneumoniae pneumonia patients following standardized treatment
Authors: Xu Mingyi , Fan Minhao , Wang Huixia , Qian Jun , Jiang Yi , Zhu Yifan , Zhao Deyu , Liu Feng , Guo Yun , Li Ling 
Published: November 2024

BackgroundMycoplasma pneumoniae pneumonia (MPP) is a common disease of childhood pneumonia, and atelectasis is a serious comorbidity. Traditional diagnostic methods for MPP are limited by low accuracy, emphasizing the need for improved diagnostic approaches. This study aimed to establish a predictive scoring model for early detection of MPP complicated with atelectasis following standardized treatment.MethodsA total of 572 children were retrospectively enrolled, including 40 patients with MPP complicated by atelectasis despite standardized treatment and 532 patients in the non-atelectasis group. Clinical, laboratory, and imaging data within 24 h of admission were collected, including demographic information and various biomarkers. Multivariate logistic regression analysis was employed to identify risk factors and construct a predictive model, evaluated using receiver operating characteristic (ROC) curve analysis.ResultsSignificant differences were observed between the MPP complicated with atelectasis group and the non-atelectasis group in terms of age, hospital admission time, fever duration, neutrophil percentage and count, CRP, ALT, and LDH levels (P &lt; 0.05). According to the multivariate logistic regression analysis, length of fever, neutrophil ratio, platelet count, ALT, LDH, age were incorporated into the nomogram. The predictive model exhibited a sensitivity of 87.97% and specificity of 77.50% according to the ROC curve.ConclusionOur study presents a preliminary risk association model incorporating clinical indicators such as fever duration, neutrophil ratio, platelet count, ALT value, LDH value, and age to aid in the early prediction of atelectasis in children with MPP. Given the methodological limitations, the generalizability of our findings is constrained, and this model should be viewed as an initial framework for clinical assessment rather than a definitive tool.
Congenital intrahepatic portosystemic shunt in 27 children: an experience and treatment strategy of a single centre in China
Authors: Zhang Jin-Shan 
Published: November 2024

ObjectiveTo evaluate treatment strategies for congenital intrahepatic portosystemic shunt (CIPSS) based on the experience of treating 27 children.MethodsBetween August 2017 and January 2024, our team treated 27 children with CIPSS. Twelve patients underwent surgical ligation of the portosystemic shunt, while 15 patients diagnosed prenatally received conservative treatment without surgery. All patients were followed up after diagnosis or surgery. During follow-up, blood ammonia and biochemistry tests, along with ultrasound examinations, were conducted. Clinical presentations were recorded.ResultsThe prenatal diagnosis rate for CIPSS using ultrasound was 74.1% (20/27). Hyperammonemia was the most common clinical manifestation, occurring in 81.5% (22/27) of cases. Jaundice and abnormal liver function were the next most frequent presentations in patients with prenatal diagnosis, with incidences of 80% (16/20) and 65% (13/20), respectively. In 12 patients undergoing surgical ligation, blood ammonia levels returned to normal, the abnormal shunt disappeared as confirmed by ultrasound and CT, and no patients developed portal vein thrombosis or portal hypertension postoperatively. In 15 patients receiving conservative treatment, 53.3% (8/15) experienced spontaneous closure of the abnormal shunt within 1–7 months (median: 3 months). Jaundice and hyperammonemia were completely resolved within 1–8 months in patients receiving conservative treatment.ConclusionCIPSS is a curable congenital anomaly. Prenatal ultrasound is effective for detection. Conservative treatment is recommended until the age of one, followed by surgical ligation or interventional treatment for patients with persistent shunts after 1 year.
Multi-omics insights into beagle dog fed with a sucking-rewarded automatic feeding device
Authors: Jiao Yang , Wang Xin , Yu Aizhen , Wu Li , Li Hongping 
Published: November 2024

BackgroundFacilitating the development of the sucking function in early stages of preterm infants holds substantial potential for influencing their long-term outcomes. To this end, our team has devised a sucking-rewarded automatic feeding device specifically tailored for preterm infants. The present study is designed to investigate the impacts of this innovative device, utilizing a multi-omics profiling approach, on beagle dogs as a surrogate model.MethodsThis study involved seven-day-old male newborn beagle puppies, carefully selected and matched in terms of body weights. The participants were stratified into two groups: the experimental group (AFG, sucking-rewarded feeding group) and the control group (PFG). After a 14-day intervention period, fecal and blood samples were systematically collected from each dog. The collected samples were then subjected to distinct profiling analyses, encompassing the assessment of gut microbial composition, plasma metabolic profiles, and proteomic expression profiles.ResultsThe gut microbial data showed a significant difference between the AFG and PFG groups based on Bray-Curtis dissimilarity (P = 0.048), and the relative abundance of Lactobacillus was significantly more abundant in the AFG group compared to the PFG group. The significantly different metabolites between the two groups were enriched in functional metabolic pathways related to amino acids, fatty acid metabolism, and the nervous system. Notably, neurotransmitter L-glutamic acid was significantly up-regulated in the AFG group. Moreover, the significantly different proteins between the two groups were enriched in GO terms related to oxygen transport, oxygen binding, iron ion binding, hemoglobin complex, and heme binding. Among them, proteins A0A8C0MTD2, P60524, P60529 were significantly up-regulated in the AFG group. Notably, Lactobacillus, L-glutamic acid, A0A8C0MTD2, P60524, and P60529 were correlated with each other through correlation analysis, these molecules play important roles in the neural function and neurodevelopment.ConclusionOur investigation elucidated discernible modifications in gut microbial composition, plasma metabolic profiles, and proteomic expression patterns in beagle dogs subjected to the sucking-rewarded automatic feeding device.
Integration of genomics, clinical characteristics and baseline biological profiles to predict the risk of liver injury induced by high-dose methotrexate
Authors: Lin Chenquan , Ma Rui , Zeng Xiao , Zhang Bikui , Cao Ting , Jiao Shimeng , Chen Hui , He Yifang , Liu Mouze , Cai Hualin 
Published: November 2024

BackgroundHigh-dose methotrexate (HD-MTX) is commonly employed in the treatment of malignant tumors in children and young adults due to its distinctive therapeutic efficacy. Nonetheless, the systemic exposure to MTX often results in liver injury (drug induced liver injury, DILI), thereby imposing limitations on the sustained administration of HD-MTX. Additionally, individual variations including genetic underpinnings attributable to disparities in therapeutic effects and clinical toxicity remain to be elucidated.MethodsA total of 374 patients receiving initial HD-MTX treatment were selected for this study, which aimed to establish a predictive model using binary logistic regression and a visual nomogram for DILI risk assessment. Demographic and clinical characteristics were collected at baseline and post-HD-MTX to explore their correlations with the occurrence of DILI. Additionally, genotyping of 25 single nucleotide polymorphisms from drug transporters and enzymes in the folic acid cycle was performed.ResultG allele mutation in ABCB1 rs1128503, *1b/*1b and *1b/*15 haplotypic mutation in SLCO1B1, female gender, and MTX dosage were identified as independent factors for moderate/severe DILI. Patients with GA or AA genotype in ABCB1 rs1128503 showed significant higher 24h MTX concentration than GG, and those with *1b/*1b haplotype group in SLCO1B1 exhibited lower dose adjusted concentration (C/D) than *1a/*1a group. Besides, patient administrated with HD-MTX were more prevalent to have higher C/D levels when using intravenous plus triple intrathecal injection route than those who were using intravenous injection alone. The composite predictive model (ROC curve: AUC = 0.805), comprising above four factors and 24h MTX concentration, exhibited high accuracy.ConclusionFemale gender, recessive mutation in ABCB1 rs1128503, and a range of MTX concentration may be risk factors for increased susceptibility to DILI. Conversely, the *1b/*1b and *1b/*15 mutations in SLCO1B1 may have a protective effect against DILI. The proposed predictive model facilitates early individual risk assessment, enabling the implementation of proactive prevention strategies.
Cepharanthine as an effective small cell lung cancer inhibitor: integrated insights from network pharmacology, RNA sequencing, and experimental validation
Authors: Zhao Fengyun , Ding Zhaowei , Chen Mengting , Ji Mingfang , Li Fugui 
Published: November 2024

BackgroundSmall cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options and poor prognosis, underscoring the need for new therapeutic agents.MethodsA library of 640 natural products was screened for anti-proliferative activity in SCLC cells. The effects of Cepharanthine (CE) on SCLC cells were assessed in vitro and in vivo. Network pharmacology and RNA sequencing (RNA-seq) were used to elucidate the molecular mechanisms. Pathway enrichment analysis was performed using Gene Set Enrichment Analysis (GSEA) with Hallmark and Reactome gene sets. Protein-protein interaction (PPI) networks, along with the Cytoscape cytoHubba plugin, were used to identify key hub genes. RT-PCR and Western blotting were employed to validate mRNA and protein expression. Molecular docking studies assessed the binding affinity of CE to potential targets. Bioinformatics analyses, including expression profiling, prognostic evaluation, and loss-of-function studies, were used to explore the role of specific genes in SCLC.ResultsCE was identified as a promising SCLC inhibitor. In vitro, CE significantly inhibited SCLC cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. In vivo, CE treatment notably reduced tumor volume in xenograft models. Network pharmacology identified 60 potential target genes, with enrichment analysis indicating their involvement in cholesterol metabolism regulation. RNA-seq and experimental validation further confirmed that CE inhibits cholesterol synthesis in SCLC cells by downregulating key enzymes, including HMGCR, HMGCS1, IDI1, FDFT1, and SQLE. Molecular docking studies confirmed the binding of CE to these enzymes. Additionally, these enzymes were found to be highly expressed in SCLC cells, with elevated levels of HMGCS1, HMGCR, and IDI1 correlating with poor prognosis. Functional assays revealed that silencing these genes significantly suppressed SCLC cell proliferation.ConclusionThis study identifies CE as a potential therapeutic agent for SCLC, acting through the suppression of cholesterol synthesis, and uncovers novel therapeutic targets for the treatment of this aggressive cancer.
Bidirectional relationship between pain and sleep disturbance in middle-aged and older adults: evidence from the China health and retirement longitudinal study
Authors: Yi Duan , Yang Mingyuan , Luo Qipeng , Li Hong , Kong Liang , Cheng Qinghao 
Published: November 2024

BackgroundPain is one of the most prevalent symptoms that disrupt daily functioning and has been increasing in prevalence. Sleep disturbances frequently occur in individuals with pain, making it difficult to initiate and maintain sleep. This study aims to examine the bidirectional correlation between pain and sleep quality/duration among middle-aged and older Chinese adultsParticipants and settingThis study analyzed data from individuals aged 45 years and above who participated in both the 2018 and 2020 baseline surveys of China Health and Retirement Longitudinal Study (CHARLS).MethodsThe bidirectional association between pain and sleep disturbance was assessed using multivariate logistic regression models, adjusting for various covariates.ResultsAmong individuals without pain, those with unsatisfactory sleep quality were more likely to experience future pain, with an adjusted odds ratio (OR) of 1.74 (95% CI: 1.57 - 1.92). Conversely, among individuals with satisfactory sleep quality, those with pain were more likely to develop unsatisfactory sleep quality in the future, with an adjusted OR of 1.87 (95% CI: 1.69 - 2.07). Additionally, shorter sleep duration (&lt;6 hours) was significantly associated with pain status (OR=1.39; 95% CI: 1.28 - 1.50). The incidence of developing short sleep duration in individuals with pain was also higher (OR=1.49; 95% CI: 1.38 - 1.61).ConclusionsThis research revealed a bidirectional relationship between pain and sleep disturbance in middle-aged and older Chinese adults, where each condition exacerbated the other. Recognizing and addressing this interconnected relationship was essential for effective management of both pain and sleep quality in this population.