bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of growth hormone on the outcomes of in vitro fertilization and embryo transfer in age-grouped patients with decreased ovarian reserve: a prospective cohort study
Authors: Chen Jiexiu , Kong Xumei , Luan Zonghui , Qiu Yu , Chen Shiqi , Li−Ling Jesse , Gong Yan 
Published: January 2025

BackgroundGrowth hormone (GH) could improve the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in patients with decreased ovarian reserve (DOR), but which age group will benefit the most has remained controversial. This study aims to explore the outcome of IVF-ET among differently aged patients with DOR treated with GH.MethodsA total of 846 patients with DOR undergoing IVF-ET from May 2018 to June 2023 at the Reproductive Medicine Center of Sichuan Provincial Women’s and Children’s Hospital were prospectively enrolled. The patients were divided into group A (&lt; 35 year old, n = 399), group B (35 ~ 40 year old, n = 286), and group C (&gt; 40 year old, n = 161). Each group was sub-divided into the GH part and the control part, with the former receiving pretreatment with GH 4 IU/day on day 2 of the previous menstrual cycle before the injection of gonadotrophin (Gn) until the trigger day. The ovarian stimulation protocol was gonadotrophin-releasing hormone antagonist (GnRH-A) or long-acting GnRH agonist protocol. The quality of oocytes and embryos and the outcome of pregnancy were compared.ResultsIn group B, the number (1.16 ± 0.12 vs. 0.74 ± 0.09) and rate (34.27% vs. 23.90%) of high-quality cleavage embryos, rate of implantation (32.37% vs. 22.35%), clinical pregnancy (48.98% vs. 33.67%), and live birth (44.90% vs. 29.59%) were significantly higher, whereas the canceled oocyte retrieval rate was significantly lower (1.49% vs. 6.58%) in the GH part than those of the control part (P &lt; 0.05). In group B, the duration and dose of Gn, number of oocyte retrieved, and rates of normal fertilization, cleavage embryo, blastocyst, high-quality blastocyst, and early miscarriage were not significantly different between the GH and control parts (P &gt; 0.05). In groups A and C, no significant difference was detected in the quality of embryos and outcomes of embryo transfer with or without pretreatment (P &gt; 0.05).ConclusionGH could improve the quality of embryos and live birth rate for patients with DOR aged 35–40 years old.
Nomogram-derived immune-inflammation-nutrition score could act as a novel prognostic indicator for patients with head and neck squamous cell carcinoma
Authors: Wang Wen-Yan , Chen Yue , Chen Qian , Sun Hong-Wei , Niu Nuo-Xuan , Li Hong-Hui , Cao Yu-Dan , Bai Yan-Xia , Li Xiang 
Published: January 2025

AimThis study aims to create and validate a novel systematic immune-inflammation-nutrition (SIIN) score to provide a non-invasive and accurate prognostic tool for head and neck squamous cell carcinoma (HNSCC) patients.Methods259 participants diagnosed with HNSCC from the First Affiliated Hospital of Xi’an Jiaotong University between 2008 and 2017 was included in this retrospective study. Patients were assigned to training (n=181) and validation (n=78) sets. A LASSO Cox regression model was employed to identify significant biomarkers for constructing a SIIN nomogram and to create SIIN score from this nomogram. The prognostic accuracy of the SIIN score was assessed by exploiting receiver operating characteristic (ROC) analysis, Kaplan-Meier survival analysis, Cox proportional hazard regression models, calibration and DCA curves.ResultsThe SIIN score was formulated based on six biomarkers-platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), albumin-bilirubin index (ALBI), fibrinogen (FIB) and monocyte count-identified by LASSO regression analysis. (1)The SIIN score demonstrated superior predictive value, achieving area under the ROC curve (AUC) values of 0.736 and 0.700 for 3- and 5-year OS. For recurrence-free survival (RFS), the AUC values were 0.752 for 3-year and 0.701 5-year RFS, as assessed in the training set. Validated as an independent prognostic factor in both cohorts, the SIIN score showed strong correlation with adverse clinicopathological outcomes.ConclusionThe SIIN score is a promising prognostic tool that integrates immune, inflammatory, and nutritional factors for predicting clinical outcomes in HNSCC patients. It offers enhanced predictive accuracy compared to existing markers and has the potential to guide personalized treatment strategies and clinical decision-making.
The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity
Authors: Kindstedt Elin , de Vries Charlotte , Wänman Magnus , Potempa Barbara Aleksandra , Potempa Jan , Lindquist Susanne , Esberg Anders , Lundberg Karin , Lundberg Pernilla 
Published: January 2025

IntroductionPeriodontitis is associated with rheumatoid arthritis (RA). One hypothesis posits that this connection arises from the formation of autoantibodies against citrullinated proteins (ACPA) in inflamed gums, possibly triggered by Porphyromonas gingivalis. We previously demonstrated an increased antibody response to P. gingivalis arginine gingipains (anti-Rgp IgG), not only in individuals with severe periodontitis compared to controls, but in RA versus controls, with an association to ACPA. In the present study, we set out to further explore the relationship between anti-Rgp IgG, ACPA and periodontitis, including clinical periodontal parameters, in the large and well-characterized PerioGene North case-control study.MethodsWe measured serum levels of anti-Rgp and ACPA IgG by enzyme-linked immunosorbent assay (ELISA), in 478 patients with periodontitis and 509 periodontally healthy controls within PerioGene North. Subsequently, anti-Rgp IgG levels and ACPA status were analysed in relation to periodontitis and clinical periodontal parameters.ResultsSerum anti-Rgp IgG levels were elevated in cases versus controls (p&lt; 0.001). However, receiver operating characteristic (ROC) curve analysis revealed that anti-Rgp IgG could not efficiently discriminate cases from controls (AUC= 0.63; 95% CI: 0.60 – 0.66). Among cases, increased anti-Rgp IgG levels associated with high periodontal inflammation and advanced alveolar bone loss (p&lt;0.001 for both). An ACPA response was detected in 15 (3.1%) cases and 6 (1.2%) controls (p=0.033), but no association to periodontitis was evident after adjustment for age and smoking and anti-Rgp IgG levels did not differ between ACPA-positive and ACPA-negative individuals.ConclusionWe show that anti-Rgp IgG identifies a subgroup of periodontitis patients with high degree of periodontal inflammation and advanced alveolar bone loss, but we do not find support for a link between periodontitis or anti-Rgp IgG and ACPA status in PerioGene North. Given the association between anti-Rgp and alveolar bone loss, the mechanistic role of gingipains in bone resorption should be experimentally explored.
Network pharmacology and multi-omics validation of the Jianpi-Yishen formula in the treatment of chronic kidney disease
Authors: Li Yuyan , Luo Yueming , Hu Yilan , Li Siting , Li Guandong , Zhang Wanyangchuan , Gu Xiufen , Wang Jianting , Li Shunmin , Cheng Hong 
Published: January 2025

ObjectiveChronic kidney disease (CKD) is a major global health problem. In clinical practice, the Chinese patent herbal medicine Jianpi-Yishen (JPYS) formula is commonly used to treat CKD. However, the molecular mechanisms by which JPYS targets and modulates the host immune response remain unclear.MethodsThis study utilized network pharmacology, RNA sequencing (RNA-seq), and metabolic analyses using in vivo and in vitro models to investigate the impact of the JPYS formula on inflammation and the immune system. Specifically, the study focused on macrophage polarization and metabolic changes that may slow down the progression of CKD.ResultsA total of 14,946 CKD-related targets were identified from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases through network pharmacology analyses. 227 potential targets of the JPYS formula were predicted using the TCMSP database. Additionally, network diagram demonstrated that 11 targets were associated with macrophage activity. In vivo studies indicated that the JPYS formula could reduce blood urea nitrogen and serum creatinine in adenine-induced CKD rats. Furthermore, the formula inhibited inflammatory damage and abnormal macrophage infiltration in this CKD model. RNA-seq, proteomic and metabolic analyses identified the regulation of amino acid metabolism by betaine, specifically referring to glycine, serine, and threonine metabolism, as a key target of the JPYS formula in slowing the progression of CKD. In addition, in vitro studies suggested that JPYS may enhance tryptophan metabolism in M1 macrophage polarization and betaine metabolism in M2 macrophage polarization.ConclusionsThe JPYS formula has been shown to have beneficial impact on CKD; a key mechanism is the mitigation of inflammatory damage through the interaction between amino acid metabolism and macrophage polarization. Of specific importance in this context are the roles of tryptophan in M1 polarization and betaine in M2 polarization.
Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis
Authors: Chen J. Q. Alida , Wever Dennis D. , McNamara Niamh B. , Bourik Morjana , Smolders Joost , Hamann Jörg , Huitinga Inge 
Published: January 2025

IntroductionRemyelination of demyelinated axons can occur as an endogenous repair mechanism in multiple sclerosis (MS), but its efficacy varies between both MS individuals and lesions. The molecular and cellular mechanisms that drive remyelination remain poorly understood. Here, we studied the relation between microglia activation and remyelination activity in MS.MethodsWe correlated regenerative (CD163+) and inflammatory (iNOS+) microglia with BCAS1+ oligodendrocytes, subdivided into early-stage (&lt;3 processes) and late-stage (≥3 processes) cells in brain donors with high or low remyelinating potential in remyelinated lesions and active lesions with ramified/amoeboid (non-foamy) or foamy microglia. A cohort of MS donors categorized as efficiently remyelinating donors (ERDs; n=25) or poorly remyelinating donors (PRDs; n=17) was included, based on their proportion of remyelinated lesions at autopsy.Results and discussionWe hypothesized more CD163+ microglia and BCAS1+ oligodendrocytes in remyelinated and active non-foamy lesions from ERDs and more iNOS+ microglia with fewer BCAS1+ oligodendrocytes in active foamy lesions from PRDs. For CD163+ microglia, however, no differences were observed between MS lesions and MS donor groups. In line with our hypothesis, we found that INOS+ microglia were significantly increased in PRDs compared to ERDs within remyelinated lesions. MS lesions, more late-stage BCAS1+ oligodendrocytes were detected in active lesions with non-foamy or foamy microglia in comparison with remyelinated lesions. Although no differences were found for early-stage BCAS1+ oligodendrocytes between MS lesions, we did find significantly more early-stage BCAS1+ oligodendrocytes in PRDs vs ERDs in remyelinated lesions. Interestingly, a positive correlation was identified between iNOS+ microglia and the presence of early-stage BCAS1+ oligodendrocytes. These findings suggest that impaired maturation of early-stage BCAS1+ oligodendrocytes, encountering inflammatory microglia, may underlie remyelination deficits and unsuccessful lesion repair in MS.
Efficacy and safety of anlotinib as maintenance treatment in extensive-stage small cell lung cancer: a single-armed single center retrospective study
Authors: Xiong Jin , Xia Lei 
Published: January 2025

IntroductionPatients with extensive-stage small cell lung cancer (ES-SCLC) have a poor Q6 prognosis and there is no standard protocol for maintenance treatment. Anlotinib as a third-line or beyond therapy for ES-SCLC was proved to be effective.MethodsWe retrospectively screened of patients with ES-SCLC who started receiving anlotinib as first-line or second-line therapy at the Second Affiliated Hospital of Chongqing Medical University from November 2018 to December 2022. 30 patients treated with anlotinib based combination therapy and subsequent maintenance therapy were included. The primary study endpoint was progression-free survival (PFS) and the secondary study endpoints were overall survival (OS), clinical response and adverse events (AEs).Results and discussionIn 30 ES-SCLC patients, the median PFS and OS were 7.2 months and 17.6 months respectively. The ORR and DCR were 50.0% (15/30) and 86.7% (26/30) respectively. The median PFS was 8.2 months and 5.6 months for patients who received synchronized immunotherapy or chemotherapy. The median OS was 20.1 months and 15.1 months for patients who received synchronized immunotherapy or chemotherapy. The median time to intracranial progression (TTP) was 7.2 months for patients who were without brain metastases before receiving anlotinib. No unexpected AEs were reported. Grade 3-4 adverse events were reported in 10 patients (33.3%). No treatment-related deaths occurred during this study. Our study has indicated the good efficacy and safety about the application of anlotinib in the maintenance therapy in the first-line or second-line treatment of ES-SCLC and it can also achieve good intracranial control.
Global, regional and national burden of pancreatic cancer and its attributable risk factors from 2019 to 2021, with projection to 2044
Authors: Li Xiao , Zhang Yi , Yan Zeyi , Jiang Wenkai , Rui Shaozhen 
Published: January 2025

BackgroundTo estimate the global burden of pancreatic cancer in 2019 and 2021 including incidence, mortality, and disability-adjusted-life-years (DALYs).MethodsData on pancreatic cancer incidence, mortality and DALYs were downloaded from the Global Health Data Exchange. The 95% uncertainty intervals (UIs) were reported for annual numbers and rates (per 100,000 populations).ResultsIn 2021, there were 508,532 (95% UI: 462,09 to 547,208) incident cases of pancreatic cancer globally, of which 273,617 (250,808 to 299,347; 53.8%) were in males. The age-standardized incidence rate was 6.0 (5.5 to 6.5) per 100,000 people in 2019 and decreased to 5.9 (5.4 to 6.4) per 100,000 people in 2021. There was a 3.9% increase in the number of deaths from pancreatic cancer from 486,869 (446,272 to 517,185) in 2019 to 505,752 (461,224 to 543,899) in 2021. There was a 3.5% increase in DALYs due to pancreatic cancer, increasing from 10.9 million (10.1 to 11.7) in 2019 to 11.3 million (10.5 to 12.2) in 2021. In 2021, the highest age-standardized death rates were observed in Greenland and Monaco, and the highest age-standardized DALY rates were observed in Greenland and Uruguay. The numbers of incident cases and deaths peaked at the ages of 70 to 74 years. The pancreatic cancer burden increased as the socio-demographic index increased. To 2044, the number of incident cases and deaths will be more than 875 thousand and 879 thousand, respectively.ConclusionThe disease burden of pancreatic cancer remains high, especially in high-income regions. More cancer prevention measures are needed in the future to reduce the burden of pancreatic cancer.
Platelet count and retinopathy of prematurity, a systematic review and meta-analysis
Authors: Zeng Qian , Wang Ling , Li Yurong , Yue Yuanyuan , Lv Xin 
Published: January 2025

ObjectiveThis study aims to investigate the relationship between platelet count (PLT) and retinopathy of prematurity (ROP), with the goal of identifying a straightforward screening method for the early detection of ROP.MethodsA systematic search was conducted in PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov from January 2005 to 26 September 2023. Subsequently, a subgroup analysis was performed.ResultsThis meta-analysis included ten studies involving 1762 neonates, with 747 cases of ROP identified. The pooled analysis indicated a significant decrease in mean platelet count among the ROP group compared to the non-ROP group (mean difference: −18.65, 95% confidence interval: −22.80 to −14.50, P &lt; .00001). Subgroup analysis indicated that the heterogeneity in the results can be attributed to factors such as the location of the studies, gestational age (GA), and publication time.ConclusionDecreased PLT counts may be associated with the occurrence of ROP. The PLT count should be standardized according to the detection location, detection time and GA.
Panzerina lanata accelerates methicillin-resistant Staphylococcus aureus eradication by promoting migration and activation of neutrophils
Authors: Dong Shuai , Bai Xingyuan , Chen Bin , Fan Minzhe , Liu Qi , Zhao Yubo , Li Linsen , Zhu Dan 
Published: January 2025

BackgroundPanzerina lanata (Lanata) is generally used to treat pustule infection in Inner Mongolia folk medicine and is called “the holy medicine for pustule.” However, the pharmacological mechanism of Lanata in treating pustule infection is still unclear.AimsThis study aimed to investigate the therapeutic effects of Lanata on skin infection and explore the underlying mechanisms.MethodsA skin wound methicillin-resistant Staphylococcus aureus (MRSA) infection mouse model was established to evaluate the healing effect of Lanata on infected wounds. In vitro assays were also conducted to determine the antibacterial activity of Lanata. Flow cytometry and immunohistochemistry were used to dynamically detect the number of neutrophils in the bone marrow, peripheral blood, and MRSA-infected wound. Protein expression in the infected wound skin was detected by a protein chip. Using an air pouch MRSA infection mouse model, the number of neutrophils, reactive oxygen species (ROS) level in neutrophils, and neutrophil extracellular trap (NET) formation were dynamically detected by flow cytometry and immunofluorescence. RNA-seq, RT-qPCR, flow cytometry, ELISA, and CXC chemokine receptor 2 (CXCR2) and P-selectin glycoprotein ligand-1 (PSGL-1) inhibitors were used to explore the mechanism of Lanata in regulating neutrophils.ResultsIn vitro assays showed that Lanata had no direct antibacterial activity. In skin wound MRSA-infected mouse, Lanata promoted the rapid migration of neutrophils from the bone marrow via peripheral blood to the wound site to eradicate MRSA in the acute stage of infection and accelerate wound healing. Skin protein chip analysis showed that Lanata upregulated CXCR2 and PSGL-1 protein levels in skin wounds. Furthermore, analysis using the air pouch MRSA infection mouse model found that Lanata not only promoted the rapid migration of neutrophils from peripheral blood to the air pouch but also enhanced the activation of neutrophils, including the increase of ROS and the release of NETs, and upregulated the expression of CXCR2, PSGL-1, and myeloperoxidase (MPO) in neutrophils. Inhibition of CXCR2 and MPO significantly attenuated the effect of Lanata on promoting migration and activation of neutrophils.ConclusionPanzerina lanata resists MRSA infection by promoting migration and activation of neutrophils to rapidly eradicate MRSA.
Therapeutic potential of rutin in premenstrual depression: evidence from in vivo and in vitro studies
Authors: Wang Xiangjun , Xia Xiaowen , Song Xianliang , Zhou Yi , Ma Mingyu , Ren Yashuang , Chen Xitai , Xia Zenghui , Guo Yinghui , Song Chunhong 
Published: January 2025

IntroductionPremenstrual dysphoric disorder (PMDD) is a cyclical mood disorder that severely affects the daily life of women of reproductive age. Most of the medications being used clinically have limitations such as low efficacy, side effects, and high cost, so there is an urgent need to discover safer and more effective medications. Rutin is a natural flavonol glycoside with various pharmacological properties including antidepressant. The study of the efficacy and mechanism of action of rutin in PMDD-depressed subtype model rats plays an important role in the discovery of new drugs for the treatment of PMDD.MethodsBinding of rutin to gamma-aminobutyric acid type A receptors (GABAA receptors) was probed using molecular docking, microscale thermophoresis, radioactive receptor ligand binding assay and cell membrane clamp experiment. Behavioral tests in mice were performed to screen the optimal dose of rutin. Behavioral tests were performed to evaluate the effects of rutin on depressed mood, memory impairment, and social impairment in PMDD-depressed subtype model rats. HE staining and Golgi staining were performed to observe the neuronal damage in rat hippocampus. UHPLC-MS/MS targeted metabolomics was performed to detect the changes of neurotransmitter content in rat hippocampus. PCR array to detect the effect of rutin on mRNA expression of GABAA receptor partial subunits in rat hippocampus.ResultsThe docking score of rutin with the GABAA receptor benzodiazepine site was −11.442 and the gliding score was −11.470. The Kd of rutin with the GABAA receptor (α1β2γ2) was 1.17 ± 0.89 μM. Rutin competed with [H3]-flunitrazepam for the GABAA receptor benzodiazepine site and inhibited the inward flow of chloride ions (P &lt; 0.05). In PMDD-depressed subtype rats, rutin alleviated depressed mood, memory impairment and social impairment, ameliorated hippocampal neuronal damage and reduces gamma-aminobutyric acid (GABA) and acetylcholine (ACh) levels (P &lt; 0.05). Moreover, we found that rutin did not affect the relative mRNA expression of GABAA receptor subunits in rat hippocampus.DiscussionOverall, rutin alleviated depressed mood, memory impairment and social impairment in PMDD-depressed subtype rats, which may be related to binding to GABAA receptor benzodiazepine sites, inhibiting chloride ions inward flow, ameliorating hippocampal neuronal damage and reducing GABA and ACh levels. The results of this study provide an experimental basis and scientific evidence for the development of new drugs for the treatment of PMDD.