[Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma].

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

[Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma].

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.

[Clinical characteristics and prognosis of seizures in 75 children with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION: Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.

MiR-140 protects against myocardial ischemia-reperfusion injury by regulating NF-κB pathway.

OBJECTIVE: The aim of this study was to investigate the effect of micro ribonucleic acid (miR)-140 on rats with myocardial ischemia-reperfusion injury (MIRI) through regulating the nuclear factor-κB (NF-κB) pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including sham group (n=12), model group (n=12) and miR-140 mimics group (n=12). In sham group, only thoracotomy was performed without ischemia-reperfusion. In model group, the MIRI model was first established, followed by intervention using normal saline. In miR-140 mimics group, the MIRI model was first established as well, followed by intervention using miR-140 mimics. The content of serum creatine kinase (CK) and lactate dehydrogenase (LDH) was detected, and the morphology of myocardial tissues was observed via hematoxylin-eosin (HE) staining. Meanwhile, the relative protein expression of NF-κB was determined using Western blotting. Quantitative polymerase chain reaction (qPCR) was conducted to evaluate the expression of miR-140. The content of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) was determined via enzyme-linked immunosorbent assay (ELISA). Furthermore, cell apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The content of serum CK and LDH rose significantly in model group and miR-140 mimics group when compared with sham group (p<0.05). However, it declined significantly in miR-140 mimics group compared with model group (p<0.05). HE staining results showed that there were no obvious abnormalities in the morphology of myocardial tissues in sham group. However, there were injury and inflammatory infiltration in myocardial tissues in model group. Meanwhile, the structure and morphology of myocardial tissues were improved in miR-140 mimics group compared with those in model group. Western blotting revealed that the relative protein expression of NF-κB was evidently higher in model group and miR-140 mimics group than sham group (p<0.05). However, it was remarkably lower in miR-140 mimics group than that in model group (p<0.05). QPCR results demonstrated that the relative expression of miR-140 in model group and miR-140 mimics group was obviously lower than sham group (p<0.05). However, a markedly higher expression of miR-140 was observed in miR-140 mimics group than model group (p<0.05). ELISA results indicated that model group and miR-140 mimics group had remarkably higher content of IL-1ß and TNF-α than sham group (p<0.05). However, miR-140 mimics group had remarkably lower content of IL-1ß and TNF-α than model group (p<0.05). TUNEL assay indicated that the apoptosis rate increased obviously in model group and miR-140 mimics group compared with sham group (p<0.05). However, it declined significantly in miR-140 mimics group compared with model group (p<0.05). CONCLUSIONS: MiR-140 suppresses inflammation and apoptosis in myocardial tissues of MIRI rats through inhibiting the NF-κB signaling pathway, thereby exerting a cardioprotective effect.

[Interpretation for the group standards in technical specification for health risk investigation of central air conditioning ventilation system during coronavirus disease 2019 epidemic].

The central air conditioning ventilation system plays an important role in the air circulation of buildings such as centralized isolation medical observation points and general public buildings. In order to meet the requirements of COVID-19 epidemic prevention and control, Beijing Preventive Medicine Association organized Beijing CDC and other professional institutes to write up the group standard entitled "Technical specification for health risk investigation of central air conditioning ventilation system during the COVID-19 epidemic (T/BPMA 0006-2020)" . According to the particularity of central air conditioning ventilation system risk control during the outbreak of similar respiratory infectious diseases, based on current laws and regulations and the principle of scientific, practical, consistency and normative, 8 key points of risk investigations were summarized, which were the location of fresh air outlet, air conditioning mode, air return mode, air system, air distribution, fresh air volume, exhaust and air conditioner components. The contents, process, method, data analysis and conclusion of the investigation implementation were also defined and unified. It could standardize and guide institutions such as disease control and health supervision to carry out relevant risk managements, and provided solutions and technical supports for such major public health emergencies in city operations.

Protective effect of overexpression of PrxII on H2O2-induced cardiomyocyte injury.

OBJECTIVE: Oxidative stress is one of the main factors leading to myocardial cell damage, and the redox imbalance promotes apoptosis. Therefore, the purpose of this study was to explore the protective effect of PrxII on H2O2-induced H9c2 cell injury. MATERIALS AND METHODS: The overexpressed PrxII cell model was constructed by virus. The H9c2 cells were treated with H2O2, and the supernatant and cells were collected. Then, the chymotrypsin-like activity, caspase-like activity, and trypsin-like activity were detected by the kit, and the expressions of P21, P27, and P53 were detected by the ELISA method. Finally, the expressions of antioxidant factors, apoptosis-related factors, and AMPK/Sirt1 signaling pathway were detected by Western blot and Real-time polymerase chain reaction (PCR). RESULTS: Overexpression of PrxII inhibited the decrease of enzyme activity induced by H2O2, promoted the expressions of anti-oxidation factors GPX1, GPX2, and GSX, and inhibited the expressions of apoptosis-related factors P21, P27, and P53, and activated AMPK/Sirt1 pathway. CONCLUSIONS: Overexpression of PrxII can activate the AMPK/Sirt1 pathway, thereby inhibiting H2O2-induced oxidative stress and slowing apoptosis.

[Chimeric antigen receptors T cells for treatment of 48 relapsed or refractory acute lymphoblastic leukemia children: long term follow-up outcomes].

Objective: To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors. Methods: Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis. Results: No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ2=4.968, P=0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate (P<0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% (RR=3.433, 95% CI 1.333-8.844, P=0.011) and not bridge to HSCT (RR=4.996, 95% CI 1.852-13.474, P=0.001) were the independent risk factors. Conclusion: The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.

[Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia].

Objective: To analyze the clinical outcome and the prognostic factor in pediatric patients with core binding factor-acute myeloid leukemia (CBF-AML). Methods: A total of 121 newly diagnosed pediatric CBF-AML patients enrolled from Aug. 2005 to Sep. 2017 were retrospectively reviewed. Cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method and prognostic factors were evaluated by Cox regression with SPSS. Results: Of the 121 patients, 120 patients were assessed for bone marrow remission after induction chemotherapy. 100 cases (83.3%) achieved complete remission (CR) after the first course of chemotherapy. 119 cases (99.2%) achieved CR after the second course of chemotherapy. Of the 121 patients, 13 patients (10.7%) had recurrence with the median interval of recurrence as 13.8 months (3.7 to 58.8 months). 17 patients (14.0%) died. The CIR, EFS and OS at 3 years were 12.7%, 77.5% and 82.8%, respectively. The factors including age at diagnosis, sex, initial WBC count, presence of extramedullary leukemia, C-KIT expression, additional chromosomal abnormalities, and CR after the first course of chemotherapy were analyzed by multivariate regression analysis of Cox. Multivariate analysis identified that additional chromosomal abnormalities was the only independent risk factor affecting OS (HR=4.289, 95%CI 1.070-17.183, P=0.040). Conclusions: Pediatric CBF-AML was a unique setting of prognostic subtypes. Chemotherapy produced good responses. Additional chromosomal abnormalities was the only independent risk factor for OS in pediatric CBF-AML.

Curcumin attenuates IR-induced myocardial injury by activating SIRT3.

OBJECTIVE: Ischemia-reperfusion (IR) injury remains an unresolved and complicated situation in clinical practice. In this study, H9c2 cardiomyocytes were subjected to curcumin (Cur) treatment in the absence or presence of the silent information regulator 3 (SIRT3) inhibitor 3-TYP and were then subjected to IR. MATERIALS AND METHODS: H9c2 cells and male Sprague-Dawley (SD) rats were cultured. MTT assay was performed to assess H9c2 cell viability. Cellular apoptosis was analyzed by TUNEL assay. The expressions of Bcl-2, Bax, SIRT3, and AcSOD2 were measured by Western-blotting. The activities of SOD, GSH-Px, and MDA were determined using commercially available kits. The myocardial infarct size was evaluated using TTC staining. RESULTS: Cur significantly increased H9c2 cell viability, decreased the cell apoptotic index, and altered several biochemical parameters, including upregulation of the anti-apoptotic protein Bcl-2, downregulation of the proapoptotic protein Bax and AcSOD2, activation of SIRT3, increase in SOD and GSH-Px activity, and decrease in MDA content. In isolated rat hearts, Cur significantly improved cardiac function, decreased infarct size, and lowered lactate dehydrogenase levels. These protective effects induced by Cur were reversed by treatment with the SIRT3 inhibitor 3-TYP. CONCLUSIONS: These results demonstrate that Cur protects cardiomyocytes and that rat hearts were exposed to IRI by activating SIRT3.

[Prognostic factors of pediatric patients with Ph-positive acute lymphoblastic leukemia].

Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children. Methods: The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model. Results: In the 68 cases, the proportion of male to female was 2.1∶1, with a median age of 8 (1-16) years, and the median overall survival (OS) and disease free survival (DFS) were 16.8 months and 13.5 months, respectively. The early response rate to treatment was 43.9%, with myeloid-antigens-expression group lower than the non-expression group (29.6% vs 61.3%, χ2=5.814, P=0.020); The complete remission (CR) rate after one-course induction therapy was 86.2% (56/65), with good-response group higher than the poor-response group (100.0% vs 74.2%, χ2=6.680, P=0.003);The CR rate after induction in patients receiving imatinib plus chemotherapy was higher than the patients receiving chemotherapy only (94.9% vs 73.1%, χ2=5.185, P=0.024). The 2-and 5-year OS were (61.4±7.0)% and (50.8±8.1)%, respectively. The 2-and 5-year DFS were (54.6±6.8)% and (48.6±7.3)%, respectively. Univariate analysis showed that the initial WBC, LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year OS rate (all P<0.05). LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year DFS rate (all P<0.05). Multivariate prognostic analysis for OS (RR=45.7, 95% CI 1.4-1 528.2, P=0.033) and DFS (RR=52.3, 95% CI 1.6-1 725.9, P=0.026) showed that the spleen ≥ 3 cm was the independent risk factor. Conclusions: Pediatric Ph+ ALL is a special condition with unique clinical and biological features. The early response to treatment was poor in patients with myeloid-antigens-expression, which resulted in a low CR rate after one-course induction and the administration of imatinib can remarkably improve the CR rate. Initial spleen ≥ 3 cm is an independent prognostic factor. The efficacy of chemotherapy alone is poor, and imatinib combined with chemotherapy is applauded in the aim of improving outcomes.

Risk factors for imipenem-resistant Pseudomonas aeruginosa in neonatal intensive care units in south China.

This multi-centre retrospective study was designed to investigate the risk factors for infection with imipenem-resistant Pseudomonas aeruginosa in neonatal intensive care units (NICUs) in south China. All patients with confirmed P. aeruginosa infection from eight NICUs in south China were divided into two groups: imipenem-susceptible P. aeruginosa and imipenem-resistant P. aeruginosa. Data were analysed using Chi-squared test and logistic regression. In total, 188 medical records were reviewed. On multi-variate logistic analysis, the only independent risk factor was imipenem treatment within two weeks of isolation of P. aeruginosa (odds ratio 6.409, 95% confidence interval 1.926-21.333).

[Study on the three-dimensional mapping to reduce the X-ray exposure dose of interventional doctors in radiofrequency catheter ablation of atrioventricular nodal reentry tachycardia].

Objective: To explore the advantage of radiofrequency catheter ablation under the three-dimensional mapping in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT) in reducing the X-ray exposure dose of interventional doctors. Methods: 79 patients with AVNRT, in the first hospital of Shanxi Medical University from January 2015 to June 2016, performed to do radiofrequency catheter ablation treatment were selected, and according to the random number method were divided into two-dimensional mapping group and three-dimensional mapping group. The two-dimensional mapping group was mapped the ablation target at the X-ray, while the ablation target was mapped by CARTO 3 system in the three-dimensional mapping group. Compare the X-ray fluoroscopy time, success rate, complications rate and doctor's X-ray exposure dose between the two groups. Results: Compared with the two-dimensional mapping group, acute success rate and complication rate of the three dimensional mapping group were not statistically significant (P>0.05) , while the X-ray fluoroscopy time and the X-ray dose of the three-dimensional mapping group decreased significantly, the difference was statistically significant (P<0.05) . Conclusion: Three-dimensional mapping can significantly reduce the X-ray irradiation time and interventional doctor's X-ray exposure dose in radiofrequency catheter ablation of AVNRT patients and the potential hazards of ionizing radiation on the human body.

[Preliminavy clinical study of the treatment of hemorrhoids by superselective embolization of superior rectal artery].

Objective: To investigate the safety and feasibility of the treatment of hemorrhoids by superselective arterial embolization. Methods: The clinical data of 15 patients with grade Ⅱ to Ⅳ hemorrhoids were collected who were treated by superselective SRA embolization.According to the number and shape of SRA in the vicinity of the dentate line, chosed coils, PVA particles and gelfoam particles, ethanol and bletilla mixture of gelfoam particles for embolization.And intraoperative operations, postoperative complications, follow-up treatment results were observed. Results: The interventional procedures were successfully accomplished in all 15 cases.The operation time was (30±14) min, and the hospital stay was 1-7 (2.0±1.8) days after operation, and the patients recovered to normal life in 12 hours after the operation.Tenesmus (14/15), pain (5/15) and low fever (11/15) can alleviate without special treatment. All patients were follow up (19.0±2.6) months, bleeding symptoms were cured, there's no serious complications. Conclusion: The treatment of hemorrhoids by transcatheter superselective embolization of superior rectal artery is technically safe and feasible.

[Effects of apigenin on lipopolysaccharide induced proliferation of rat aortic vascular smooth muscle cells].

Objective: To investigate the effect of natural active compounds apigenin (API) on the proliferation of rat aortic vascular smooth muscle cells (VSMCs) induced by lipopolysaccharide (LPS) and related mechanisms. Methods: VSMCs of primary cultured SD rats were obtained and the cytotoxic effects of API (0, 10, 20, 40 and 80 µmol/L) was explored by CCK-8 method. Impact of LPS (0, 0.1, 1, 10 and 100 µg/ml) on VSMCs proliferation and the impact of API (0, 10, 20, 40 µmol/L) on LPS (10 µmol)-induced VSMCs proliferation by CCK-8 methods. Using EdU and FCM method, we observed the effect of API on proliferation of VSMCs induced by LPS. VSMCs proliferation and cell cycle were also assessed by EdU method and FACS in 10 µg/ml LPS, 10 µg/ml LPS+ 40 µmol/L API and equal volume DMSO treated VSMCs. Results: (1) CCK-8 cell vitality test showed that cell vitality was not affected by 0-40 µmol/L API, while cell vitality was significantly reduced by 80 µmol/L API (57%), which was significantly lower than in blank group (P<0.05). (2) VSMCs proliferation was significantly promoted by 0.1, 1 and 10 µg/ml LPS and peaked in 10 µg/ml LPS stimulated VSMCs group, while VSMCs proliferation was significantly reduced in 100 µg/ml LPS stimulated group (P<0.05 vs. blank group). (3) LPS (10 µm/ml) induced VSMCs proliferation was not affected by 10 µmol/L API, which was significantly inhibited by 20 and 40 µmol/L API (both P<0.05 vs. LPS). (4) VSMCs proliferation assessed by EdU was significantly higher in LPS group than in blank group (P<0.01), which could be significantly reduced by cotreatment with API (P<0.01). (5) FACS results showed that percent of VSMCs in G0/G1 stage was significantly lower in LPS group compared to blank group (P<0.05), which could be significantly increased post API treatment (P<0.05 vs. LPS), while percent of VSMCs in S stage was significantly lower post API treatment in comparison with LPS group. Conclusion: API can significantly inhibit LPS-induced proliferation of VSMCs, partly through inhibiting mitosis and inducing G0/G1 cell cycle arrest.

Quercetin upregulates ABCA1 expression through liver X receptor alpha signaling pathway in THP-1 macrophages.

OBJECTIVE: Quercetin has been reported to have the activities of antioxidant, anti-inflammatory, anti-virus, anti-cancer and so on. Many studies showed that quercetin could lower blood pressure and improve blood capillary elasticity, and it can also reduce LDL oxidation and prevent atherosclerosis. Although quercetin has been recognized to have the function of preventing atherosclerosis, little is known about its underlying mechanism. In this study, we try to explore whether quercetin up-regulates LXRa-mediated ABCA1 expression. MATERIALS AND METHODS: THP-1 cells were cultured. The expression of ABCA1 and LXRa were detected by real-time PCR and western blot. Cellular cholesterol efflux from THP-1 macrophages was analyzed using liquid scintillation counting assays. RESULTS: Real-time PCR and Western blot showed quercetin increased the expression of ABCA1 and LXRα at both the mRNA and protein levels in a concentration-dependent and time-dependent manner in THP-1 macrophages. Liquid scintillation counting assays indicated quercetin increased the cholesterol efflux and decreased the cellular cholesterol content. Furthermore, the expression of LXRa was decreased after THP-1 macrophage transfected with LXRα siRNA. Meanwhile, the expression of ABCA1 was also recovered after incubated with the combination of LXRa siRNA and quercetin compared with quercetin alone. CONCLUSIONS: Quercetin could increase ABCA1 expression and cholesterol efflux through LXRα pathway to eventually promote RCT in the THP-1 macrophage.

[The protective effect of alpha-2 adrenergic agonist on cranial nerve in rats with brain injury].

OBJECTIVE: To investigate the neuroprotective effect of α2 adrenergic agonist, dexmedetomidine on tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) in brain tissue and serum S-100ß protein level in traumatic brain injury rats. METHODS: Seventy-two male Sprague-Dawley rats were randomly divided into sham operation group (group S), traumatic brain injury group (group C), and dexmedetomidine group (group D), 24 rats in each group; each of which was divided into 6, 12, 24 and 48 hours subgroup, 6 rats in each subgroup. Parietal brain contusion was produced by reformed Feeney method. The group S underwent sham operation without blunt force stroke; group D underwent blunt force stroke, then received loading dose of dexmedetomidine, 3 µg/kg with common jugular vein injection and continued infusion with 3 µg·kg(-1)·h(-1) for 2 hours. The total dosage of dexmedetomidine was 9 µg/kg with a volume of 4 ml; group C underwent 0.9% NaCl, 4 ml injection at the same time point with the same method. The S-100 protein activity in arteria cruralis serum was detected at the each time point by ELISA and TNF-α, IL-6 in the brain tissue were detected by ELISA. RESULTS: There were no significant difference of TNF-α activity among time point of 6, 12, 24 and 48 h in group S ((2.07±0.06), (2.01±0.03), (2.11±0.05), and (2.08±0.04) pg/mg, F=1.147, P>0.05), no significant difference of IL-6 activity among the same time point ((4.03±0.06), (4.07±0.09), (4.06±0.04), and (4.55±0.09) pg/mg, F=1.176, P>0.05), and no significant difference of serum S-100ß activity among the same time too ((0.37±0.07), (0.36±0.02), (0.35±0.06), and (0.39±0.11) µg/L, F=1.045, P>0.05). The above indexes in group C were higher than those in group S, and the above indexes in group D were higher than those in group S and lower than those in group C (all P<0.05). CONCLUSION: Alpha-2 adrenergic agonist, dexmedetomidine could dramatically inhibit inflammatory reaction induced by traumatic brain injury in rats and protect brain tissue.

Quercetin inhibits angiotensin II induced apoptosis via mitochondrial pathway in human umbilical vein endothelial cells.

OBJECTIVE: Quercetin exhibits various biological functions including anti-oxidation, anti-inflammatory, antiviral, immunity and anticancer, etc. It can also lower blood pressure and improve blood capillary elasticity. Angiotensin II (Ang II) has been showed to induce apoptosis of human umbilical vein endothelial cells. In this study, we attempted to clarify the effect of quercetin on Ang II induced apoptosis. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured. The cytotoxicity was determined by MTT assay. HUVECs apoptosis was determined by DAPI staining and flow cytometry. The mitochondrial transmembrane potential was observed by JC-1 staining. The expression of cytochrome c, Bcl-2, Bax, activated-caspase-3 and activated-caspase-9 was measured by Western blot. RESULTS: MTT assays showed Ang II decreased cell viability in a concentration-dependent manner in HUVECs. Notably, quercetin presented very little effect on HUVECs. Quercetin inhibited the effect of Ang II on HUVECs in a concentration- and time-dependent manner. Furthermore, the loss of mitochondrial membrane potential, upregulation of cytochrome c and Bax, downregulation of Bcl-2, and activation of caspase-9 and caspase-3 caused by angiotensin II were also recovered after treated with quercetin. CONCLUSIONS: Quercetin could inhibit Ang II induced apoptosis of human umbilical vein endothelial cells via the mitochondrial pathway.

Effect of continuous infusion of midazolam on immune function in pediatric patients after surgery.

The current study was performed to investigate the effects of midazolam on immune function in pediatric patients after surgery and possible mechanism involved. Patients who needed sedation for more than 2 consecutive days after undergoing surgery in the Pediatric Surgery Department of our hospital were enrolled for the study. Fifty-six patients (5-14 years old) were randomly divided into midazolam and propofol treatment groups (N = 28 each in each group). Pediatric patients received midazolam or profolol via continuous intravenous administration, and their plasma cytokine levels were compared after 48 h. Cultured rat C6 brain glioma cells were pretreated with a range of concentrations of midazolam or propofol for 60 minutes prior to incubation with 10 ng/mL IL-1ß in serum-free medium or vehicle for 36 h. IL-6 concentration was subsequently measured using ELISA. In comparison with levels measured before the infusion of midazolam for 48 h, concentrations of all cytokines decreased, with the differences in IL-1ß, IL-8, and TNF-α concentrations reaching significance (all P < 0.05). Midazolam significantly suppressed the IL-1ß-induced release of IL-6 in rat C6 glioma cells. This inhibition was concentration-dependent between 0.3 and 3 µM, with 3 µM concentration of midazolam decreasing the IL-1ß-induced release of IL-6 by 43.58%. Midazolam can significantly inhibit the release of cytokines in pediatric patients after surgery. One of the mechanisms may be the inhibition of IL-1ß- induced release of IL-6 in the central nervous system.

Anisotropic quantum transport in a network of vertically aligned graphene sheets.

Novel anisotropic quantum transport was observed in a network of vertically aligned graphene sheets (VAGSs), which can be regarded as composed of plenty of quasi-parallel, nearly intrinsic, freestanding monolayers of graphene. When a magnetic field was perpendicular to most graphene sheets, magnetoresistance (MR) curves showed a weak localization (WL) effect at low field and a maximum value at a critical field ascribed to diffusive boundary scattering. While the magnetic field was parallel to the graphene sheets, the MR maximum disappeared and exhibited a transition from WL to weak antilocalization (WAL) with increasing temperature and magnetic field. Edges as atomically sharp defects are the main elastic and inelastic intervalley scattering sources, and inelastic scattering is ascribed to electron-electron intervalley scattering in the ballistic regime. This is the first time simultaneously observing WL, WAL and diffusive boundary scattering in such a macroscopic three-dimensional graphene system. These indicate the VAGS network is a robust platform for the study of the intrinsic physical properties of graphene.