BACKGROUND:Ferroptosis is a mode of programmed cell death distinct from apoptosis,necrosis,and other novel cellular deaths,which occurs mainly due to accumulated lipid peroxidation.Ferroptosis has been shown to be involved in the pathological process following subarachnoid hemorrhage.Baicalein,serving as an adept sequestered of iron,evinces its prowess by quelling lipid peroxidative cascades.Nonetheless,the enigma lingers as to whether baicalein possesses the capacity to ameliorate neuronal ferroptosis,elicited in the wake of early brain injury after subarachnoid hemorrhage. OBJECTIVE:To investigate the effect and mechanism of baicalein on neuronal ferroptosis after subarachnoid hemorrhage. METHODS:Primary neuronal cells were extracted from C57BL/6L fetal mice at 16-17 days of gestation.Hemoglobin was used to stimulate primary neuronal cells to simulate an in vitro subarachnoid hemorrhage model.The viability of primary neuronal cells treated with baicalein at concentrations of 5,15,25,50,and 100 μmol/L for 24 hours was detected by CCK-8 assay to determine the optimal concentration of baicalein.Primary neuronal cells were divided into control group,hemoglobin group,and hemoglobin+baicalein group.The levels of reactive oxygen species and malondialdehyde in cells were detected by kits.The mRNA expressions of ferroptosis-related markers PTGS2,SLC7A11,and glutathione peroxidase 4 were detected by RT-PCR.The primary neuronal cells were further divided into control group,SLC7A11 inhibitor Erastin group,hemoglobin group,hemoglobin+baicalein group,and hemoglobin+baicalein+Erastin group.The expression of the ferroptosis related markers SLC7A11 and glutathione peroxidase 4 was detected by western blot assay. RESULTS AND CONCLUSION:(1)Baicalein(25 μmol/L)was selected as the following experimental concentration.(2)Compared with the hemoglobin group,the level of malondialdehyde and the level of reactive oxygen species were significantly decreased(P<0.05)in the hemoglobin+baicalein group.(3)Compared with the hemoglobin group,the mRNA expression of PTGS2 significantly decreased,and the mRNA expression of SLC7A11 and glutathione peroxidase 4 significantly increased(P<0.000 1)in the hemoglobin+baicalein group.(4)SLC7A11 inhibitor Erastin could reverse the baicalin-improved ferroptosis effect to a certain extent(P<0.05).(5)The results showed that baicalein could alleviate the ferroptosis of neuronal cells after subarachnoid hemorrhage through the SLC7A11/GPX4 pathway.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

BACKGROUND:The pituitary gland is an important endocrine organ in the body.Certain diseases can cause damage to the pituitary gland,such as pituitary adenoma and abnormal hormone secretion.Pituitary stem cells,due to their self-renewal and multi-directional differentiation potential,are expected to become a new therapeutic approach for repairing damaged pituitary glands. OBJECTIVE:To isolate and culture pituitary stem cells using the suspension cell ball culture method and identify their proliferation and differentiation ability. METHODS:Pituitary stem cells were isolated and cultured from the pituitary gland of newborn New Zealand white rabbits using the suspension cell ball culture method,and their morphological characteristics were observed.Immunofluorescence cytochemistry was used to detect the expression of pituitary stem cell markers SOX2 and Nestin.EdU labeling method was utilized to detect the proliferative ability of pituitary stem cells.After adherent and induced differentiation,the hormone levels in the culture medium were detected by ELISA. RESULTS AND CONCLUSION:Pituitary stem cell spheres could be successfully isolated by the suspension cell ball culture method,with strong proliferative ability.Positive expression of stem cell-specific markers SOX2 and Nestin was found in the cultured cells.After induction and differentiation,adrenocorticotropic hormone,thyroid hormone,growth hormone,luteinizing hormone,follicle-stimulating hormone,and prolactin levels significantly increased in the medium(P<0.001),with strong differentiation ability.

Objective To investigate the regulatory effect of Xuebijing injection on inflammatory reaction during the preservation of isolated empty beating pig hearts with extracorporeal membrane oxygenation.Methods Twelve healthy Guangxi Bama miniature pigs were randomly divided into the Xuebijing group(n=6)and normal saline group(n=6).After the models were established in the Xuebijing group,Xuebijing injection was given at a dose of 5 mL/h through micropump in membrane oxygenator.In the normal saline group,an equivalent amount of 0.9％sodium chloride injection was pumped.Continuous pumping was performed for 8 h in both groups.The time of cardiac resuscitation and perfusion pressure,heart rate,perfusion flow rate after 8 h preservation were recorded in two groups.Pathological and ultrastructural changes of myocardial tissues in the left ventricular wall of hearts with cardiac arrest were observed after 8 h preservation.Serum levels of myocardial injury markers and inflammatory cytokines were detected in two groups at the beginning(T0),2 h(T2),4 h(T4),6 h(T6)and 8 h(T8)after model establishment,respectively.The expression levels of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate specific proteinase-1(Caspase-1),apoptosis-associated speck-like protein containing a CARD(ASC)messenger RNA(mRNA)in myocardial tissues were measured at T0,T2,T4,T6 and T8,respectively.Results There were no significant differences in the time of cardiac resuscitation and perfusion pressure,heart rate,perfusion flow rate after 8 h preservation between two groups(all P＞0.05).Compared with the normal saline group,the levels of lactate dehydrogenase(LDH)at T4,creatine kinase(CK),LDH and α-hydroxybutyrate dehydrogenase(α-HBDH)at T6 and T8,tumor necrosis factor(TNF)-α at T4,T6 and T8,and interleukin(IL)-6,IL-18 and IL-1 β at T0,T2,T4,T6 and T8 were lower,and the mRNA relative expression levels of NLRP3 and Caspase-1 at T2,T4 and T6,and Caspase-1 and ASC at T8 were lower in the Xuebijing group,respectively(all P＜0.05).Hematoxylin-eosin staining and transmission electron microscopy showed that the degree of myocardial injury in the Xuebijing group was slighter than that in the normal saline group.Conclusions Xuebijing injection may effectively mitigate inflammatory response and exert certain myocardial protection effect during the ECMO preservation of isolated empty beating pig hearts.

Objective To study the mechanism of antidepressant effect of Baihe Zhimu decoction based on NLRP1 inflammasome.Methods A chronic unpredictable mild stress(CUMS)induced depression mouse model was constructed.C57BL/6J mice were randomly divided into a control group,CUMS group,low-dose Baihe Zhimu decoction group,high-dose Baihe Zhimu decoction group,and MDP group(NLRP1 activator).After continuous administration for 4 weeks,the behavioral characteristic of mice was investigated.The levels of mice hippocampal inflammatory factors IL-1β、IL-6,TNF-α,and neurotransmitters 5-HT,NE,and DA were detected by ELISA.The expression of inflammasome related proteins NLRP1,ASC,and caspase-1,as well as related proteins in BDNF/TrkB and ERK/AKT/mTOR signaling pathway were detected by Western blot.Immunofluorescence was used to detect changes in BDNF expression in the hippocampus of mice.Results Baihe Zhimu decoction inhibited the activation of NLRP1 inflammasomes in the hippocampus of CUMS mice,improved their behavioral characteristics,increased the level of neurotransmitters in the hippocampus,and reduced the inflammatory response.The NLRP1 activator MDP reversed the above effects of Baihe Zhimu decoction.Baihe Zhimu decoction increased BDNF,TrkB expression,and phosphorylation levels of ERK,AKT,and mTOR proteins,which could be reversed by MDP.Conclusion Baihe Zhimu decoction improved depression like behavior in CUMS mice by inhibiting NLRP1 inflammasome activation and hippocampal neuroinflammatory response,and thereby activating BDNF/TrkB and ERK/AKT/mTOR signaling pathway.

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide.For lung adenocarcinoma,identifying specific gene mutations,fusions,and giving corresponding targeted drugs can greatly improve the survival time of the patients.Among them,anaplastic lymphoma kinase(ALK)fusion occurs in 3％-7％of non-small cell lung cancer(NSCLC).In clinical practice,a variety of detection methods can be used to determine the ALK fusion status,but false negative test results are possible.This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adeno-carcinoma,judged the ALK fusion status by various detection methods.Among them,immunohistochemistry(IHC)(Ventana D5F3),RNA based next-generation sequencing(RNA-based NGS)confirmed positive echinoderm microtubule associated protein like 4(EML4)-ALK fusion,while DNA-based NGS was negative.This paper analyzed the detection methods of ALK fusion,in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment.

Lung cancer is a major cause of cancer-related mortality worldwide. Among patients with non-small cell lung cancer (NSCLC), approximately 3%-7% harbor anaplastic lymphoma kinase (ALK) gene fusions. In recent years, multiple tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with metastatic ALK-positive NSCLC. However, disease progression due to resistance remains a challenge. This article retrospectively analyzes a case of advanced lung adenocarcinoma with the echinoderm microtubule associated protein like 4 (EML4)-ALK fusion variant 3 (V3). The patient developed resistance to Lorlatinib treatment accompanied by mesenchymal-epithelial transition factor (MET) amplification. Effective tumor control was achieved with the combined use of Crizotinib and Lorlatinib, providing a valuable reference for further exploration of treatment strategies following resistance to ALK-TKIs in clinical practice.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/genetics* ; Aminopyridines/therapeutic use* ; Crizotinib/therapeutic use* ; Drug Resistance, Neoplasm/drug effects* ; Lactams/therapeutic use* ; Lung Neoplasms/genetics* ; Oncogene Proteins, Fusion/metabolism* ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/metabolism* ; Pyrazoles/therapeutic use*

ObjectiveTo investigate the status of health literacy of child rearing among caregivers of 0‒3 year-old children and analyze its determinants in Minhang District， Shanghai to provide scientific evidence for further promoting health literacy of caregivers. MethodsThe caregivers of 0‒3 year-old children were randomly selected and investigated using a questionnaire of health literacy in 13 community health care centers of Minhang District from March 2020 to April 2021. ResultsA total of 2819 valid questionnaires were collected. The total score of health literacy of child rearing for caregivers were 159.2±23.1 （full score being 200.0）. The score of physical health literacy and mental health literacy were 80.0±10.2 and 79.1±15.1， respectively （full score being 100.0）. The proportions of health literacy in the caregivers were： scarce 3.1%， insufficient 7.6%， good 47.2%， and excellent 42.1%. The multivariate ordinal Logistic regression model showed the following were independent determinants： always （OR=5.90） or often （OR=3.55） choosing information from professional approach like hospital to guide children rearing，mother （OR=4.98） or father （OR=3.95） being caregivers， easy access to children rearing information （OR=4.50）， mother education degree being master and above （OR=3.10） or junior college， undergraduate （OR=2.14）， father education degree being junior college， undergraduate （OR=1.59） or master and above （OR=1.53）， single child （OR=1.37）， household registration being Shanghai （OR=1.37）. All caregivers with the above factors showed more superior health literacy. ConclusionThe level of health literacy of child rearing among caregivers of 0‒3 year-old children in Minhang District has a good level of health literacy. Targeted health education should be strengthened for caregivers of children in the future.

Objectives To explore the nutritional status of vitamin A in healthy children and children with respiratory infection symptoms, and its correlation with hemoglobin levels. Methods Health children who lived in Beijing for over half year during December 2014 to August 2015 were included. Serum retinol and peripheral blood hemoglobin were measured. The relationship of vitamin A nutritional status with age, respiratory tract infection and anemia were analyzed. Results A total of 1742 children (1056 males and 686 females) with a median age of 3.1 years (6 months~17 years) were enrolled. 202 children had respiratory tract infection and 1540 children didn't have respiratory tract infection when visiting. The median serum retinol level was 0.29 mg/L (0.25~0.33 mg/L) in all children. The level of retinol in children with respiratory tract symptoms was significantly lower than that in children without respiratory symptoms (P<0.001). The prevalence of subclinical vitamin A deficiency and suspected subclinical deficiency were 5.8% and 47.9% respectively. The prevalence of both the subclinical and suspected subclinical vitamin A deficiency ratios were >50% in children under 9-year-old. The prevalence of subclinical vitamin A deficiency and suspected subclinical deficiency among different age groups were statistically different (P<0.001). The incidence of anemia in subclinical vitamin A deficiency, suspected subclinical deficiency children and normal children were 3.9%, 8.7%, and 10.8% respectively, and The differences were statistically significant (P<0.01). Serum retinol and hemoglobin concentrations were positively correlated with age (r=0.179 or 0.571, P all < 0.001). Furthermore, serum retinol was positively correlated with the concentration of hemoglobin (r=0.244, P<0.001). Conclusions Serum retinol level in children with respiratory infection is lower than that in healthy children. Vitamin A deficiency was associated with anemia.

Objective To investigate the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the factors influencing the related changes in cognitive ability.Methods Seventy-five subjects with mild cognitive impairment (the MCI group),32 with Alzheimer's disease (the AD group) and 17 others with normal cognition (the NC group) were recruited.The Montreal Cognitive Assessment (MOCA) and the Mini-mental State Examination (MMSE) were used to assess their cognitive ability.At the same time,relevant clinical information such as their general condition and past history of disease were recorded.The subjects were followed up for 20 months on average to evaluate their annual rates of progression (APRs),and logistic regression was used to highlight any influencing factors.Results By the end of the follow-up,9 of the 75 MCI subjects had progressed to AD,with an APR of 5.25％.Thirteen cases had recovered normal cognitive functioning (97.6 per 1,000 person-years).Also,2 cases in the NC group (11.76％) developed MCI (69.1 per 1,000 person-years),but none of them had yet progressed to AD.Both hyperlipidemia and a body mass index (BMI) lower than 24 kg/m2 significantly predicted the deterioration of cognitive functioning.Heart disease was significantly correlated with cognitive improvement,and selfmanagement of cognitive function was also a significant protective factor.Conclusions Patients with MCI are at greater risk of developing AD than normal persons.Prevention and early treatment of hyperlipidemia as well as maintaining a normal BMI may delay the deterioration of cognitive functioning.Self-management of cognitive function can improve cognition.