Objective To explore the relationships of vitamin D and oxidized low-density lipoprotein(ox-LDL)with infertility in patients with polycystic ovary syndrome(PCOS)based on restricted cubic spline models.Methods A total of 150 PCOS patients were selected as the study subjects and followed up for at least 1 year.They were divided into infertile group and non-infertile group according to whether they were infertile.A Logistic regression model was used to analyze the influencing factors of infertility in PCOS patients.Furthermore,the relationships of 1,25-dihydroxyvitamin D3[1,25-(OH)2D3]and ox-LDL with infertility in PCOS patients,as well as their interactive effects on infertility in PCOS patients were analyzed.A restricted cubic spline model was used to analyze the non-linear relationships between 1,25-(OH)2D3,ox-LDL,and infertility in PCOS patients.Results Among 150 PCOS patients,78 were not pregnant,resulting in an infertility rate of 52.00％(78/150).Multivariate Logistic regression analysis showed that the severity of PCOS,body mass index,age,1,25-(OH)2D3,and ox-LDL were all independent influencing factors for infertility in PCOS patients(P＜0.05).After adjusting for confounding factors,1,25-(OH)2D3 and ox-LDL were still associated with the risk of in-fertility in PCOS patients(P＜0.05).Restricted cubic spline model analysis revealed non-linear rela-tionships between 1,25-(OH)2D3,ox-LDL,and the risk of infertility in PCOS patients(P＜0.05).When the serum 1,25-(OH)2D3 level was＜35.70 nmol/L,it was negatively correlated with the risk of infertility in PCOS patients(P＜0.05).When the serum ox-LDL level was ≥381.00 μg/L,it was positively correlated with the risk of infertility in PCOS patients(P＜0.05).Interactive effect analysis showed that 1,25-(OH)2D3 and ox-LDL had antagonistic effects on infertility in PCOS pa-tients(P＜0.05).Conclusion Decreased serum 1,25-(OH)2D3 levels and increased ox-LDL levels in PCOS patients can significantly increase the risk of infertility.Moreover,there is a non-lin-ear dose-response relationship and an antagonistic interactive effect between them,suggesting that regulating vitamin D and oxidative stress levels may be an important strategy for improving the fertili-ty outcomes of PCOS patients.

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

To investigate the role of intestinal fungi in the progression of heart failure (HF) associated with chronic kidney disease (CKD).

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Objective:To explore a simple method for measuring the dynamic intrinsic positive end-expiratory pressure (PEEPi) during invasive mechanical ventilation.Methods:A 60-year-old male patient was admitted to the critical care medicine department of Dongying People's Hospital in September 2020. He underwent invasive mechanical ventilation treatment for respiratory failure due to head and chest trauma, and incomplete expiratory flow occurred during the treatment. The expiratory flow-time curve of this patient was served as the research object. The expiratory flow-time curve of the patient was observed, the start time of exhalation was taken as T 0, the time before the initiation of inspiratory action (inspiratory force) was taken as T 1, and the time when expiratory flow was reduced to zero by inspiratory drive (inspiratory force continued) was taken as T 2. Taking T 1 as the starting point, the follow-up tracing line was drawn according to the evolution trending of the natural expiratory curve before the T 1 point, until the expiratory flow reached to 0, which was called T 3 point. According to the time phase, the intrapulmonary pressure at the time just from expiratory to inspiratory (T 1 point) was called PEEPi 1. When the expiratory flow was reduced to 0 (T 2 point), the intrapulmonary pressure with the inhaling power being removed hypothetically was called PEEPi 2. And it was equal to positive end-expiratory pressure (PEEP) set in the ventilator at T 3 point. The area under the expiratory flow-time curve (expiratory volume) between T 0 and T 1 was called S 1. And it was S 2 between T 0 and T 2, S 3 between T 0 and T 3. After sedation, in the volume controlled ventilation mode, approximately one-third of the tidal volume was selected, and the static compliance of patient's respiratory system called "C" was measured using the inspiratory pause method. PEEPi 1 and PEEP 2 were calculated according to the formula "C =ΔV/ΔP". Here, ΔV was the change in alveolar volume during a certain period of time, and ΔP represented the change in intrapulmonary pressure during the same time period. This estimation method had obtained a National Invention Patent of China (ZL 2020 1 0391736.1). Results:① PEEPi 1: according to the formula "C =ΔV/ΔP", the expiratory volume span from T 1 to T 3 was "S 3-S 1", and the intrapulmonary pressure decreased span was "PEEPi 1-PEEP". So, C = (S 3-S 1)/(PEEPi 1-PEEP), PEEPi 1 = PEEP+(S 3-S 1)/C. ②PEEPi 2: the expiratory volume span from T 2 to T 3 was "S 3-S 2", and the intrapulmonary pressure decreased span was "PEEPi 2-PEEP". So, C = (S 3-S 2)/(PEEPi 2-PEEP), PEEPi 2 = PEEP+(S 3-S 2)/C. Conclusion:For patients with incomplete expiratory during invasive mechanical ventilation, the expiratory flow-time curve extension method can theoretically be used to estimate the dynamic PEEPi in real time.

Objective To evaluate safety and efficacy of linaclotide combined with polyethylene glycol(PEG)for bowel preparation.Methods A total of 612 patients from Department of Gastroenterology at the Affiliated Hospital of Qingdao University for colonoscopy examination from January to June 2023 were selected.They were divided into group 1(1 L PEG+2 L PEG),group 2(linaclotide+2 L PEG)and group 3(1 L PEG+linaclotide+1 L PEG)by random number table method,with 204 cases in each group.The Ottawa Bowel Preparation Quality Scale(OBPS),the insertion time of colonoscopy,the time of the first defecation,the frequency of defecations,the occurrence of adverse effects and patients'tolerability were compared among the three groups.Results A total of 601 patients completed bowel preparation and accepted colonoscopy.Group 1 exhibited no statistically significant differences to group 2 with regards to OBPS and insertion time.However,Group 2 demonstrated a shorter duration for the time of the first defecation in comparison to both group 1 and group 3(P＜0.05).Group 1 displayed a higher frequency of defecations as compared to Group 2 and Group 3(P＜0.05).The incidence of adverse reactions was significantly lower in group 2 and group 3 than in group 1(P＜0.05).The overall tolerance score of patients in group 1 was low-er than that in group 2 and group 3(P＜0.05).Conclusions The effect of combining 2 L PEG with 290 μg of lina-clotide for bowel preparation before colonoscopy is similar to that of 3 L PEG.It can reduce the incidence of adverse reactions and patients exhibit good tolerance.For patients who are intolerant to a single high-dose administration of PEG,they need divided-dose regimen of 2 L PEG in combination with linaclotide.

Objective:To investigate the relationship between different obesity metabolic phenotypes and the incidence of new carotid artery plaque.Methods:The present study is a retrospective cohort study, collecting individuals from the Health Management Center of the Second Affiliated Hospital of Dalian Medical University who had two or more cervical vascular color ultrasound examinations and met the inclusion criteria from 2014 to 2022, and collected their baseline clinical data. According to whether the subjects were obese and had metabolic syndrome, they were divided into metabolically healthy non-obese group, metabolically unhealthy non-obese group, metabolically healthy obese group, and metabolically unhealthy obese group. The first physical examination time of the subjects was taken as the starting point of follow-up, and cervical vascular color ultrasound was performed during the follow-up physical examination, with the outcome event being carotid artery plaque. Kaplan-Meier survival curve analysis was used to analyze the cumulative incidence of carotid artery plaques in the four groups and log-rank test was performed, and a multifactorial Cox proportional hazards model was used to analyze the relationship between different obesity metabolic phenotypes and the risk of carotid artery plaque incidence.Results:A total of 4 890 subjects were enrolled, aged (45.4±9.6) years, and 2 754 (56.3%) males. The follow-up time was 1.14(0.93, 2.20) years. Compared with the other 3 obesity metabolic phenotypes, the incidence of carotid plaques in the metabolically unhealthy obesity group was the highest (15.4% (286/1 861)). Kaplan-Meier survival curve analysis showed that the cumulative incidence of carotid plaques in metabolically unhealthy obese subjects was about 2.962 times that of metabolically healthy non-obese subjects (log-rank P<0.001). Multivariate Cox regression results showed that the risk of carotid plaque in metabolically unhealthy obese subjects was 1.650 times that of metabolically healthy non-obese subjects (95% CI: 1.203-2.264, P=0.002). Conclusion:Metabolically unhealthy obesity phenotype is an independent risk factor for carotid plaque.

Objective:To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU).Methods:The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children′s Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods.Results:Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering.Conclusions:For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.

Objective:To investigate the relationship between obesity and incident chronic kidney disease(CKD) in a population undergoing health check-ups.Methods:This is a retrospective cohort study. A total of 31 251 participants who had at least 2 health physical examinations in the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 2017 to December 2022 and met the inclusion criteria were selected. The participants were divided into normal body weight group, overweight group, and obese group according to baseline body mass index. Cox proportional hazard regression model was used to analyze the relationship between obesity and new-onset CKD, and the dose-response relationship between body mass index and CKD was analyzed with restricted cubic splines.Results:Multivariate Cox regression analysis showed that the risk of developing CKD increased by 13%( HR=1.13, 95% CI 1.01-1.25) and 55%( HR=1.55, 95% CI 1.36-1.76) in the overweight and obese group compared to the normal weight group. Subgroup analysis indicated that obese women had a higher risk of developing CKD compared to men. There was a " U-shaped" correlation between body mass index and CKD in male population, with the lowest risk of CKD occurring at body mass index of 19.6-24.2 kg/m 2. In women, the relationship between body mass index and CKD was approximately linear, with the risk of CKD gradually increasing when body mass index exceeded 22.5 kg/m 2. Conclusions:Obesity is an independent risk factor for new-onset CKD, and obese women have a higher risk of developing CKD than men. Regarding CKD prevention, men are advised to maintain a higher level of body weight within the normal range of body mass index, while women are encouraged to control their weight to a lower level within the normal body mass index range.