OTULIN deficiency: focus on innate immune system impairment.

OTULIN deficiency is a complex disease characterized by a wide range of clinical manifestations, including skin rash, joint welling, lipodystrophy to pulmonary abscess, and sepsis shock. This disease is mechanistically linked to mutations in the OTULIN gene, resulting in an immune disorder that compromises the body's ability to effectively combat pathogens and foreign stimuli. The OTULIN gene is responsible for encoding a deubiquitinating enzyme crucial for hydrolyzing Met1-poly Ub chains, and its dysfunction leads to dysregulated immune responses. Patients with OTULIN deficiency often exhibit an increase in monocytes, including neutrophils and macrophages, along with inflammatory clinical features. The onset of symptoms typically occurs at an early age. However, individuals with OTULIN haploinsufficiency are particularly susceptible to life-threatening staphylococcal infections. Currently, the most effective treatment for patients with OTULIN biallelic mutations involves the use of TNF-blocking agents, which target the dysregulated immune response. In conclusion, OTULIN deficiency presents a complex clinical picture with diverse manifestations, attributed to mutations in the OTULIN gene. Understanding the underlying mechanisms is crucial for developing targeted therapeutic interventions to address this challenging condition. Further research into the pathophysiology of OTULIN deficiency is essential for improving clinical management and outcomes for affected individuals.

Pathogens and Pathogenesis in Wheezing Diseases in Children Under 6.

Few studies have comprehensively assessed the roles of cytokine production in wheezing pathogenesis. Therefore, we undertook this study to determine the association between wheezing episodes and cytokines, and to provide further information on this topic. Firstly, we retrospectively collected I176 children, including 122 subjects with first wheezing and 54 subjects with recurrent wheezing, to analyze the etiology and clinical characteristics of children with wheezing diseases. Then, we collected 52 children with wheezing diseases and 25 normal controls to detect the expression of interferon-γ (IFN-γ), interleukin-4 (IL-4), IFN-γ/IL-4, IL-17A, IL-17E, IgE, matrix metalloproteinase-3 (MMP-3), and MMP-9 in serum or plasma. The results showed that boys under 3 years old with history of allergies were more likely to develop wheezing diseases. In our cohort, M. pneumoniae caused a greater proportion of wheezing in children than expected. The expression of IgE [18.80 (13.65-31.00) vs. 17.9 (10.15-21.60)], IL-4 [24.00 (24.00-48.00) vs. 23.00 (9.50-27.00)], IFN-γ [70.59 (41.63-116.46) vs. 49.83 (29.58-81.74)], MMP3 [53.40 (20.02-128.2) vs. 30.90 (13.80-50.95)], MMP9 [148.10 (99.30-276.10) vs. 122.10 (82.20-162.35)], IL-17A [80.55 (54.46-113.08) vs. 61.11 (29.43-93.87)], and IL-17E [1.75 (0.66-2.77) vs. 1.19 (0.488-2.1615)] were significantly increased in the wheezing group (p<0.05) compared to normal controls, while the level of IFN-γ/IL-4 had no significant difference between the two groups (1.24 ± 1.88 vs 0.68 ± 0.74, p>0.05). There was altered cytokine production in children with wheezing diseases which was quite similar to asthma pathogenesis. Sex, age, pathogen infection, and inflammation in our study were also risk factors for wheezing diseases.

A case of brain-lung-thyroid syndrome. / 脑-肺-ç”²çŠ¶è ºç»¼åˆå¾1例.

Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.

Clinical features of invasive fungal disease in children with no underlying disease.

There is limited research into Invasive fungal disease (IFD) in children with no underlying disease. We undertook a retrospective study of children with IFD who did not suffer from another underlying disease, from June 2010 to March 2018 in Changsha, China. Nine children were identified. Eosinophil counts were elevated in six cases. The level of procalcitonin (PCT) was elevated in six cases. Fungal culture was positive in all patients, including eight cases of Cryptococcus neoformans and one case of Candida parapsilosis. 8.33 days following antifungal treatment, the body temperature of the eight patients affected by cryptococcal disease had returned to normal. Our study indicates that the primary pathogen in IFD was Cryptococcus neoformans in children who had no other underlying disease. Eosinophils can be considered to be indicators of cryptococcal infection. IFD in children with no other underlying disease has a satisfactory prognosis.

Impact of sports activity tracking APP on physical fitness of college students / 中国学校卫生

Objective@#To explore the impact of using sports activity tracking APP data recording and social fitness activities on physical and mental health of college students, and to provide theoretical support for using APP to participate in fitness.@*Methods@#A total of 96 students from Xi an International Studies University and Northwest University were recruited and divided into the control group(35 students), the recording group (29 students)and the interactive group(32 students) by using random number table. The recording group and the interactive group used APP for 12 weeks of exercise intervention, while the control group receive no intervention. For any intervention, participants received physical fitness tests before and after the intervention.@*Results@#After the intervention, sit and reach [(19.36±4.55)cm], lung vital capacity [(2 929.93±422.52)mL], sit ups for 1 minute(39.71±8.32) times, standing long jump [(165.14±14.73)cm] in girls of the recording group significantly increased compared with pre intervention [(16.39±6.15)cm, (2 690.93±380.45)mL, (36.14±9.53) times, (157.64±14.93)cm]( t =-3.34,-2.82,-3.52,-4.55, P < 0.05 ), and the BMI of boys[(22.79±2.18)(22.19±2.22)km/m 2] significantly decreased, and pull up of boys[3.50(2.00,4.75), 4.50 (3.25,9.25)times] significantly increased( t=3.90,Z=-2.04,P <0.05). After the intervention, sit and reach and pull up of boys in the interacticve group [(13.08±2.23)cm,6.00(0.00,12.00)times], and sit and reach [(21.43±5.14)cm], lung vital capacity [(3 259.33±562.70)mL], standing long jump [(171.83±19.17)cm] among girls in the interactive group was significantly higher than that before the intervention [(9.78±3.96)cm, 1.00(0.00,7.50)tims, (18.86±6.26)cm, (2 870.94±429.62)mL, ( 162.78 ±17.20)cm] ( t/Z =-4.22,-2.02,-3.43,-2.68,-3.84, P <0.05). After the intervention, compared with the control group, lung vital capacity and standing long jump scores of boys in the recording group were significantly improved, while the scores of sit ups for 1 minute in girls were significantly improved; sit and reach and standing long jump performance of boys in the interactive group were significantly improved; sit and reach and lung vital capacity among girls in the interactive group were significantly improved( P <0.05). Boys in the interactive group showed a significant improvement in sit and reach compared to the recording group ( P <0.05).@*Conclusion@#Using sports activity tracking APP can effectively improve students physical fitness, can promote student participation and persistence in physical activity.

The role of peripheral type 2 innate lymphoid cells in bronchiolitis.

Our aim was to detect type 2 innate lymphoid cells (ILC2s)-related cytokines of infants with bronchiolitis by using Elisa, Liquidchip technology and RT-PCR and investigated its correlation with bronchiolitis. We recruited 26 infants with bronchiolitis and 20 healthy infants as control from Xiangya Hospital. Compared to the control group, the serum levels of interleukin-5 (IL-5) [41.99 (21.11) vs 25.70 (19.64)], IL-9 [27.04 (37.51) vs 8.30 (0.54)], IL-13 [184.05 (132.81) vs 121.75 (176.13)], IL-33 [83.70 (46.69) vs 11.23 (55.31)] and thymic stromal lymphopoietin (TSLP) [31.42 (5.41) vs 28.76 (2.56)] were significantly increased in infants with bronchiolitis (P < 0.05), while the level of IgE had no significant difference between the two groups [19.05 (14.15) vs 14.85 (20.2), P > 0.05]. The mRNA expression of IL-17RB (9.83 ± 0.35 vs 9.19 ± 0.58), TSLP (16.98 ± 2.12 vs 15.07 ± 2.25), retinoid acid receptor related orphan receptor α (7.18 ± 0.71 vs 5.46 ± 1.09) and trans-acting T-cell-specific transcription factor 3 (4.86 ± 0.66 vs 4.19 ± 0.90) were significantly increased in infants with bronchiolitis versus the control group (P < 0.05), while there was no statistical significance for suppression of tumorigenicity 2 (5.59 ± 0.68 vs 5.41 ± 0.87, P > 0.05). Our findings suggested that ILC2s possibly play a specific role in immunopathology of bronchiolitis.

Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children.

BACKGROUND: Asthma is a common chronic lung disease in children. We aimed to determine the associations between stress-induced phosphoprotein 1 (STIP1) and glucocorticoid-induced transcript 1 (GLCCI1) polymorphisms and susceptibility of childhood asthma and inhaled corticosteroid (ICS) response in children. METHODS: A total of 263 Chinese Han asthmatic children were recruited from the Xiangya Hospital, Central South University. Pulmonary function tests were performed before the treatment and 3 months after the treatment. One hundred fifty non-asthmatic children were recruited. Each participant's DNA was extracted from the peripheral blood and Method of MassARRAY was used to genotype the single-nucleotide polymorphisms (SNPs). RESULTS: STIP1 rs2236647 wild-type homozygote (CC) was associated with increased asthma risk of children (OR = 1.858, 95% CI:1.205-2.864), but not associated with the ICS response. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms were not associated with the risk of childhood asthma. However, rs37969 mutant genotypes (TT/GT) were significantly associated with less improvement in PD20 (p = 0.028). We also found significant associations between rs37969, rs37972 and rs37973 mutant genotypes and less improvement in maximal midexpiratory flow (MMEF) after ICS treatment for 3 months (p = 0.036, p = 0.010 and p = 0.003, respectively). CONCLUSIONS: STIP1 rs2236647 was associated with asthma risk of children and GLCCI1 rs37969 mutant genotypes were associated with less improvement in airway hyper-responsiveness. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms might be associated with pulmonary function in childhood asthma patients after ICS treatment.

[Hereditary hemorrhagic telangiectasia: a report of two cases].

This article reports two children with hereditary hemorrhagic telangiectasia (HHT). Patient 1 was a boy aged 12 years and was admitted due to intermittent cough and wheezing for more than 10 years. This boy and his mother and grandmother had a history of epistaxis. The boy had a history of the rupture of cerebral arteriovenous malformations. Gene detection showed a heterozygous mutation, c.277C>T(p.Arg93*), in the ENG gene. Patient 2 was a girl aged 13 years and was admitted due to cyanosis of lips for more than 1 year. The girl had a history of recurrent epistaxis and the manifestations of severe decline in pulmonary diffuse function, pulmonary hypertension, dilation of blood vessels at the distal end of lungs, and small arteriovenous communications in both lungs. Children with HHT often lack typical respiratory symptoms, which may lead to missed diagnosis and misdiagnosis in the early stage. Pulmonary computed tomography or right cardiac acoustic contrast can help with the diagnosis of HHT, and gene detection can improve the early diagnostic rate of this disease.

[Acute fever with rash, necrosis, and bullae in both lower extremities in a 12-year-old girl].

A girl, aged 12 years, was admitted due to fever and rash for 3 days. The child developed recurrent high fever and rash on both lower extremities 3 days before, and the rash on left lower extremity quickly merged into a patch within 24 hours, with hemorrhage and necrosis in black and purple, large vesicles, and blisters in the center. Laboratory examination showed a reduction in platelet count and significant increases in fibrinogen and D-dimer during the course of the disease. The child was diagnosed with purpura flulminans. She was given meropenem combined with linezolid for anti-infection, injection of gamma globulin for immunoregulation, and low-molecular-weight heparin for anticoagulation. The fluid in the rash blisters was drawn and the wound was treated to prevent infection. The child's temperature returned to normal, with improvement in gangrene. She was discharged after platelet count, fibrinogen, and D-dimer had returned to normal. Purpura fulminans is a rare thrombotic hemorrhagic disease with rapid progression and is commonly seen in children. Without timely treatment, it may cause severe sequelae with high disability and mortality rates. Anti-infection, correction of coagulation function, and local management of gangrene skin are of great importance during treatment.

[Cyanosis for more than 4 years in a girl aged 4 years and 3 months].

A girl, aged 4 years and 3 months, presented with cyanosis of the lips shortly after birth. She then experienced shortness of breath after activity 1 year ago and acrocyanosis 3 months ago, with obvious acropachy and toe deformity. Laboratory examinations revealed an increase in hemoglobin (178 g/L) and a reduction in arterial partial pressure of oxygen (37.7 mm Hg). Plain and contrast-enhanced CT scans of the lungs showed a large area of dense shadow and multiple nodules with clear boundaries in the right lower lung, as well as thickening of the arteries and dilatation of the veins in the right lower lung. Magnetic resonance angiography of the pulmonary artery showed large arteriovenous malformation in the lung. The child was diagnosed with congenital pulmonary arteriovenous fistula and was given interventional embolization of the pulmonary arterial fistula. The child was followed up at 3 months after surgery. The symptoms of shortness of breath and cyanosis disappeared, and activity tolerance, heart rate, hemoglobin, red blood cell count, and transcutaneous oxygen saturation all returned to normal.

[Clinical features of neuroendocrine cell hyperplasia of infancy].

OBJECTIVE: To study the clinical features of neuroendocrine cell hyperplasia of infancy (NEHI) in order to provide a basis for the management of diagnosis, treatment and prognosis of children with NEHI. METHODS: A retrospective analysis was performed for the clinical data of seven children with NEHI who were diagnosed and treated from January 2014 to March 2016. RESULTS: Among the seven children with NEHI, there were five boys and two girls. Two children experienced tachypnea since the neonatal period, and five children developed respiratory tract symptoms within 1-6 months after birth. Of the 7 children, 6 had pulmonary crackles, 4 had hypoxemia, and 3 had gastroesophageal reflux. Lung high-resolution CT (HRCT) showed ground-glass opacities in the central region of the lungs in all children, which involved at least two lung lobes. Of the 7 children, 2 had the involvement of more than 4 lobes and 6 had air trapping. All 7 children had an improvement in clinical symptoms after two years of age. One child achieved clinical and CT remission. Four children achieved clinical remission, but still with CT changes. CONCLUSIONS: NEHI often occurs in infancy, with the major clinical manifestations of persistent tachypnea, pulmonary crackles, and hypoxemia. The children with NEHI often present ground-glass opacities in the central region of the lungs and air trapping on HRCT. There is no specific treatment for this disease and most cases have a good prognosis.

Gene polymorphisms in VEGFA and COL2A1 are associated with response to inhaled corticosteroids in children with asthma.

Aim: The purpose of this study was to investigate the involvement of single-nucleotide polymorphisms in VEGFA, TBX21 and COL2A1 in the response to inhaled corticosteroids in asthmatic children. Subjects & methods: Children with mild-to-moderate asthma were enrolled in the study. The SEQUENOM MassARRAY method was used to sequence 27 SNP genotypes. By ranking the data from smallest to largest, we could infer whether the change in distribution of forced expiratory volume in one second/forced vital capcacity (FEV1/FVC) and fractional exhaled nitric oxide differed between genotype groups. Results:VEGFA rs3025039 T allele carriers had a smaller change in FEV1 than CC carriers (p = 0.040), and in COL2A1 rs3809324, the frequency of T allele carriers was lower than that of GG carriers (p = 0.048). rs3025039 was also associated with changes in FEV1/FVC (p = 0.016). Conclusion:VEGFA and COL2A1 polymorphisms are significantly associated with the response to inhaled corticosteroids in asthmatic children.

[Liver dysfunction for 8 years with hypertension for 1 week in an 8-year-old girl].

A girl, aged 8 years, developed jaundice and liver dysfunction in the neonatal period, with congenital glaucoma diagnosed on day 5 after birth, hypertension and unusual facies (broad forehead, hypertelorism and deep-set eyes). Cholestasis was the main type of liver dysfunction. Cardiac macrovascular CTA showed stenosis at the abdominal aorta and the beginning of the bilateral renal arteries. Whole exon sequencing revealed a heterozygous frameshift mutation, c.1485delC (absence of cytosine), in exon 12 of the JAG1gene. The girl was diagnosed with Alagille syndrome and was given transaminase-lowering, cholagogic and antihypertensive treatment with multiple drugs. There were significant reductions in serum levels of alanine aminotransferase, aspartate aminotransferase and total bile acid, but blood pressure fluctuated between 102-140 mm Hg/53-89 mm Hg. After renal artery angiography and balloon dilatation angioplasty, the girl was given oral administration of antihypertensive drugs, and blood pressure was controlled at a level of 110-120 mm Hg/60-80 mm Hg. The rare disease Alagille syndrome should be considered when a child has refractory hypertension with the involvement of multiple systems, especially liver dysfunction with cholestasis as the main manifestation. Genetic causes should be analyzed for a early diagnosis.

IL-17A and GDF15 are able to induce epithelial-mesenchymal transition of lung epithelial cells in response to cigarette smoke.

Smoking is one of the primary causes of chronic obstructive pulmonary disease (COPD). Sustained active epithelial-mesenchymal transition (EMT) in COPD may explain the core pathophysiology of airway fibrosis and why lung cancer is so common among smokers. Interleukin (IL)-17A and growth/differentiation factor (GDF)15 have been reported to be biomarkers of COPD; however, the role of IL-17A and GDF15 in EMT remains unclear. The aim of the present study was to investigate the role of IL-17A and GDF15 in the pathogenesis of COPD. It was demonstrated that IL-17A and GDF15 are upregulated in patients with COPD, particularly those with a history of smoking. The results also revealed that IL-17A and GDF15 expression was negatively correlated with the epithelial marker epithelial-cadherin and positively correlated with the mesenchymal marker vimentin. Furthermore, treatment with cigarette smoke extract or IL-17A induced GDF15 expression. Combined treatment with IL-17A and GDF15 induced EMT in human small epithelial HSAEpiC cells in vitro. Collectively, the results of the present study suggest that IL-17A and GDF15-induced EMT serves an important role in the pathology of COPD.

Knockdown of SALL4 overcomes cisplatin-resistance through AKT/mTOR signaling in lung cancer cells.

Drug resistance is an important factor for the poor prognosis of non-small cell lung cancer (NSCLC). Sal-like protein 4 (Sall4) is a stem cell marker, and plays a role in maintaining self-renewal. Previous studies have demonstrated that Sall4 may be a candidate for use as support in the diagnosis of lung cancer, and may also represent a therapeutic target. However, the role of Sall4 on drug resistance of lung cancer cells and the mechanism by which Sall4 regulates the sensitivity of lung cancer cells to cisplatin (DDP) remains unknown. In this study, we aim to investigate whether knockdown of Sall4 by siRNA can enhance the apoptosis induced by cisplatin in lung cancer cells. We here reported that the expression of Sall4 was dramatically upregulated in cisplatin-resistant A549 cells compared with the parental cells. Knockdown of Sall4 by siRNA in cisplatin-resistant A549 cells reduced the IC50 compared with the parental cells. In addition, knockdown of Sall4 significantly inhibited cell proliferation, induced apoptosis and invasion cisplatin-resistant A549 cells through AKT/mTOR signaling. Our findings demonstrate that Sall4 is an essential regulator in cisplatin-induced apoptosis, and knockdown of Sall4 may restore cisplatin sensitivity in acquired resistant cells. Thus, our study provides an effective therapeutic strategy for NSCLC treatment.

[Analysis for the effect of different regimens on ocular myasthenia gravis in children].

OBJECTIVE: To evaluate the efficacy, recurrent risk factors and transferable ratio of treatments with 3 different regiments on children with systematic myasthenia gravis (MG).
 Methods: The data of 104 children with ocular MG from June 2010 to March 2014 were collected from Department of Pediatric Neurology of Xiangya Hospital and they were retrospectively studied. The patients were divided into 3 groups: a methylprednisolone group (n=44), a prednisone group (n=48) and a bromine pyridostigmine group (n=12). Evaluative system from American MG foundation was used to evaluate the efficacy of treatment and the ratio of ocular MG transformed into systematic MG.
 Results: The efficacy in the methylprednisolone group was better than that in the prednisone group, and both of them were better than that in the bromine pyridostigmine group (both P<0.05).Methylprednisolone, prednisone combined with bromine pyridostigmine could reach a better long-term efficacy in children with ocular MG. Early treatment with glucocorticoid could reduce clinical relapse.
 Conclusion: A treatment with high-dose methylprednisolone pulse can improve early clinical remission in children with ocular MG. However, there is a similar efficacy in the long run of different glucocorticoid therapeutic regiments. A relatively order onset age, infection and thyroid dysfunction are recurrent risk factors in children with ocular MG.

[A case of Gitelman syndrome with physical retardation].

Gitelman syndrome is a rare disease. It is easy to be misdiagnosed and missed diagnosis due to the diverse clinical symptoms. A girl with long-term hypokalemia, who presented with intermittent pain of lower limb muscle and physical retardation, was treated in Xiangya Hospital, Central South University. Laboratory examination confirmed the severe hypokalemia and metabolic alkalosis. Gene sequencing indicated SLC12A3 gene mutation and the patient was finally diagnosed as Gitelman syndrome. Patients with chronic hypokalemia and metabolic alkalosis need to conduct gene sequencing to confirm the diagnosis. Gene therapy is expected to be the most effective treatment for this disease.

The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma.

INTRODUCTION: Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Recurrent respiratory tract infections in young children, especially viral infections, are the major cause of acute asthmatic exacerbations and contribute to development of asthma. Bacterial extracts have been used to improve the immune defenses of the respiratory tract. However, seldom studies have examined the effect of bacterial lysates on childhood asthma. In this study, we examined whether bacterial lysates (OM-85) will improve symptoms of asthmatic mice via modulation of the immune response. METHODS: Asthmatic mice models were established with OVA challenge and treated with oral administration of Broncho-Vaxom (OM-85). Next, infiltrations of inflammatory cells including eosinophil and neutrophils were examined. Pulmonary tissues in asthmatic mice models were analyzed by hematoxylin and eosin (HE) staining. The levels of Th1/Th2-typed cytokines in bronchoalveolar lavage fluid (BALF) of asthmatic mice models were examined by enzyme-linked immunosorbent assay. RESULTS: Compared to control group, we found significant reduction of airway wall thickness, luminal stenosis, and mucus plug formation in asthmatic mice models after oral administration of OM-85. The infiltrations of eosinophil were also significantly decreased in BALF in asthmatic mice models. Oral administration of OM-85 was shown to suppress Th2-type cytokine levels. CONCLUSION: Our findings provide evidence that oral administration of OM-85 is capable of attenuating airway inflammation in asthmatic mice models. Oral administration of OM-85 may have a positive impact in terms of asthma severity.

Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.