Objective To discuss the maximum tolerated dose of oxaliplatin based on 5-fluorouracil derivative in patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy.Methods From Mar 2015 to Oct 2015,15 locally advanced rectal cancer patients (T3,T4/N +) who received intensity modulated radiotherapy and concurrent chemotherapy with capecitabine and oxaliplatin were enrolled in this study.The prescription dose was 50.6 Gy for gross tumor volume(GTV) and 41.8 Gy for clinical tumor volume(CTV) in 22 fractions within 30 d with concomitant boost.There were four dose-level groups of oxaliplatin as 100,110,120 and 130 mg/m2 tri-weekly and fixed capecitabine dose (825 mg/m2 bid d1-5 per week).The first 12 patients were randomly assigned into 4 groups.For the 130 mg/m3 group,another 3 patients were enrolled because of dose-limiting toxicity (DLT).Treatment related toxicities and response rates were evaluated.Results The most common adverse events(AE) were radiation enteritis,skin reactions,nausea,fatigue,urinary system AE and bone marrow suppression.There was a trend of increase by the dose level of oxaliplatin for toxicities.Groups 100,110 and 120 mg/m2 had none DLT,while group 130 mg/m2 had 1 patient for grade 3 thrombopenia and 1 patient for grade 3 nausea.Postoperative pathology showed that all patients achieved tumor downstaging,among which 0,1,2,3 cases achieved complete remission of the four groups,respectively.Conclusions The combination regimen of capecitabine and oxaliplatin is safe and effective according to the preliminary results.The maximum tolerated dose of oxaliplatin was 130 mg/m2 tri-weekly.

Objective:AFM1-BSA and AFM1-OVA were synthesized and then identified in this experiment.Methods: Using oximation method ,AFM1 was transformed to oxime compounds while the reaction process was monitored via TLC method aiming to identify the compounds.Coupled with carrier protein BSA and OVA respectively , we obtained AFM1-BSA and AFM1-OVA, then identified synthetic antigen via UV spectrophotometry and SDS-PAGE.Antigens were injected into experimental animals , finally obtaining the murine multi-antiserum.Eventually , the multi-antiserums were detected via indirect inhibition ELISA method to judge whether the antigens were effectively or not.Results:After oximation reaction ,the migration distance of oxime compounds in the thin layer plate was shorter.The maximum absorption peak of AFM1-BSA occurred in 274 nm,and was inconsistent with both UV absorption peaks of BSA and AFM 1.The electrophoretic velocity of AFM 1-BSA was less than that of BSA.All the titers of three immunized mice were 1×10-4 approximately;the multi-antiserum from No.3 sample had the best sensitivity ,its IC50 was 359.9 ng/ml.Conclusion:In this study,we obtained AFM1 artificial antigen and murine multi-antiserum of high sensitivity.

Objective:To investigate the correlation between serum cystatin C (CysC) and clinical and pathological features of IgA nephropathy.Methods:Four hundred and twenty-one cases of primary IgA nephropathy diagnosed by renal biopsy in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2010 to January 2021 were retrospectively analyzed. According to the serum CysC level at the time of renal biopsy, the patients were divided into high serum CysC group and normal serum CysC group, and the clinical data and pathological indices of the patients were compared. Spearman correlation analysis was used to analyze the correlation between estimated glomerular filtration rate (eGFR) and serum CysC. The clinicopathological factors related to the serum CysC level were analyzed by multiple linear regression. The area under the receiver operator characteristic curve (AUC) was used to evaluate the ability of serum CysC level to predict related pathological injury.Results:The age, prevalence of hypertension, serum creatinine, urea and uric acid levels of high serum CysC group were significantly higher than those of normal serum CysC group, while the eGFR level was significantly lower than that of normal serum CysC group ( P<0.05). Spearman correlation analysis showed that serum CysC was negatively correlated with eGFR ( r=-0.744, P<0.001). In terms of pathological injury, the degree of renal tubular atrophy and renal interstitial fibrosis (T) and renal arteriole wall thickening (A) in high serum CysC group were more serious than those in normal serum CysC group ( P<0.05). Multiple linear regression analysis showed that the prevalence of hypertension, serum creatinine, urea, uric acid, T and A were correlated with serum CysC levels (standard regression coefficient β=0.048, 0.299, 0.260, 0.134, 0.195, 0.068, respectively, P<0.05). After adding serum CysC on the basis of clinical features, the prediction efficiency of renal tubular atrophy and renal interstitial fibrosis was higher (AUC were 0.829 [95% CI 0.787-0.870], 0.847 [95% CI 0.808-0.886], P<0.05). Conclusions:Patients with older age, hypertension, poor renal function and severe pathological damage are more likely to have elevated serum CysC levels. Serum CysC was related to the prevalence of hypertension, creatinine, urea, uric acid, T and A. Combined with serum CysC level can effectively improve the ability prediction of T.

Objective To understand the prevalence of autism spectrum disorders (ASD) in children aged 0-6 years old and influencing factors in Hainan province.Methods A total of 37 862 children aged 0-6 years were selected from 18 counties in Hainan province for a screening by using questionnaire of "warning signs in child development",then field diagnosis was made,and general descriptive statistic analysis was conducted.The prevalence of ASD and related factors were analyzed with x2 test and unconditional logistic regression model.Results Among 37 862 children aged 0-6 years,235 were diagnosed with ASD,the prevalence of ASD was 0.62％ (0.99％ in boys,0.17％ in girls),the differences was significant (x2=101.91,P=0.000).The prevalence of ASD increased with age (x2=288.62,P=0.000).The prevalence of ASD was significantly higher in urban area than in other areas (x2=114.77,P=0.000).Factors such as full term pregnancy or not,neonatal asphyxia,father' s characteristics,father' s habit of chewing areca or smoking,mother' s general mood,and mother' s induced abortion history were the influencing factors for ASD.Conclusion The prevalence of ASD in children aged 0-6 years was high in Hainan and was influenced by genetic factors,pregnancy and delivery process,parents unhealthy habit before and during pregnancy and other factors.

OBJECTIVETo estimate the significance of the adjustment of acute lymphoblastic leukemia (ALL) risk group by monitoring minimal residual disease(MRD).

METHODTotally 285 children ALL patients who were diagnosed and systematically treated according to CCLG-2008 in Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, from April 2008 to August 2011 were prospectively selected. Among these cases, 62.8% (n = 179) were boys and 37.2% (n = 106) were girls and the median age was 5.3(0.5-14.0). The patients who were at high-risk group initially were excluded. The grouping of cases: the patients were divided into two groups according to the dates of initial diagnosis. Group I had 126 patients who were initially diagnosed between April 2008 and December 2009 in whom therapeutic regimen was not adjusted by reassignment of risk group by MRD. Group II had 159 patients who were initially diagnosed between January 2010 and August 2011 whose therapeutic regimen was adjusted by reassignment of risk group by MRD at specific time (33rd day of induction chemotherapy and 12 weeks after the beginning of chemotherapy). MP-FCM Coulter FC-500 was used in the detection of MRD.

RESULTAmong these 285 patients, 94.0% (n = 268) were diagnosed as B-lineage acute lymphoblastic leukemia and 6.0% (n = 17) were T-lineage acute lymphoblastic leukemia. In group I, 61.9% (n = 78) patients belonged to low-risk group, 38.1% (n = 48) median-risk; in group II, before the adjustment, the rates of the low-risk group and median-risk group were 68.6% (n = 109) and 31.4% (n = 50) , respectively, while after the adjustment they were altered to 53.5% (n = 85) and 39.6% (n = 63) , furthermore 6.9% (n = 11) patients went into the high-risk group. Both groups were followed up for 2.5 years after their diagnoses, the disease of 7.4% (n = 21) patients relapsed, and the rates of two groups were 12.7% (n = 16) and 3.1% (n = 5) respectively, P = 0.009. The rate of serious infection (such as sepsis, pulmonary infection) of all these patients was 32.3% (92/285) , there was no significant difference between the two groups [28.6% (36/126) vs.35.2% (56/159) , P = 0.392]. The mortality of all these patients was 6.7% (19/285) , and that of group I was higher than that of group II [10.3% (13/126) vs. 3.8% (6/159) , P = 0.044]. The 2.5 years overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) of group I were all lower than those of group II in Kaplan-Meier survivorship analysis (all P < 0.05). The two groups were followed up for 2.5 years after their diagnoses, after elimination of the confounding influence of sex, age, FAB subtype, WBC count, ratio of blast cells in bone marrow at diagnosed, chromosome karyotype and fusion gene, reassignment of risk group by MRD was used to calculate the OS, EFS and DFS of ALL patients (all P < 0.05). After the adjustment the risk group was more significant in the assessment of prognosis.

CONCLUSIONThe reassignment of risk group in low and median risk groups children with acute lymphoblastic leukemia by MRD did not increase the rate of serious infection but could reduce the relapse rate and mortality, and was beneficial to increase the patients' OS, EFS and DFS.

Adolescent ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bone Marrow ; pathology ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Flow Cytometry ; Humans ; Infant ; Male ; Neoplasm, Residual ; diagnosis ; drug therapy ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; pathology ; Prognosis ; Prospective Studies ; Recurrence ; Remission Induction ; Survival Rate ; Treatment Outcome

Objective To investigate the effects and possible mechanisms of the growth differentia-tion factor 15(GDF-15)/glial-derived neurotrophic factor receptor alpha-like(GFRAL)pathway on the progression of atherosclerosis in ApoE-/-mice.Methods Eight 8-week-old male ApoE-/-mice were randomly divided into control group and rGDF-15 group.The mice in the control group received an injection of phosphate-buffered saline via tail vein once a week after 4 weeks of high-fat diet feeding,and those in the rGDF-15 group received an injection of recombinant GDF-15(0.05 mg/kg)via tail vein once a week after 4 weeks of high-fat diet feeding.The mice were fed with high-fat diet for another 8 weeks,the body weight was monitored during this period.After 12 weeks'feeding,the mice were euthanized.Another 4 normal mice(at the same age,20 weeks old)were subjected and served as normal control group.The levels of fasting blood glucose,blood lip-ids,cortisol,and aldosterone were compared among the three groups.Oil red O staining was used to evaluate plaque size in the aorta,and immunohistochemistry was employed to assess the expression of GDF-15 and GFRAL in the brain tissue.Results The serum level of GDF-15 was higher in the rGDF-15 group than in the control group(52.59±2.90 ng/ml vs 20.09±1.27 ng/ml,P＜0.01).The weight of mice was significantly lower in the rGDF-15 group than the con-trol group during Week 11(28.60±0.22 g vs 29.47±0.25 g,P＜0.01)and 12(28.98±0.22 g vs 30.35±0.13 g,P＜0.01).The rGDF-15 group had a statistically lower level of triglycerides(0.22±0.02 mmol/L vs 0.38±0.09 mmol/L,P＜0.05),lighter plaque burden[(22.22±2.58)％vs(31.61±3.51)％,P＜0.01],and enhanced expression levels of GDF-15 and GFRAL in the brain tissue(0.088±0.007 vs 0.030±0.006,0.031±0.003 vs 0.010±0.001,P＜0.01).The levels of cor-tisol and aldosterone in the control group and rGDF-15 group were significantly higher than those in the normal group(P＜0.01).The aldosterone level in the rGDF-15 group was significantly re-duced compared to the control group(22.013.67 mg/ml vs 87.29±8.63 mg/ml,P＜0.01).Conclusion GDF-15 may regulate body weight and triglyceride and aldosterone levels through GFRAL,and then affect the progression of atherosclerosis.

Objective: To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO. Methods: Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×10⁹/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×10⁹/L. Results: A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×10⁹/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×10⁹/L) at 4^th week, 8^th week and 12^th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×10⁹/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild. Conclusion Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

OBJECTIVETo compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF).

METHODThe authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on.

RESULT(1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival.

CONCLUSIONThe use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.

Adolescent ; Anemia, Aplastic ; drug therapy ; immunology ; mortality ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Infant ; Male ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Treatment Outcome