Objective To investigate the effects of three mitogen-activated protein kinase (MAPK) inhibitors on the expressions of transforming growth factor-β1 (TGF-β1),α-smooth actin (α-SMA) mRNA and protein in human liver stellate cells (LX-2 cells) activated by sodium arsenite.Methods Cultured in vitro LX-2 cells in the logarithmic growth stage were exposed to sodium arsenite at 0.0 (control),2.5,5.0,10.0,20.0,40.0,80.0 μmol/L for 24 h,respectively,and the cell survival rate was determined by CCK-8 assay.According to the results of the study,LX-2 cells were divided into 5 groups:control group,sodium arsenite group,extracellular signal regulation kinase (ERK) inhibition group,c-Jun amino-terminal kinase (JNK) inhibition group,and p38 inhibition group.LX-2 cells were pre-treated with 10.0 μmol/L ERK,JNK,p38 kinase inhibitors (PD98059,SP600125,SB203580) for 30 min in the 3 inhibition groups,and then 20.0 μmol/L sodium arsenite for 24 h.The control group was not treated with sodium arsenite and inhibitors.Sodium arsenite group was not treated with inhibitors.Then mRNA and protein expression levels of TGF-β1 and α-SMA in LX-2 cells were determined by Western blotting and real-time PCR,respectively.Results The survival rates of LX-2 cells in 5.0,10.0,20.0,40.0,80.0 μmol/L sodium arsenite groups were [(92.35 ± 0.92)％,(84.06 ± 0.84)％,(74.27 ± 0.74)％,(59.57 ± 0.60)％,(27.77 ± 0.23)％],which were significantly lower than that of the control group [(100.00 ± 0.00)％,P ＜ 0.05].It was found that the expressions of TGF-β1,o-SMA mRNA and protein of sodium arsenite group were higher than those of the control group (P ＜ 0.01).The expressions of TGF-β1,α-SMA mRNA and protein of the three inhibition groups were lower than those of the sodium arsenite group (P ＜ 0.05).Conclusions Arsenic exposure can cause abnormally high expressions of TGF-β1,α-SMA mRNA and protein in LX-2 cells.Intervention with three MAPK inhibitors can improve the effects of arsenic induced LX-2 cells activation on the expressions of TGF-β1,α-SMA mRNA and protein.

Objective To evaluate the efficacy and safety of selective brain hypothermia (SBH) in the treatment of neonates with moderate or severe neonatal hypoxic-ischemic encephalopathy (HIE), and the effect of SBH treatment on serum levels of neuron-specific enolase (NSE) and central nervous specific protein S100. Methods A prospective randomized controlled trial was conducted. From January 2015 to June 2017, 42 children with moderate to severe HIE in the neonatal intensive care unit (NICU) of the First Affiliated Hospital of Bengbu Medical College were enrolled, and they were randomly divided into SBH treatment group and routine treatment group after obtaining the consent of the guardian of the children. The children in routine treatment group were given the traditional symptomatic supportive treatment, supplemented by drugs to promote nerve cell growth. On the basis of traditional treatment, the children in the SBH treatment group were given SBH treatment within 6 hours after birth. The nasopharyngeal temperature was maintained at 33.0-34.5 ℃ and the rectal temperature was maintained at 34.5-35.0 ℃. The general clinical data of the two groups including gender, gestational age, birth weight, age, 5-minute neonatal asphyxia score (Apgar score), score for neonatal acute physiology perinatal extension version Ⅱ (SNAPPEⅡ) were collected. The primary outcomes were hospitalized death, severe disability at 15 months of age, neonatal behavioral neurological assessment (NBNA) score at 28 days of age, and Bayley scales of infant development (BSID) score [including mental development index (MDI) score and psychomotor development index (PDI) score] at 15 months of age at follow-up. The secondary outcomes were serum levels of NSE and S100 protein. The occurrences of adverse events in the two groups were recorded. Results Among 42 HIE children, 1 child of severe congenital malformation and 1 child of platelet count (PLT)﹤50×109/L were excluded, and 40 children were enrolled in the study group. During the follow-up period, 2 children of SBH treatment group and 2 children of routine treatment group were lost or the outcome was unknown. Finally, 18 children of each group were enrolled in the analysis. There was no significant difference in the baseline data of gender, gestational age, birth weight, age, 5-minure Apgar score or SNAPPEⅡ score between the two groups, indicating that the baseline data of the two groups were balanced and comparable. The incidence of severe disability in the SBH treatment group was significantly lower than that in the routine treatment group [5.6% (1/18) vs. 44.4% (8/18), P﹤0.05]. There was 1 child death in the routine treatment group and no death in the SBH treatment group. Compared with the routine treatment group, the 28-day NBNA score of the SBH treatment group was increased by 2.9 [95% confidence interval (95%CI) = 1.0-4.8], BSID score at 15 months of age was improved significantly, MDI score was increased by 11.8 (95%CI = 4.3-19.3), and PDI score was increased by 12.4 (95%CI = 2.5-22.3), with significant differences between the two groups (all P﹤0.05). After 3 days of treatment, the serum NSE and S100 protein levels in both groups were significantly decreased as compared with those before treatment [NSE (μg/L): 30.15±15.18 vs. 31.32±14.75, S100 (ng/L): 387.5 (273.3, 573.0) vs. 890.0 (590.5, 1 162.5) in routine treatment group; NSE (μg/L): 29.09±16.22 vs. 32.25±15.43, S100 (ng/L): 402.5 (302.2, 580.5) vs. 842.0 (462.3, 1 200.5) in SBH treatment group, all P﹤0.05]. There was no significant difference in serum NSE or S100 protein level between the two groups (all P﹥0.05). There was no serious adverse event such as arrhythmia, large vein thrombosis or irreducible hypotension in both groups, and there was no significant difference in the incidence of general adverse events such as sinus bradycardia, scleredema, blood glucose disorder, or systemic infection between the two groups [16.7% (3/18) vs. 11.1% (2/18), 5.6% (1/18) vs. 5.6% (1/18), 22.2% (4/18) vs. 11.1% (2/18), 5.6% (1/18) vs. 5.6% (1/18), all P﹥0.05]. Conclusions SBH treatment could significantly increase the NBNA score at 28 days of birth and BSID score at 15 months of age, reduce the incidence of severe disability in moderate and severe HIE children, but it was not be proved that SBH could reduce the mortality. Compared with routine treatment, SBH treatment had no significant superiority on improving the levels of serum NSE and S100 protein, suggesting that SBH could not protect the brain by inhibiting the apoptosis of nerve cells and promoting the repair of nerve cells.

ObjectiveTo investigate the value of ABCR clinical scoring system in guiding repeated transcatheter arterial chemoembolization (TACE) therapy for patients with hepatocellular carcinoma (HCC) and the treatment strategies for patients with an ABCR score of 1-3. MethodsThe patients with HCC who underwent TACE in The First Affiliated Hospital of Soochow University from January 2008 to December 2017 were enrolled. In order to investigate the effect of repeated TACE in patients with different ABCR scores, 229 patients who underwent repeated TACE consecutively (at least twice, without systemic therapy) were enrolled as group A, which was further divided into group A1 with 92 patients (an ABCR score of ≤0), group A2 with 78 patients (an ABCR score of 1-3), and group A3 with 59 patients (an ABCR score of ≥4). In order to investigate the survival time of patients with an ABCR score of 1-3 who received different regimens after first TACE therapy, 118 patients with an ABCR score of 1-3 who received TACE for the first time were enrolled as group B, which was further divided into group B1 with 78 patients (treated with TACE after first TACE therapy), group B2 with 21 patients (treated with TACE combined with sorafenib), and group B3 with 19 patients (treated with sorafenib alone). The survival of the above groups of patients were analyzed. The Fisher’s exact test was used for comparison of categorical data between groups, the Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival time between groups. ResultsThe median survival time was 320 months (95% confidence interval ［CI］: 27.7-36.3) in group A1, 10.3 months (95%CI: 8.4-12.2) in group A2, and 4.6 months (95%CI: 3.7-5.5) in group A3. Group A1 had a better survival time than group A2 (χ2=106.99, P＜0.01), and group A2 had a better survival time than group A3 (χ2=49.66, P＜0.01). The median survival time was 10.3 months (95%CI: 8.4-12.2) in group B1, 14.8 months (95%CI: 7.8-21.8) in group B2, and 6.0 months (95%CI: 4.6-7.4) in group B3, and group B2 had a better survival time than group B1 (χ2=6.80, P＜0.01) and group B3 (χ2=29.89, P＜0.01). ConclusionThe ABCR score has a certain guiding significance for the treatment of HCC patients. Repeated TACE may be considered for patients with an ABCR score of ≤0, while patients with an ABCR score of ≥4 may not benefit from further TACE therapy, and TACE combined with sorafenib might bring maximum benefits to patients with an ABCR score of 1-3.

Objective:To investigate the effects of sodium arsenite (NaAsO 2) on the expression of sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator activated receptor α (PPARα) and fatty acid synthase (FAS) in human liver cells (L-02 cells). Methods:L-02 cells were cultured in vitro, and exposed to NaAsO 2 at 0 (control), 2, 4, 8, 16, 32, 64 and 128 μmol/L for 24 h, respectively, and the cell survival rate was determined by CCK-8 method. And a fitting curve was made to calculate the half inhibitory concentration (IC 50), subsequent experiments were carried out with 0, 1/8, 1/4 and 1/2 of IC 50 as arsenic exposure doses. Glycerol phosphate oxidase-catalase (GPO-PAP) method was used to detect the content of triglyceride (TG) in cells; the mRNA expression levels of SREBP-1c, PPARα and FAS were detected by Real-time PCR; and the protein expression levels of SREBP-1c and PPARα were detected by Western blotting. Results:The cell survival rates of 8, 16, 32, 64 and 128 μmol/L NaAsO 2 groups [(92.000 ± 1.414)%, (91.000 ± 0.000)%, (76.500 ± 0.707)%, (53.000 ± 1.412)%, (47.000 ± 1.412)%] were significantly lower than that of the control group [(100.000 ± 0.000)%, P < 0.01]. The IC 50 was 64 μmol/L, and subsequent experiments were conducted with 0 (control), 8, 16 and 32 μmol/L NaAsO 2, respectively. Compared with the control group [(1.000 ± 0.000) mmol/g prot], TG contents of 8, 16 and 32 μmol/L NaAsO 2 groups [(0.691 ± 0.064), (0.474 ± 0.162), (0.184 ± 0.045) mmol/g prot] were significant decreased ( P < 0.01). Compared with the control group, the mRNA expression levels of SREBP-1c, PPARα, FAS, and the protein expression levels of SREBP-1c and PPARα in NaAsO 2 groups were significantly decreased ( P < 0.01 or < 0.05). Correlation analysis showed that NaAsO 2 content was negatively correlated with TG content, SREBP-1c and PPARα protein expression levels ( r =-0.954,- 0.875,-0.965, P < 0.01). Conclusion:NaAsO 2 can reduce the TG content and the expression of lipid metabolism related genes SREBP-1c, PPARα and FAS in L-02 cells, suggesting that arsenic-induced liver injury can cause lipid metabolism disorders.

Objective:To investigate the efficacy and safety of nasal continuous positive airway pressure (NCPAP) combined with inhalation of pulmonary surfactant (PS) using vibrating mesh nebulizers in the treatment of neonatal respiratory distress syndrome (RDS).Methods:A prospective study was performed on premature infants with RDS admitted to the First Affiliated Hospital of Bengbu Medical College between December 2020 and June 2021. They were randomly assigned into vibrating mesh atomization technology group and intubation-surfactant-extubation (INSURE) technology group. The two groups were treated with NCPAP combined with PS. PS in the vibrating mesh atomization technology group was inhaled into the lungs by the new vibrating mesh atomization technology, while PS in the INSURE group was injected into the lungs by endotracheal tube. The pH value, arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), mechanical ventilation via endotracheal tube (MVET) demand rate, duration of respiratory support, secondary use of PS, complications, and hospital mortality were compared between the two groups. The occurrences of adverse events in the two groups were recorded. Results:A total of 42 preterm infants were finally enrolled, including 20 cases in the vibrating mesh atomization technology group and 22 cases in the INSURE technology group. There were no significant differences in blood gas analysis and PaO 2/FiO 2 before PS administration between the two groups. One hour after PS administration, blood gas analysis and PaO 2/FiO 2 were significantly improved in both groups. Compared with the INSURE technology group, the improvement of PaO 2/FiO 2 was more obvious in the vibrating mesh atomization technology group [mmHg (1 mmHg≈0.133 kPa): 198±34 vs. 173±39, P < 0.05], but no significant difference in pH value or PaCO 2 was found between the two groups. The duration of respiratory support in the vibrating mesh atomization technology group was significantly shorter than that in the INSURE technology group (hours: 96±13 vs. 120±18, P < 0.01), but there was no statistical difference in MVET demand rate [5.0% (1/20) vs. 13.6% (3/22), P > 0.05]. The incidence of periventricular-intraventricular hemorrhage (PVH-IVH) in the vibrating mesh atomization technology group was less than that in the INSURE technology group [0% (0/20) vs. 18.2% (4/22)], but no statistical difference was found ( P > 0.05). No significant differences in the secondary use rate of PS and incidence of bronchopulmonary dysplasia (BPD) or other complications were found between the vibrating mesh atomization technology group and the INSURE technology group [5.0% (1/20) vs. 9.1% (2/22), 5.0% (1/20) vs. 4.5% (1/22), both P > 0.05]. There were no deaths or serious adverse events such as pneumothorax, pulmonary hemorrhage, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in both groups. Conclusion:Compared with the INSURE technique, NCPAP combined with vibrating mesh atomization technology was also effective and safe in the treatment of RDS, which could significantly improve PaO 2/FiO 2 and shorten the duration of respiratory support. Thus, it was worthy of clinical popularization and application.