Arbuscular Mycorrhizal Fungi Improve Lycium barbarum Potassium Uptake by Activating the Expression of LbHAK.

Arbuscular mycorrhizal (AM) fungi can establish a mutualistic relationship with the roots of most terrestrial plants to increase plant nutrient uptake. The effects of potassium uptake and transport by AM symbiosis are much less reported compared to other nutrients. In this research, a heterologous yeast system was used to verify that the LbHAK has capacity for potassium uptake. The split-roots system implemented using seedlings of Lycium barbarum confirmed that R. irregularis locally induced LbHAK expression, which means that LbHAK is only expressed in mycorrhizal roots. Furthermore, the impacts of overexpression of LbHAK on the growth, nutrients and water uptake, and transport of mycorrhizal tobacco (inoculation with Rhizophagus irregularis) at 0.2 mM and 2 mM K conditions were assessed. The mycorrhizal tobacco growth and potassium accumulation were significantly enhanced through LbHAK overexpression in tobacco. In addition, overexpression of LbHAK substantially enhanced phosphorus content, while stimulating the expression of NtPT4, Rir-AQP1, and Rir-AQP2 in mycorrhizal tobacco. Moreover, LbHAK overexpression greatly promoted AM colonization. LbHAK has a potential role in facilitating potassium absorption through the mycorrhizal pathway, and overexpression of LbHAK in tobacco may promote the transport of potassium, phosphorus, and water from AM fungi to tobacco. These data imply the important roles played by the LbHAK in AM-fungi-induced potassium uptake in L. barbarum and in improving plant nutrients and AM colonization.

Association between CYP2C9 and VKORC1 genetic polymorphisms and efficacy and safety of warfarin in Chinese patients.

OBJECTIVES: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. METHODS AND RESULTS: Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage ( P  < 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratio = 2.16, P  = 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications ( P  < 0.00001), VKORC1 did not demonstrate a similar association. CONCLUSION: The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.

Enhanced Biphasic Reactions in Amphiphilic Silica Mesopores.

In this study, we investigated the effect of the pore volume and mesopore size of surface-active catalytic organosilicas on the genesis of particle-stabilized (Pickering) emulsions for the dodecanal/ethylene glycol system and their reactivity for the acid-catalyzed biphasic acetalization reaction. To this aim, we functionalized a series of fumed silica superparticles (size 100-300 nm) displaying an average mesopore size in the range of 11-14 nm and variable mesopore volume, with a similar surface density of octyl and propylsulfonic acid groups. The modified silica superparticles were characterized in detail using different techniques, including acid-base titration, thermogravimetric analysis, TEM, and dynamic light scattering. The pore volume of the particles impacts their self-assembly and coverage at the dodecanal/ethylene glycol (DA/EG) interface. This affects the stability and the average droplet size of emulsions and conditions of the available interfacial surface area for reaction. The maximum DA-EG productivity is observed for A200 super-SiNPs with a pore volume of 0.39 cm3·g-1 with an interfacial coverage by particles lower than 1 (i.e., submonolayer). Using dissipative particle dynamics and all-atom grand canonical Monte Carlo simulations, we unveil a stabilizing role of the pore volume of porous silica superparticles for generating emulsions and local micromixing of immiscible dodecanal and ethylene glycol, allowing fast and efficient solvent-free acetalization in the presence of Pickering emulsions. The micromixing level is interrelated to the adsorption energy of self-assembled particles at the DA/EG interface.

Epigenetic regulations of cellular senescence in osteoporosis.

Osteoporosis (OP) is a prevalent age-related disease that is characterized by a decrease in bone mineral density (BMD) and systemic bone microarchitectural disorders. With age, senescent cells accumulate and exhibit the senescence-associated secretory phenotype (SASP) in bone tissue, leading to the imbalance of bone homeostasis, osteopenia, changes in trabecular bone structure, and increased bone fragility. Cellular senescence in the bone microenvironment involves osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells (BMSCs), whose effects on bone homeostasis are regulated by epigenetics. Therefore, the epigenetic regulatory mechanisms of cellular senescence have received considerable attention as potential targets for preventing and treating osteoporosis. In this paper, we systematically review the mechanisms of aging-associated epigenetic regulation in osteoporosis, emphasizing the impact of epigenetics on cellular senescence, and summarize three current methods of targeting cellular senescence, which is helpful better to understand the pathogenic mechanisms of cellular senescence in osteoporosis and provides strategies for the development of epigenetic drugs for the treatment of osteoporosis.

Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update.

ABSTRACT: Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the third- or later-line setting. The primary analysis (median follow-up, 17 months) of the phase 2 ELARA trial reported high response rates and excellent safety profile in patients with extensively pretreated r/r FL. Here, we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after median follow-up of 29 months (interquartile range, 22.2-37.7). As of 29 March 2022, 97 patients with r/r FL (grades 1-3A) received tisagenlecleucel infusion (0.6 × 108-6 × 108 chimeric antigen receptor-positive viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment, blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached. Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% confidence interval [CI], 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2), respectively. Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T cells and higher baseline levels of naïve CD8+ T cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA. This trial was registered at www.clinicaltrials.gov as #NCT03568461.

Risk Factors Analysis and Pathogen Distribution of Urinary Tract Infection in Patients Undergoing Cutaneous Ureterostomy After Radical Cystectomy for Bladder Cancer.

BACKGROUND: Postoperative urinary tract infection is a common complication that not only significantly prolongs the hospital stay and amplifies the economic burden on patients, but also affects their quality of life and prognosis. This study aimed to investigate risk factors and distribution of pathogenic bacteria in urinary tract infections among bladder cancer patients who underwent cutaneous ureterostomy following radical cystectomy. METHODS: A total of 137 bladder cancer patients, who underwent cutaneous ureterostomy after radical cystectomy at our hospital from November 2018 to October 2022, were enrolled in this retrospective study. Univariate and multivariate logistic regression analyses were employed to investigate the risk factors associated with postoperative urinary tract infection and the distribution of pathogenic bacteria among the infected patients. RESULTS: The results of both univariate and multivariate analyses confirmed that age, proficiency in ostomy knowledge, frequency of ureteral stent tube replacement, ureteral stent tube dislodgement, urine immersion at the outer end of the ureteral stent tube, and the interval of ostomy bag replacement were independent risk factors for urinary tract infection after radical cystectomy and cutaneous ureterostomy in bladder cancer patients. A total of 55 pathogenic bacteria were isolated from 52 patients with infections. Predominantly, these were gram-negative bacteria (34 strains, 61.8%), with Proteus mirabilis having the highest proportion. CONCLUSION: Urinary tract infections after radical cystectomy and cutaneous ureterostomy predominantly involve gram-negative bacteria. This is correlated with factors such as the age of bladder cancer patients, the level of nursing education, the duration of ureteral stent tubes and ostomy bag usage, as well as issues related to impaired urine drainage.

Feasibility of using chest computed tomography (CT) imaging at the first lumbar vertebra (L1) level to assess skeletal muscle mass: a retrospective study.

Background: Skeletal muscle mass is an essential parameter for diagnosing sarcopenia. The gold standard for assessing skeletal muscle mass is using computed tomography (CT) to measure skeletal muscle area at the third lumbar vertebra (L3) level. This study aims to investigate whether skeletal muscle mass could be evaluated at the first lumbar vertebra (L1) level using images obtained from routine chest CT scans. Methods: Skeletal muscle index (SMI, cm2/m2) and skeletal muscle density (SMD, HU) are commonly used to measure relative muscle mass and the degree of fat infiltration. This study used CT images at the L1 level to measure the skeletal muscle area (SMA, cm2) in 815 subjects from the health examination center. Linear regression analysis was used to explore the association between L1 and L3 measurements. The receiver operating characteristic (ROC) analysis was used to assess the predictive performance of L1 SMI for sarcopenia. The sex-specific cut-off values for low skeletal muscle mass in patients under the age of 60 were determined using the following formula: "mean - 1.28 × standard deviation." A multivariate linear regression model was established. Results: A significantly higher SMI at the L1 level was found in males than in females (43.88 ± 6.33 cm2/m2 vs 33.68 ± 5.03 cm2/m2; P < 0.001). There were strong correlations between measures at the L1 and L3 levels in both the total subject and sex-specific analyses. A negative association was found between age and L3 SMI in males (r = -0.231, P = 0.038). Both body mass index (BMI) and body surface area (BSA) were positively associated with L1 SMI in both males and females. A multivariate analysis was used to establish a prediction rule to predict SMI at the L3 level. The assessment of consistency and interchangeability between predicted and actual SMI at the L3 level yielded moderately good results. Considering the significant differences observed between male and female participants, the sex-specific cut-off values of the L1 SMI for defining low skeletal muscle mass were 36.52 cm2/m2 in males and 27.29 cm2/m2 in females. Conclusions: Based on a population from central China, the correlated indicators obtained at the L1 level from routine chest CT scans may serve as effective surrogate markers for those at the L3 level in assessing overall skeletal muscle mass.

Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image.

Lung cancer is the cancer with the highest mortality rate and the highest incidence in the world at this stage. Among them, non-small lung cancer is the most common type of lung cancer, and most small cancers have disappeared, which is the optimal time for surgery at the time of diagnosis. To explore and systematically evaluate the clinical efficacy of CYP1B1 gene polymorphism in the treatment of epidermal growth factor receptor (EGFR) Mutant non-small cell lung cancer, this article proposes the principles of lung cancer screening based on CYP1B1 gene polymorphism and polarization imaging and explores the diagnosis and treatment of non-EGFR mutant lung cancer. Based on a large number of medical image data, imageomics can directly reflect the correlation between tumor molecular phenotype and image characteristics by deeply mining some imaging features of the image, which has important value in the early diagnosis of disease, the formulation of personalized treatment plan, and efficacy evaluation and prognosis prediction. A total of 141 NSCLC patients with sensitive EGFR mutation were included in this study, including 101 patients with EGFR single-gene mutation and 40 patients with EGFR multigene mutation coexisting mutation. Both groups of patients were female, aged ≥60 years, no smoking history, no family history of leukemia, adenocarcinoma, lung cancer, stage IV, lymph node metastasis, living, far from metastasis, and ECOG score of 0-2. This study examined the relative number of gene expression and PFS in EGFR multigene co-existing mutations. When the number of mixed genes is 1, 2, and higher, the PFS is 9 months, 8 months, and 6 months, respectively. The PFS time of this group of patients gradually shortened. Therefore, this study examined the benefit of polygenic mutation in estimation by comparing the clinical characteristics of patients with EGFR single-gene mutation and polygenic mutation, to provide measurement of EGFR-TKI and to provide suggestions for future drug selection.

Islet Like Cells Induced from Umbilical Cord Mesenchymal Stem Cells with Neonatal Bovine Pancreatic Mesenchymal Exosomes for Treatment of Diabetes Mellitus.

To investigate the safety and efficacy of the islet-like cell (cell) induced from human umbilical cord mesenchymal stem cell (UCMSC) with different methods for the treatment of diabetic animal model. UCMSCs were induced to ßcells with cytokines (CY) and neonatal bovine pancreatic mesenchymal cell exosomes (Ex) combined with CY (EX+CY). The insulin secretion of UCMSC and ßcell was measured with ELISA when the cells were growing in different concentrations of glucose media for different times. UCMSCs (4×105) and the same number of cells prepared with two methods were transplanted to type I diabetic rat models. UCMSCs could be induced into islet ßcells by CY or EX+CY in vitro. The insulin secretion of the prepared ß cells growing in 25.0 mM glucose medium was over 5-fold of that in 6.0 mM glucose. The transplantation of the ßcells to type I diabetic rat models could reduce the blood glucose and prolong the survival time. The ß cells induced by EX+CY had much more significant effects on decreasing blood glucose and increasing survival time (p<0.01). The cells did not affect blood sugar level and had no serious side-effects in human health. UCMSC could be induced to islet ßcells with either CY or EX+CY. The transplantation of the induced islet ßcells could reduce blood glucose and prolong the survival time of diabetic animal models. Although the cells induced with EX+CY had more significant effects on diabetic rats, they did not affect blood glucose level and had no serious side-effects in human health.

Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model.

Non-small cell lung cancer (NSCLC) is one of the most common cancers worldwide, and chemotherapy is one of its main treatment methods. However, there are significant differences in patients' reactions to chemotherapy, leading to unsatisfactory treatment outcomes. Therefore, identifying relevant factors that affect the efficacy of chemotherapy can help doctors better develop personalized treatment plans, improve the treatment effectiveness, and quality of life of patients. This article aims to understand the specific clinical role of CYP1B1 gene in NSCLC. Therefore, based on the individualized health model of CYP1B1 gene polymorphism, this article analyzes the prediction of postoperative chemotherapy efficacy for NSCLC. Through a study on the control variables of postoperative recovery of stage III NSCLC in a hospital, according to the findings of this study, 14 of the 32 patients in the EGFR mutation-positive group relapsed. In the EGFR-negative group, 13 of the 36 patients relapsed. It can be considered that CYP1B1 gene polymorphism has a good curative effect in postoperative chemotherapy of NSCLC, and it can effectively control the recurrence rate of cancer.

Self-reported barriers in self-management of women with gestational diabetes: A systematic review of qualitative studies.

AIM: To provide a systematic review of the qualitative literature on self-reported barriers to self-management in pregnant women with gestational diabetes mellitus (GDM). DESIGN: Systematic review. METHODS: This systematic review followed the Joanna Briggs Institute meta-aggregation approach and was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Qualitative studies on the barriers to self-management among GDM pregnancy survivors conducted until 17 May 2022, were searched. RESULTS: A total of 30 studies were included, of which seven were in Chinese and 23 were in English, and 10 findings resulted in three themes: (a) Knowledge and belief, (b) Skills and abilities and (c) Environment and social support. By summarizing the self-reported barriers to self-management in patients with GDM and recommends precise interventions for these barriers, thereby saving health resources and helping to increase their willingness and ability to engage in self-management.

Association of Maternal Cigarette Smoking with Neonatal Death: A Population-Based Cohort Study.

INTRODUCTION: Maternal pregnancy smoking has adverse perinatal outcomes and the relationship between maternal smoking and neonatal death has not been fully elucidated. We aimed to examine the risk of neonatal death in relation to maternal smoking and to quantify potential mediators of these associations. METHODS: We did a population-based cohort study using Period Linked Birth-Infant Death data from 2016 to 2019 in the US National Vital Statistics System. The exposure was maternal smoking status. The main outcome was neonatal death. Association between maternal smoking and neonatal death was estimated through logistic regression. Mediation analysis was performed to assess the extent to which the association between maternal smoking and neonatal death was mediated by neonatal complications. RESULTS: The final sample consisted of 14,717,020 mothers with live singleton births. The overall neonatal mortality rate was 2.2 per 1,000 live births. Maternal pregnancy smoking was associated with an increased risk of neonatal death {adjusted odds ratio (aOR, 1.33 [95% CI, 1.28-1.38]; p < 0.001)}, while smoking cessation during the whole pregnancy showed a comparable risk of neonatal death with nonsmokers (aOR, 1.06 [95% CI, 0.99-1.14]; p = 0.116). Mediation analysis indicated that the association between pregnancy smoking and neonatal death might be mainly mediated by preterm birth and low Apgar score at 5 min. CONCLUSIONS: Maternal pregnancy smoking, regardless of pregnancy trimester and intensity, was associated with increased risk of neonatal death. Efforts are needed for policymakers to promote smoking cessation before pregnancy, and professional perinatal care should be provided for those who smoked during pregnancy.

LbKAT3 may assist in mycorrhizal potassium uptake, and overexpression of LbKAT3 may promote potassium, phosphorus, and water transport from arbuscular mycorrhizal fungi to the host plant.

Potassium plays important roles in most plant physiological processes. Arbuscular mycorrhizal (AM) fungi promote plant water and mineral nutrient acquisition to promote plant growth. However, few studies have focused on the effect of AM colonization on potassium uptake by the host plant. In this study, the effects of an AM fungus (Rhizophagus irregularis) and potassium concentration (0, 3, or 10 mM K+) on Lycium barbarum were evaluated. A split-root test with L. barbarum seedlings was conducted, and the potassium uptake capacity of LbKAT3 was verified in yeast. A tobacco line overexpressing LbKAT3 was generated and mycorrhizal functions under two potassium concentrations (0.2 and 2 mM K+) were studied. Inoculation of R. irregularis and application of potassium increased the dry weight, and potassium and phosphorus contents of L. barbarum, and increased the colonization rate and arbuscule abundance of R. irregularis. In addition, the expression of LbKAT3 and AQP genes in L. barbarum was upregulated. Inoculation of R. irregularis induced LbPT4, Rir-AQP1, and Rir-AQP2 expression, and application of potassium upregulated the expression of these genes. Inoculation with the AM fungus locally regulated the expression of LbKAT3. Inoculation of R. irregularis improved the growth, and potassium and phosphorus contents, and induced NtPT4, Rir-AQP1, and Rir-AQP2 expression in tobacco overexpressing LbKAT3 under both potassium concentrations. Overexpression of LbKAT3 in tobacco improved the growth, potassium accumulation, and AM colonization, and upregulated the expression of NtPT4 and Rir-AQP1 in mycorrhizal tobacco. The results suggest that LbKAT3 may assist in mycorrhizal potassium uptake, and overexpression of LbKAT3 may promote potassium, phosphorus, and water transport from the AM fungus to tobacco.

Effect of Meteorological Factors, Air Pollutants on Daily Hospital Admissions for Ischemic Heart Disease in Lanzhou, China.

BACKGROUND: Meteorological factors and air pollutants are believed to be associated with cardiovascular disease. Ischemic heart disease (IHD) is a major public health issue worldwide. Few studies have investigated the associations among meteorological factors, air pollutants and IHD daily hospital admissions in Lanzhou, China. METHODS: We conducted a distributed lag non-linear model (DLNM) on the basis of five years data, aiming at disentangling the impact of meteorological factors and air pollutants on IHD hospital admissions. All IHD daily hospital admissions recorded from January 1, 2015 and December 31, 2019 were obtained from three hospitals in Lanzhou, China. Daily air pollutant concentrations and meteorological data were synchronously collected from Gansu Meteorological Administration and Lanzhou Environmental Protection Administration. Stratified analyses were performed by sex and two age-groups. RESULTS: A total of 23555 IHD hospital admissions were recorded, of which 10477 admissions were for coronary artery disease (CAD), 13078 admissions were for acute coronary syndrome (ACS). Our results showed that there was a non-linear (J-shaped) relationship between temperature and IHD hospital admissions. The number of IHD hospital admissions were positively correlated with NO2, O3, humidity and pressure, indicating an increased risk of hospital admissions for IHD under NO2, O3, humidity and pressure exposure. Meanwhile, both extremely low (-12ºC) and high (30ºC) temperature reduced IHD hospital admissions, but the harmful effect increased with the lag time in Lanzhou, China, while the cold effect was more pronounced and long-lasting than the heat effect. Subgroup analysis demonstrated that the risk on CAD hospital admissions increased significantly in female and <65 years of age at -12ºC. CONCLUSION: Our findings added to the growing evidence regarding the potential impact of meteorological factors, air pollutants on policymaking from the perspective of hospital management efficiency.

The sub-molecular characterization identification for cervical cancer.

Background: The efficacy of therapy in cervical cancer (CESC) is blocked by high molecular heterogeneity. Thus, the sub-molecular characterization remains primarily explored for personalizing the treatment of CESC patients. Methods: Datasets with 741 CESC patients were obtained from TCGA and GEO databases. The NMF algorithm, random forest algorithm, and multivariate Cox analysis were utilized to construct a classifier for defining the sub-molecular characterization. Then, the biological characteristics, genomic variations, prognosis, and immune landscape in molecular subtypes were explored. The significance of classifier genes was validated by quantitative Real-Time PCR, cell transfection, cell colony formation assay, wound healing assay, cell proliferation assay, and Western blot. Results: The CESC patients were classified into two subtypes, and the high classifier-score patients with significant differences in ECM-receptor interaction, PI3K-Akt signaling pathway, and MAPK signaling pathway showed a poorer prognosis in OS (p < 0.001), DFI (p = 0.016), PFI (p < 0.001) and DSS (p < 0.001), and with high the M0 Macrophage and resting Mast cells infiltration and low HLA family gene expression. Moreover, the constructed classifier owns a high identified accuracy in the tumor/normal groups (AUC: 0.993), the tumor/CIN1-CIN3 groups (AUC: 0.963), and normal/CIN1-CIN3 groups (AUC: 0.962), and the total prediction performance is better than currently published signatures in CESC (C-index: 0,763). The combined prediction performance further indicated that Nomogram (AUC = 0.837) is superior to the classifier (AUC = 0.835) and Stage (AUC = 0.568), and the C-index of calibration curves is 0.784. The potential biological function of classifier genes indicated that silencing GALNT2 inhibited the cancer cell's proliferation, migration, and colony formation; Conversely, the cancer cell's proliferation, migration, and colony formation were increased after the upregulation of GALNT2. The Epithelial-Mesenchymal Transition Experiment showed that GALNT2 knockdown might reduce the levels of Snail and Vimentin proteins and increase E-cadherin; Conversely, the levels of Snail and Vimentin proteins were increased, E-cadherin was reduced by GALNT2 upregulation. Conclusion: The classifier we constructed may help improve our understanding of subtype characteristics and provide a new strategy for developing CESC therapeutics. Remarkably, GALNT2 may be an option to directly target drivers in CESC cancer therapy.

Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2.

Extracellular signal-regulated kinase 1 and 2 (Erk1/2) signaling has been shown to be involved in brain injury after subarachnoid hemorrhage (SAH). A first-in-human phase I study reported that ravoxertinib hydrochloride (RAH), a novel Erk1/2 inhibitor, has an acceptable safety profile and pharmacodynamic effects. Here, we showed that the level of Erk1/2 phosphorylation (p-Erk1/2) was significantly increased in the cerebrospinal fluid (CSF) of aneurysmal subarachnoid hemorrhage (aSAH) patients who developed poor outcomes. In a rat SAH model that was produced by the intracranial endovascular perforation method, western blot observed that the level of p-Erk1/2 was also increased in the CSF and basal cortex, showing a similar trend with aSAH patients. Immunofluorescence and western blot indicated that RAH treatment (i.c.v injection, 30 min post-SAH) attenuates the SAH-induced increase of p-Erk1/2 at 24 h in rats. RAH treatment can improve experimental SAH-induced long-term sensorimotor and spatial learning deficits that are evaluated by the Morris water maze, rotarod test, foot-fault test, and forelimb placing test. Moreover, RAH treatment attenuates neurobehavioral deficits, the blood-brain barrier damage, and cerebral edema at 72 h after SAH in rats. Furthermore, RAH treatment decreases the SAH-elevated apoptosis-related factor active caspase-3 and the necroptosis-related factor RIPK1 expression at 72 h in rats. Immunofluorescence analysis showed that RAH attenuated neuronal apoptosis but not neuronal necroptosis in the basal cortex at 72 h after SAH in rats. Altogether, our results suggest that RAH improves long-term neurologic deficits through early inhibition of Erk1/2 in experimental SAH.

L-limonene reduces aortic artery atherosclerosis by inhibiting oxidative stress/inflammatory responses in diabetic rats fed high-fat diet.

Atherosclerosis, a leading cause of mortality worldwide, is driven by multiple risk factors such as diabetes. Oxidative stress and inflammation assist interrelated roles in diabetes-accelerated atherosclerosis. Thereby, treatment of diabetic atherosclerosis from an oxidative stress/inflammatory perspective seems to be a more effective modality to prevent and delay plaque formation and progression. This study aimed to evaluate the effects of l-limonene (LMN) on oxidative stress/inflammatory responses in the aortic artery of diabetic atherosclerosis-modeled rats. Male Wistar rats (n = 30, 250-280 g, 12 weeks old) were used to establish a diabetic atherosclerosis model (8 weeks) using high-fat diet/low-dose streptozotocin. LMN (200 mg/kg/day) was administered orally, starting on day 30th before tissue sampling. Plasma lipid profiles, aortic histopathological changes, atherogenic index, aortic artery levels of oxidative stress markers (manganese superoxide dismutase, glutathione, and 8-isoprostane), inflammatory markers (tumor necrosis factor-alpha, interleukin (IL)-6, and IL-10), and expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK)/AMPK, Sirtuin 1 (SIRT1), and p-p65/p65 proteins were evaluated. The administration of LMN to diabetic rats improved lipid profiles, aortic histopathological morphology, and atherogenic index (P < 0.05 to P < 0.001). It also increased enzymatic antioxidant activities, decreased 8-isoprostane level, suppressed inflammatory response, upregulated p-AMPK and SIRT1 proteins, and downregulated p-p65 protein (P < 0.05 to P < 0.01). Inhibiting the AMPK through the administration of compound C significantly abolished or reversed the positive effects of LMN in diabetic rats (P < 0.05 to P < 0.01). LMN treatment had dual anti-oxidative and anti-inflammatory actions against atherosclerosis in the aortic artery of diabetic rats. Atheroprotection by LMN was mediated partly through modulation of AMPK/SIRT1/p65 nuclear factor kappa B signaling pathway. LMN appears to be a promising anti-atherosclerotic modality to improve the quality of life in diabetic patients.

Evaluation of Biomarkers from Peritoneal Fluid as Predictors of Severity for Abdominal Sepsis Patients Following Emergency Laparotomy.

Purpose: Intra-abdominal infection is considered the second most common cause of sepsis and results in localized or diffused inflammation of the peritoneum. The main treatment for abdominal sepsis is an emergency laparotomy for source control. However, surgical trauma also causes inflammation, and patients become susceptible to postoperative complications. Therefore, it is necessary to identify biomarkers that can be used to distinguish sepsis from abdominal infection. This prospective study investigated whether cytokine levels in the peritoneum could predict complications and indicate severity of sepsis following emergency laparotomy. Methods: We prospectively observed 97 patients with abdominal infection admitted to the Intensive Care Unit (ICU). After emergency laparotomy,SEPSIS-3 criteria were used for the diagnosis of sepsis or septic shock. Blood and peritoneal fluid samples were drawn at postoperative admission to the ICU and cytokine concentrations were measured by flow cytometry. Results: Fifty-eight postoperative patients were enrolled. We found significant elevations in the peritoneal concentrations of IL-1ß, IL-6, TNF-α, IL-17, and IL-2 in patients with sepsis or septic shock compared to the patients without sepsis after surgery. Positive correlations between levels of these peritoneal cytokines with APACHE II scores were found: IL-6, in particular, had the highest correlation coefficient of 0.833. Meanwhile, IL-10 in blood, MCP-1 and IL-8 in both blood and peritoneum were simultaneously increased in patients with sepsis and septic shock, and also positively correlated with disease severity. Conclusion: The cytokine storm that occurs in the abdominal cavity after emergency laparotomy may be the main mechanism leading to sepsis. It may be valuable to measure IL-1ß, IL-6, TNF-α,IL-17, IL-2, MCP-1, and IL-8 in the peritoneal fluid, combined with serum IL-10, MCP-1 and IL-8, in a panel of cytokines, to assess the severity of sepsis and predict mortality from abdominal infection after emergency laparotomy.

Chidamide as maintenance after chemotherapy or hematopoietic stem cell transplantation in 27 children with T-cell lymphoblastic leukemia: A real-world prospective study.

Background: The long-term overall survival of children with T-cell acute lymphoblastic leukemia (T-ALL) is limited to approximately 80-85% because of a high incidence of relapse after achieving remission with intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Novel treatment strategies inducing long-term remission are needed to improve the outcome. Histone deacetylase inhibitors (HDACis) have been reported to be effective in a series of T-ALL cases. Preclinical studies suggested that T-ALL cells are sensitive to Chidamide, which is a selective HDACi. Methods: This preliminary clinical study evaluated the efficacy and safety of Chidamide in combination with chemotherapy or post-HSCT for children with T-ALL at a dose of 0.5 mg/kg weight of patient twice per week for at least 6 months. Results: In total, 27 children with a mean age of 7.88 years were included. The high-risk proportion was 66.7%. After a median follow-up period of 37.8 months (9.5-67.9 months), the overall survival and event-free survival in the patients treated with Chidamide were 94.1 and 95.2%, respectively. All patients except two maintained persistent remission with <0.01% blast cells in minimal residual disease. Conclusion: The combination therapy with Chidamide in a case series of T-ALL shows the promising clinical efficacy and good safety in children. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2000030357.

Systematic Identification of Novel Ferroptosis-Associated Multigene Models for Predicting Patient Prognosis Based on Endometrial Cancer.

Objective: Uterine corpus endometrial carcinoma (UCEC) is a frequent epithelial cancer in females. The rate of UCEC occurrence increases year by year and the age is getting younger and younger, which requires more active treatments to improve its prognosis. Ferroptosis is a kind of regulatory cell death that relies on iron and may be triggered by sorafenib, which has been elucidated in several cancers, but the mechanism of ferroptosis-related genes in UCEC has yet to be fully defined and will need more investigation. Methods: The mRNA expression profiles and accompanying clinical data of UCEC patients included in this research were obtained from a publicly available database. We subsequently classified the patients into experimental and training sets. Next, utilizing the least absolute shrinkage and selection operator (LASSO) Cox regression model, we established the multigene features of the TCGA experimental set and verified them in the validation set. Results: Per the findings of our investigation, the TCGA experimental set cohort had four differentially expressed genes (DEGs) that were linked to overall survival (OS). An analysis was conducted using univariate Cox regression (with all variables corrected for P < 0.05). To stratify the patients into two distinct categories, high- and low-risk, a diagnostic model premised on the identified four genes was formulated. In contrast with the low-risk population, the high-risk category exhibited a considerably lower OS (P < 0.0001). The findings of the multivariate Cox regression analysis illustrated that the risk score independently served as a predictor of OS (HR > 1, P < 0.01). The predictive capability of the model was verified by ROC curve analysis. Immune-related pathway enrichment was found using functional analysis, which illustrated that the two risk groups had significantly different immunological statuses. Conclusions: A unique model of genes linked to ferroptosis has the potential to be a treatment option for UCEC and can be utilized for the prognostic prediction of the disease.