Objective To observe-the different effects of 2 doses recombinant human granulocyte colony-stimulating factors (rhG-CSF) on Nogo receptor(NgR) expression in the brain tissue of neonatal rats after hypoxic-ischemic brain damage(HIBD) at different times in order to reveal the neuroprotective effects of rhG-CSF.Methods Seven-day neonatal Sprague-Dawley(SD) rats were randomly divided into 4 groups by drawing method:sham operation group,model group,low-dose rhG-CSF group and high-dose rhG-CSF group,24 rats in each group.Then each group was divided into 4 subgroups (6 rats in each subgroup)and all rats were exterminated at different times after HIBD(1 d,3 d,7 d and 14 d).In the low-dose rhG-CSF group and high-dose rhG-CSF group,the rats were given daily doses of rhG-CSF 50 μg/kg,100 μg/kg respectively for 7 days by subcutaneous injection immediately after the molding(total 7 injections).In model group,rats received an injection of same amount of 9 g/L saline.In sham operation group,rats received no special treatment.Brain tissues of rats from each group were collected at different time points.The expressions of NgR protein and NgR mRNA in the left brain tissue were detected by immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction (PCR).Results Immunohistochemistry:NgR proteins were constitutively expressed in the cerebral cortex in sham operation group at each time point;compared with sham operation group,the expressions of NgR in model group were increased markedly at each time point (135.67 ± 16.63,173.98 ± 17.82,234.00 ± 14.70,319.59 ± 25.22),and the differences were statistically significant(all P ＜ 0.01);compared with model group,the expressions of NgR in the cerebral cortex in low-dose rhG-CSF group (134.35 ± 8.89,109.04 ± 12.62,75.99 ± 13.39) and high-dose rhG-CSF group (81.38 ± 12.25,80.14 ± 10.50,72.58 ± 13.66) on the 3rd,7th,14th day were reduced significantly (all P ＜ 0.01).Compared with low-dose rhG-CSF group,the protein expressions of NgR in the high-does rhG-CSF group were decreased faster,and had the marked difference on the 3rd,7th day (P ＜ 0.05).Real-time fluorescent quantitative PCR:compared with the sham operation group,the expressions of NgR mRNA increased gradually in the cerebral cortex in the model group (1.34 ± 0.24,1.88 ± 0.27,2.88 ± 0.84,4.26 ± 0.86),the differences in NgR mRNA expression were statistically significant at different times(all P ＜ 0.05) ; compared with model group,the expressions of NgR mRNA in low-dose rhG-CSF group on the 7th (1.08 ± 0.30),14th day (0.93 ± O.26) and high-dose rhG-CSF group on the 3rd (0.61 ± 0.10),7th (0.56 ± 0.28),14th day (0.47 ± 0.12) were significantly different (all P ＜ 0.05).The expressions of low-dose group and high-dose group were reduced gradually.The NgR mRNA expression reduced more quickly in the high-dose group than in the low-dose rhG-CSF group and had substantial difference between two groups in 3 days (P ＜ 0.05).Conclusions The findings suggest that rhG-CSF intervention can reduce the expressions of NgR in the brain tissues of neonatal rats after HIBD,and low-dose rhG-CSF also has neuroprotective effect,but it could be weaker than high-dose rhG-CSF.

Objective:To study the correlation among lipoprotein (a) [Lp (a)] ,its gene polymorphism and degenera‐tive calcific aortic valve disease (DCAVD) .Methods :From Feb 2010 to Jan 2014 ,a total of 164 DCAVD cases trea‐ted in our hospital were enrolled as DCAVD group ,another 164 healthy subjects undergoing physical examination in the same period were selected as normal control group .Relationship among Lp (a) level ,its gene polymorphism and aortic valvular calcification was compared and analyzed ,and Logistic regression analysis was used to analyze in‐dependent risk factors of DCAVD . Results :Lp (a ) gene possesses four point mutations in population , namely rs10455872 ,rs6415084 ,rs3798221 and rs7770628. In DCAVD group ,Lp (a) level of AG genotype was significantly higher than that of AA genotype [ (325.5 ± 108.2) mg/L vs .(211.7 ± 135.4) mg/L] in rs10455872 gene pheno‐type ,Lp (a) level of CC+TT genotype was significantly higher than that of CT genotype [ (287.9 ± 144.1) mg/L vs .(240.7 ± 127.2) mg/L] in rs6415084 gene phenotype ,and Lp (a) level of TT+ CC genotype was significantly higher than that of CT genotype [(304.1 ± 124.1) mg/L vs .(226.8 ± 101.6) mg/L] in rs7770628 gene phenotype , P<0.05 or <0.01 ;patient′s percentage of valvular calcification of AG genotype was significantly higher than that of AA genotype (90.0% vs .61.7% ) in rs10455872 , patients percentage of valvular calcification of CC +TT geno‐type was significantly higher than that of CT genotype (83.8% vs .66.7% ) in rs6415084 ,and patient′s percentage of valvular calcification of TT+CC genotype was significantly higher than that of CT genotype (87.3% vs .63.4% ) in rs7770628 , P<0.05 or <0.01. Logistic regression analysis indicated that rs10455872 ,rs6415084 ,rs7770628 and Lp (a) level were independent risk factors for valvular calcification of DCAVD (OR=1.67~2.31 , P<0.01 all) . Conclusion :Lp (a) gene polymorphism (rs10455872 ,rs6415084 and rs7770628) and plasma Lp (a) level are signifi‐cantly correlated to valvular calcification of DCAVD ,which may be susceptible genes for DCAVD occurrence .

BACKGROUND: Mesenchymal stem cells attract extensive attention because of good biological characteristics and broad prospects, but the cells gradually show the characteristics of the aging with the increase of individual age or incubation time in vitro. Nonhuman primates have similar biological characteristics with human being, and have unique advantage in the animal model and disease treatment research.OBJECTIVE: To analyze the difference in proliferation and differentiation of bone marrow mesenchymal stem cells from macaques at different ages and to explore the effect of age on bone marrow mesenchymal stem cells and the possible mechanism.METHODS: Bone marrow samples from male macaques aged < 3 years and over 20 years were collected through bone marrow puncture, and divided into young group and elder group, with three macaques in each group. Then, bone marrow mesenchymal stem cells were isolated and cultured in vitro, and the morphological changes, proliferation and differentiation ability were observed. Age-related beta-galactosidase staining was performed, and protein microarray and ELISA were used to detect cytokine levels.RESULTS AND CONCLUSION: With age, the proliferation and differentiation of bone marrow mesenchymal stem cells from the elder macaques were reduced significantly, and the number of senescent cells increased significantly; the levels of interleukin-1b, interleukin-4, interleukin-6, tumor necrosis factor α and vascular endothelial growth factor were elevated obviously, the levels of heparin-binding basic fibroblast growth factor and placental growth factor were reduced. These findings indicate that the body's aging lead to the reduction in the proliferation, differentiation and cytokine secretion of bone marrow mesenchymal stem cells.

Objectives To investigate the correlation between dietary fatty acids intake of pregnant women and neonatal anthropometry at birth. Methods Women in early pregnancy were recruited with appropriate value of weight gain in pregnancy. Instant photography was used to assess the dietary situation in both the second trimester and the third trimester to calculate the intakes of food, energy, macronutrients, and fatty acids. The body weight, height and BMI at birth were evaluated with Z scores. The correlation between dietary fatty acids of pregnant women and neonatal anthropometry at birth were analyzed. Results There were 516 pregnant women recruited in this study. The average intakes of polyunsaturated fatty acids (PUFA) and the proportion of total fatty acids in the two trimesters were 15 . 09 g/d, 23 . 93% and 17 . 18 g/d, 24 . 86%. In the second trimester the intakes of n-6 and n-3 PUFA were 14 . 23 g/d and 3 . 45 g/d, and in the third trimester, n-6 and n-3 PUFA were 16 . 08 g/d and 3 . 81 g/d, the average intakes in the third trimester were signiifcantly higher than those in the second trimester (P??0 . 05 ). The intake of DHA ( 64 . 43 mg/d) in the second trimester was lower than that in the third trimester 75 . 12 mg/d, (P??0 . 05 ).The dietary intakes of n-3 PUFA, n-6 PUFA and n-6/n-3 ratio in the second trimester were positively correlated with neonatal BMI r=0 . 142~0 . 189 , P??0 . 05 ). Conclusions The dietary ratio of n-6/n-3 PUFA in the second trimester was positively correlated with neonatal BMI, suggesting that moderately increasing the intake of n-3 PUFA may play a positive role in reducing childhood obesity.

Objective To study the clinical effects of continuous blood purification (CBP) in the treatment of newborns with severe sepsis and multiple organ dysfunction syndrome (MODS). Method From May 2013 to November 2018, the clinical data of infants with severe sepsis and MODS receiving CBP in the neonatal department of our hospital were retrospectively analysed. Changes of blood pressure, arterial partial pressure of oxygen/inhaled oxygen concentration (PaO2/FiO2), pH, serum potassium, sodium, urea nitrogen, creatinine, urine volume and maintenance dose of adrenaline at different time points before and after CBP were analysed. Result According to the inclusion and exclusion criteria, a total of 8 newborns with sepsis and MODS were enrolled in the study. One patient had the complication of perforated colon, and the other one had acute renal failure. The number of affected organs in these infants was 3～5. Six cases began CBP treatment within 1～5 days after admission, and the other two cases began CBP treatment on the 38th and 47th days after admission. The average treatment duration was (58.6±25.9) h. The effective rate of CBP in the treatment of severe sepsis with MODS was 75.0％(6/8). Blood pressure was increased at 6 h, 12 h, 24 h and 48 h after treatment and at the end of treatment. PaO2/FiO2 and blood pH were increased. The urine volume was increased at 24 h and 48 h after treatment and at the end of treatment (P<0.05). Serum potassium, urea nitrogen and creatinine were significantly decreased (P<0.05). The maintenance dose of adrenaline was also decreased significantly at 12 h after CBP (P<0.05), and withdrawn at 48 h after treatment. Only one case experienced membrane blockage during CBP. Dialysis was continued after the replacement of filtration membrane. No other complications existed. Conclusion CBP is effective in the treatment of neonatal severe sepsis with MODS. It can improve the circulation and renal function.

Objective To explore the risk factors of the occurence and 28-day death of acute respiratory distress syndrome (ARDS) in intensive care unit (ICU). Methods A prospective multicentral cohort study was conducted. The patients from five ICUs of grade A tertiary hospitals in Beijing from July 2009 to March 2014, including sepsis,septic shock,trauma,pneumonia,aspiration,massive blood transfusion,bacteremia and pulmonary contusion,were enrolled. Researchers in each center reported the records with uniform tables,which included demographic,systemic conditions,the primary disease,and the severity within 24 hours,past history and so on. According to the admission diagnosis in ICU,these patients were divided into ARDS group and other severe disease control group. The risk factors of occurence and prognosis of ARDS were analyzed by univariate analysis,multivariate logistic regression and multivariate COX regression analysis. Kaplan-Meier method was applied to draw the 28-day survival curves of the two groups. Results There were 343 critical patients included in this prospective multicenter cohort study,of which 163 patients who developed ARDS were considered as ARDS group(2 case lost to follow-up, and 49 died)and 180 patients who did not developed ARDS regarded as severe control group(1 case lost to follow-up, and 34 died). The 28-day mortality of ARDS group was significantly higher than that of severe control group〔30.43%(49/161)vs. 18.99%(34/179),χ2=6.013,P=0.014〕. Multivariate logistic analysis showed that aspiration〔odds ratio(OR)=6.390,95% confidence interval(95%CI)=2.046-19.953,P=0.001〕,history of alcohol (OR=4.854,95%CI=1.730-13.617,P=0.003),sepsis(OR=2.859,95%CI=1.507-5.425,P=0.001), pneumonia(OR=2.822,95%CI=1.640-4.855,P<0.001),acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score(OR=1.050,95%CI=1.007-1.094,P=0.022)were significantly associated with increased risk of ARDS occurence. When respiratory rate>30 beats/min(OR=3.305,95%CI=1.910-5.721,P<0.001), heart rate>100 beats/min(OR=2.101,95%CI=1.048-4.213,P=0.037)happened in critically ill patients, it highly suggested ARDS would happen. The proportion of the patients whose serum creatinine>176.8 μmol/L in ARDS group was lower than that in control group(OR=0.387,95%CI=0.205-0.733,P=0.004). Multivariate COX regression analysis showed that old age and septic shock were significantly associated with the increased risk of in 28-day death of ARDS〔advanced age:hazard ratio(HR)=1.040,95%CI=1.018-1.064,P<0.001;septic shock:HR=3.209,95%CI=1.676-6.146,P<0.001〕. Kaplan-Meier showed that the survival patients in ARDS group was significantly lower than those in severe control group(χ2=7.032,P=0.008). Conclusions Among critical ill patients,aspiration,history of alcohol,sepsis,pneumonia,increased APACHEⅡ score were the risk factors of ARDS development. Respiratory rate>30 beats/min and heart rate>100 beats/min could predict the occurrence of ARDS in critical patients. Old age and septic shock were the risk factors of 28-day death of ARDS.

Objective To evaluate the differences of toxicities,therapeutic efficacy and immune function between induction chemotherapy followed by sinusoidal chrono-modulated infusion and flat intermittent infusion of cisplatin (DDP)with intensity-modulated radiotherapy (IMRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Methods Seventy patients with biopsydiagnosed stages Ⅲ and Ⅳ B NPC (according to the 2010 UICC staging system) were treated with two-cycle induction chemotherapy before chemoradiotherapy in Guizhou Cancer Hospital.The TPF chemotherapy regimen was administered as follows:The TXT and DDP with the dose of 75 mg/m2 was carried out by bolus infusing for the first day,the 5-FU with 750 mg · m-2 · d-1 was carried out by continuous intravenous pumping for the first day to fifth day(120 h).The induction chemotherapy was 21 days per cycle,for two cycles.After that all patients were randomly treated with 2-3 cycles of sinusoidal chronomodulated infusion or flat intermittent constant rate infusion of DDP with IMRT.Using a multi-channel programmed pump,the patients were given 12 h continuous infusions of DDP (100 mg/m2) for day one,repeated every 3 weeks for 2-3 cycles.DDP was administered from 10:00 am to 10:00 pm.Concurrent radiotherapy regimen was administered as follows:GTVnx 69.96-73.92 Gy/33 f,PTVnx 69.96 Gy/33 f,PTVnd 69.96 Gy/33 f,PTV1 60.06 Gy/33 f,PTV2 50.96 Gy/28 f.Results The main toxicities of chemoradiotherapy in the group of sinusoidal chrono-modulated infusion were bone marrow suppression:leukocytes,and then nausea,oral mucositis and hemoglobin.The main toxicities of chemoradiotherapy in the group of flat intermittent constant rate infusion were bone marrow suppression:hemoglobin,leukocytes,and then nausea,oral mucositis.No significant differences were observed for toxicities(P ＞ 0.05).After concurrent chemoradiotherapy,the complete response rate (CR),partial response rate (PR),stable disease rate(SD),progressive disease rate (PD) and overall response rate (ORR) were 11.4％,85.7％,2.9％,0 and 97.1％ in the group of sinusoidal chrono-modulated infusion.The CR,PR,SD,PD,ORR in the group of flat intermittent constant rate infusion were 22.9％,74.2％,2.9％,0,97.1％,respectively.However,there was no significant differences of effect in the two Arms (P ＞ 0.05).For sinusoidal ehrono-modulated infusion and flat intermittent infusion group,the 2-year overall survival(OS) were 82.9％ and 94.3％ respectively,the 2-year progression-free survival(PFS) were 77.1％,91.4％ respectively,and the 2-year distant metastasis free survival (DMFS) were 82.9％,91.4％ respectively.The value of CD3 + in the group of sinusoidal chrono-modulated infusion was higher than the group of flat intermittent constant rate infusion after therapy (Z =3.254,P ＜ 0.05).The value of CD4 +,CD8 +,CD16 + CD56 +,CD19 +,and CD4 +/CD8 + had no differences in two Arms (P ＞ 0.05).Conclusions No significance differences on the toxicities,therapeutic efficacy and survival were observed between the two groups,but immune function might be improved in the sinusoidal chrono-modulated infusion group.

Objective: To explore the prognostic relationship between initial absolute lymphocyte count(ALC) of peripheral blood and primary immune thrombocytopenia (ITP) in children, in order to provide basis for judging the prognosis and treatment of ITP in children. Methods: Clinical data of 166 children with primary ITP in children admi-tted at the Affiliated Hospital of Guizhou Medical University from January 2014 to March 2018 were analyzed retrospectively, and they were followed up by clinic and telephone, the prognostic factors (gender, age, ethnicity, inducement, bleeding, initial ALC, platelet count and treatment) were statistically analyzed, and the relationship between ALC of peripheral blood and the prognosis of children with ITP was observed. Results: Of 166 children with ITP, 89 cases (53.6%) had remission within 3 months, 18 cases (10.8%) within 3-12 months, 20 cases (12.0%) within 1-4 years, a total of 39 cases (23.5%) were refractory (no remission in 1-10 years), the remission rate within 1 year was 64.5%, the total remission rate was 76.4%.ALC of remission cases was (4.58±2.87)×10⁹/L within 3 months, (4.47±2.04)×10⁹/L within 3-12 months, and (2.86±1.61)×10⁹/L within 1- 4 years.Thirty-nine cases (23.5%) were refractory(no remission in 1-10 years), ALC of them was (2.07±0.98)×10⁹/L, and there were significant differences among different groups (F= 12.06, P<0.01). Univariate analysis showed that age (F=27.28), pre-morbidity history of infection and vaccination history(χ²= 9.31), initial ALC (F=12.06) at initial diagnosis were related with the prognosis of children with ITP (all P<0.05). Multivariate analysis showed that the history of infection before onset, the history of vaccination(95%CI: 0.19 to 1.51, P<0.05)and initial ALC(95%CI: -0.64 to -0.23, P<0.001) at the time of initial diagnosis were independent factors affecting the prognosis of children with ITP.The receivers operating characteristic (ROC) was drawn with the development of chronic disease (course >12 months) as state variable and ALC as test variable.The area under curve(AUC) was 0.765(P<0.05), cut-off point was 3.925×10⁹/L, sensitivity was 0.542, and specificity was 0.966. Conclusions Initial ALC can be used as one of the prognosis index of ITP in children, and low ALC is the risk signal for chronic development of ITP in children.

Objective To investigate the impact of clinical factors on survival in patients receiving concurrent chemotherapy and three?dimensional radiotherapy ( 3DRT) for stage IV non?small cell lung cancer ( NSCLC) . Methods A total of 203 patients were enrolled in a prospective clincial study from 2008 to 2012, and among these patients, 178 patients were eligible for analysis of clinical factors. All patients were treated with platinum?based doublets chemotherapy, with a median number of chemotherapy cycles of 4( 2?6 cycles) and a median dose of 3DRT of 60?3 Gy (36?0?76?5 Gy).The Kaplan?Meier method was used to calculate overall survival ( OS) rates, the log?rank test was used to compare survival rates between groups, and the Cox regression model were used for multivariate analysis. Results The 1?, 2?, and 3?year overall survival rates were 56%, 16%, and 10%, respectively, and the median survival time was 13 months (95% CI=11?500?14?500). The univariate analysis showed that platelet count ≤221×109/L, neutrophil count ≤5.2×109/L, white blood cell count<7×109/L, and improvement in Karnofsky Performance Scale ( KPS) after treatment significantly prolonged OS ( P=0?000,0?022,0?003, and 0?029) , and metastasis to a single organ and hemoglobin≥120 g/L tended to prolong OS (P=0?058 and 0?075). The multivariate analysis showed that white blood cell count<7×109/L, platelet count ≤221×109/L, and improvement in KPS after treatment were beneficial to OS ( all P<0?05) . Conclusions White blood cell count and platelet count before treatment and KPS after treatment are prognostic factors for patients with stage IV NSCLC receiving concurrent chemotherapy and 3DRT. Clinical Trial Registry ClinicalTrials. gov, registration number:ChiCTRTNC10001026.

Objective To investigate the efficacy,adverse reactions and immune function of time-adjusted chemotherapy combined with intensity-modulated radiation therapy (IMRT) and conventional chemotherapy combined with IMRT for locally advanced nasopharyngeal carcinoma.Methods Random number grouping method was used to divide 66 cases of locally advanced nasopharyngeal carcinoma into 2 groups,of which 36 cases in the time-adjusted chemotherapy group and 30 cases in the conventional group.Both of them received docetaxel + cisplatin + fluorouracil regimen to induce chemotherapy for 2 cycles.The time-adjusted chemotherapy group was treated with intravenous injection of electronic automatic injection pump,the conventional group was treated with conventional intravenous infusion,and both groups were treated with synchronous cisplatin combined with IMRT.Calculated survival rate was generated by Kaplan-Meier method and long-term adverse reactions was evaluated according to CTC 3.0 criteria.Results The 3-year overall survival (OS) rate was 86.1％ and 93.3％ in the time-adjusted chemotherapy group and the regular group,the 3-year progress-free survival (PFS) was 83.3％ and 93.3％,the 3-year RFS was 88.5％ and 93.3％,and the 3-year recurrence-free survival was 94.1％ and 100％ respectively with no statistically significant difference (P ＞ 0.05).The dryness and hearing loss of the time-adjusted chemotherapy group had a decreasing trend compared with the conventional group.However,CD3 +,CD3 + CD4 +,CD3 + CD4 + CD8 +,and CD4 +/CD8 + of the time-adjusted chemotherapy group had an increasing trend compared with the conventional group.Conclusions Both time-adjusted chemotherapy and conventional chemotherapy combined with IMRT had comparable mid-term efficacy,but the former had lower adverse reactions,improved quality of life and immune function.Trial registration Chinese clinical trial registry,ChiCTR1800016809