Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Acetyl dipeptide-1 cetyl ester (AD-1) is a synthetic peptide composed of acetic acid and cetyl alcohol with arginine and tyrosine, which has certain anti-inflammatory and skin barrier enhancement effects, has been used in cosmetics for sensitive skin.Meanwhile, the ingredient has also been used in anti-aging cosmetics, but there is a lack of published scientific evidence on anti- senescence aspect.In this study, we investigated the related effects of AD-1 by evaluating its in vitro antioxidant and antiglycation efficacies.Furthermore, we established a photoaging model on primary rat dermal fibroblasts by repeated exposures to UVA irradiation.MTT assay was used to detect the effects of AD-1 on the cell viability.RT-qPCR was used to determine the effects of AD-1 on the mRNA levels of senescence-related p21, p53, MMPs, IL6, Col1, Col3 and autophagy-related p62, ATG5, ATG7.Western blot was used to detect the effects of AD-1 on the protein levels of p16, p21, p53, Col1, LC3B and p62.SA-β-gal was performed to indicate senescence level of the cell.MDC was performed to indicate autophagy level.Intracellular reactive oxygen species were monitored by fluorescent probes DCFH-DA.The results showed that AD-1 could reduce UVA-induced the cell damage and regulate the abnormal expression of mRNA levels. It alleviated the abnormal protein levels of p16, p21, p53, Col1, LC3B and p62 induced by UVA. These results suggested that AD-1 has not only antioxidant and antiglycation effects but also can activate autophagy to achieve anti-senescence effect.

Objective To analyze the clinical features and clinical significance of patients with inflammatory bowel disease (IBD) complicated by thrombosis.Methods From March 14th,2001 to February sixth 2017,at Nanjing General Hospital of Nanjing Military Command,27 IBD patients with thrombosis diagnosed by clinical symptoms,endoscopy,imaging and pathology were enrolled.During the same period,81 gender and age matched IBD patients without thrombosis were included in the control group.The basic data,information of IBD diagnosis and treatment and thrombotic events of patients were collected and analyzed.T-test and Chi-square test were performed for statistical analysis.Binary logistics regression was used for risk factors analysis.Results The mean age of diagnosis of IBD patients with thrombosis was (44.8 ± 15.8) years,which was higher than that of the IBD patients of control group ((36.0 ± 14.4) years),and the difference was statistically significant (t =2.69,P =0.008).Among 27 IBD patients with thrombosis,arterial thrombosis was 51.9％ (14/27),deep venous thrombosis of the lower extremity veins was 29.6％ (8/27),portal venous system involved was 11.1％ (3/27),pulmonary embolism was 3.7％ (1/27) and disseminated intravascular coagulation accounted for 7.4％ (2/27).Nine patients (33.3％,9/27) underwent surgery six months before the diagnosis of thrombosis.The results of binary logistic regression indicated that the age of diagnosis and vascular catheterization were independent risk factors for thrombosis in IBD patients (odds ratio (OR) =1.04,95％ confidence interval (CI) 1.01 to 1.07,P=0.01;0R=5.64,95％ CI 1.39 to 22.96,P=0.02).After medicine treatment or surgery,81.5％ (22/27) of the patients improved,9.1％ (2/22) were worse and 13.6％ (3/22) died.Conclusion Screening and prevention of thrombosis should be paid attention in IBD patients with a history of vascular catheterization,at active phase and older age when diagnosed.

Objective: To examine the relative factors of transmural intestinal necrosis(TIN) during multidisciplinary stepwise management facilitating the decision making in patients with acute superior mesenteric vein thrombosis (ASMVT). Methods: Clinical data of patients with ASMVT admitted to Department of General Surgery, Jinling Hospital from January 2009 to June 2017 were reviewed retrospectively. There were 52 males and 37 females, aging (45.9±12.6) years (range: 20 to 69 years). According to the postoperative pathological results and follow-up, the patients were divided into TIN group (n=31) and non-TIN group(n=58, including 18 cases of intestinal stricture). The related factors were compared between ASMVT patients with TIN and patients without TIN by univariate analysis using t test, U test and χ² test accordingly, and factors with statistically significance were subsequently submitted to binary Logistic regression analysis. The predictive value and cut-off point of factors were evaluated by receiver operator characteristic(ROC) curve and area under the curve. Results: In univariate analysis, smoking, hypertension, peritonitis, white blood cell count,haemoglobin, international normalized ratio, blood albumin, thrombosis of superior mesenteric branches vein, free intraperitoneal fluid, decrease of bowel wall enhancement and pneumatosis intestinalis were TIN risk factors (all P<0.05). According to the binary Logistic regression analysis, white blood cell count (OR=1.093, 95%CI: 1.010 to 1.182, P=0.027), thrombosis of the superior mesenteric branches vein (OR=11.519, 95%CI: 1.906 to 69.615, P=0.008), pneumatosis intestinalis (OR=11.140, 95%CI: 2.360 to 52.585, P=0.002) were independent relative factors of TIN in patients with AMI, and the area under the ROC curve of the above factors and predictive model was 0.759 (95%CI: 0.647 to 0.871), 0.745 (95%CI: 0.641 to 0.848), 0.737 (95%CI: 0.621 to 0.854), 0.909 (95%CI: 0.847 to 0.971), respectively. The cutoff value of white blood cell count was 18.1×10⁹/L. Conclusion White blood cell levels, superior mesenteric vein branch thrombosis and pneumatosis intestinalis are independent predictors of TIN in ASMVT.

Objective To examine the relative factors of transmural intestinal necrosis(TIN) during multidisciplinary stepwise management facilitating the decision making in patients with acute superior mesenteric vein thrombosis (ASMVT). Methods Clinical data of patients with ASMVT admitted to Department of General Surgery, Jinling Hospital from January 2009 to June 2017 were reviewed retrospectively. There were 52 males and 37 females, aging (45.9 ± 12.6) years (range: 20 to 69 years). According to the postoperative pathological results and follow?up, the patients were divided into TIN group (n=31) and non?TIN group(n=58, including 18 cases of intestinal stricture). The related factors were compared between ASMVT patients with TIN and patients without TIN by univariate analysis using t test, U test and χ2 test accordingly, and factors with statistically significance were subsequently submitted to binary Logistic regression analysis. The predictive value and cut?off point of factors were evaluated by receiver operator characteristic(ROC) curve and area under the curve. Results In univariate analysis, smoking, hypertension, peritonitis, white blood cell count,haemoglobin, international normalized ratio, blood albumin, thrombosis of superior mesenteric branches vein, free intraperitoneal fluid, decrease of bowel wall enhancement and pneumatosis intestinalis were TIN risk factors (all P<0.05). According to the binary Logistic regression analysis, white blood cell count (OR=1.093, 95%CI: 1.010 to 1.182, P=0.027), thrombosis of the superior mesenteric branches vein ( OR=11.519, 95%CI : 1.906 to 69.615, P=0.008), pneumatosis intestinalis ( OR=11.140, 95%CI : 2.360 to 52.585, P=0.002) were independent relative factors of TIN in patients with AMI, and the area under the ROC curve of the above factors and predictive model was 0.759 (95%CI : 0.647 to 0.871), 0.745 (95%CI : 0.641 to 0.848), 0.737 (95%CI : 0.621 to 0.854), 0.909 (95%CI: 0.847 to 0.971), respectively. The cutoff value of white blood cell count was 18.1×109/L. Conclusion White blood cell levels, superior mesenteric vein branch thrombosis and pneumatosis intestinalis are independent predictors of TIN in ASMVT.

Objective To examine the relative factors of transmural intestinal necrosis(TIN) during multidisciplinary stepwise management facilitating the decision making in patients with acute superior mesenteric vein thrombosis (ASMVT). Methods Clinical data of patients with ASMVT admitted to Department of General Surgery, Jinling Hospital from January 2009 to June 2017 were reviewed retrospectively. There were 52 males and 37 females, aging (45.9 ± 12.6) years (range: 20 to 69 years). According to the postoperative pathological results and follow?up, the patients were divided into TIN group (n=31) and non?TIN group(n=58, including 18 cases of intestinal stricture). The related factors were compared between ASMVT patients with TIN and patients without TIN by univariate analysis using t test, U test and χ2 test accordingly, and factors with statistically significance were subsequently submitted to binary Logistic regression analysis. The predictive value and cut?off point of factors were evaluated by receiver operator characteristic(ROC) curve and area under the curve. Results In univariate analysis, smoking, hypertension, peritonitis, white blood cell count,haemoglobin, international normalized ratio, blood albumin, thrombosis of superior mesenteric branches vein, free intraperitoneal fluid, decrease of bowel wall enhancement and pneumatosis intestinalis were TIN risk factors (all P<0.05). According to the binary Logistic regression analysis, white blood cell count (OR=1.093, 95%CI: 1.010 to 1.182, P=0.027), thrombosis of the superior mesenteric branches vein ( OR=11.519, 95%CI : 1.906 to 69.615, P=0.008), pneumatosis intestinalis ( OR=11.140, 95%CI : 2.360 to 52.585, P=0.002) were independent relative factors of TIN in patients with AMI, and the area under the ROC curve of the above factors and predictive model was 0.759 (95%CI : 0.647 to 0.871), 0.745 (95%CI : 0.641 to 0.848), 0.737 (95%CI : 0.621 to 0.854), 0.909 (95%CI: 0.847 to 0.971), respectively. The cutoff value of white blood cell count was 18.1×109/L. Conclusion White blood cell levels, superior mesenteric vein branch thrombosis and pneumatosis intestinalis are independent predictors of TIN in ASMVT.

Objective To explore the diagnosis and treatment of mesenteric venous thrombosis secondary to long-term ischemic enteropathy.Methods The retrospective cross-sectional study was conducted.The clinical data of 36 patients with mesenteric venous thrombosis secondary to long-term ischemic enteropathy who were admitted to the Nanjing General Hospital of Nanjing Military Command from January 2009 to June 2017 were collected.Diagnostic methods:history inquiry,physical examination,laboratory test and image finding.Treatment methods:parenteral nutrition support,selective stage 1 bowel resection with anastomosis or stage 1 bowel resection and colostomy,definitive stage 2 operation for recovering digestive tract.Anticoagulation therapy was performed.Observation indicators:(1) clinical characteristics;(2) treatment;(3) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect postoperative complications up to December 2017.Measurement data with skewed distribution were described as M (P25,P75) and M (range).Results (1) Clinical characteristics:① the main clinical manifestations:34,33,27,20,17 and 14 patients showed respectively discomfort after meal,abdominal pain,abdominal distension,nausea with vomiting,stop of analis exhaust and defecation and weight loss of different degree,and the worst patient lost 20 kg within 1 month.The clinical manifestations of 30 patients were more than 3.② The score of acute physiology and chronic health evaluation (APACHE)Ⅱ in 36 patients was 4 (2,6).③ Laboratory test:total protein (TP),albumin and prealbumin were 55.8 g/L (45.2 g/L,59.1 g/L),30.6 g/L (27.3 g/L,37.5 g/L) and 100.0 g/L (86.0 g/L,132.0 g/L),respectively,showing a decreased trend.④ Imaging finding:enhanced scans of abdominal CT showed the portal cavernous in 16 patients,the absence of main trunk of superior mesenteric vein with extensive collaterals in 12 patients,and dovelopment of portal vein and main trunk of superior mesenteric vein in 8 patients.One patients had intestinal edema and stenosis.X-ray contrast examination of digestive tract showed intestinal stenosis with mucosal erosion in 28 patients and complete intestinal obstruction in 8 patients.(2) Treatment:of 36 patients,24 underwent stage 1 bowel resection with anastomosis and other 12 received stage 1 bowel resection and colostomy (11 undergoing definitive stage 2 operation for recovering digestive tract and 1 refusing stage 2 operation due to advanced age).The length of resected bowel was 30 cm (15 cm,80 cm).One patient with stage 1 bowel resection with anastomosis was complicated with small bowel fistula,and was cured by conservative treatment.There was no complication in other patients.(3) Follow-up:all 36 patients were followed up for 3-10 months,with a median time of 6 months.During the follow-up,7 patients were complicated with secondary portal hypertension,5 of 7 were improved by symptomatic treatment,and 2 died of severe digestive tract bleeding;other patients had no related complications.Conclusions The discomfort after meal and bowel obstruction are the main clinical manifestations of mesenteric venous thrombosis secondary to long-term ischemic enteropathy.The abdominal CT with X-ray contrast examination benefits to diagnosis of patients with poor nutrition status and mild infection.The main strategy includes early surgical resection and postoperative anticoagulation therapy after bleeding risk evaluation.

Objective To investigate the influential factors of surgical treatment for ischemic enteropathy secondary to portal venous system thrombosis (PVST).Methods Clinical data of 27 patients with ischemic enteropathy secondary to PVST admitted in our department from January 2009 to Jun 2016 were analyzed retrospectively.These patients were divided into two groups according to different surgical procedures:ischemic bowel resection with primary anastomosis or ostomy.Results There were significant differences between the groups in albumin and prealbumin level (t =3.585,4.194,P ＜0.05).There were also significant differences for BMI and body fat (t =2.325,2.430,P ＜ 0.05).The average time from the onset PVST to ischemic enteropathy was 20 d.Conclusion There should be awareness of ischemic enteropathy.Intestinal resection and anticoagulation therapy is necessary.The choice of surgical procedures depends on the preoperative nutrition level (albumin,prealbumin).

Objective: To evaluate the application of intestinal stomas in mesenteric ischemia (MI) according to the concept of damage control surgery. Methods: Clinical data of 59 MI patients received intestinal stomas at Jinling Hospital, Nanjing University School of Medicine from January 2010 to June 2017 were analyzed retrospectively. There were 41 male and 18 female patients aging of (51±14) years (ranging from 20 to 86 years). All the patients were divided to two groups according to the degree of bowel ischemia: acute MI group (AMI, bowel necrosis, n=43) and chronic MI group (CMI, bowel stricture, n=16). The medium time from onset to consult of AMI was 7(12) days (M(Q_R)) and the time of CMI was 80(51) days. After the resection of irreversible ischemic intestine, ostomy was carried out for all 59 patients. Patients received oral anticoagulation, enteral nutrition and succus entericus reinfusion therapy for about 6 months after discharge. Then definite surgery to restore digestive tract was preferred. Results: In AMI group, APACHEⅡ score in admission was (16±3). The length of infarcted intestine resected was (160±95) cm, normal bowel left was (220±106) cm. Twelve patients had complications during first post-operation period including sepsis (n=8), acute renal failure (n=4), acute respiratory distress syndrome (n=4), short bowel syndrome (n=4). 30-day mortality was 18.6%. Total 30 patients received operation to restore the continuity of intestinal tract after 202(42) days and APACHEⅡ score was 4±2. Two patients suffered from sepsis and were cured after anti-infection. In CMI group, APACHEⅡ score was 16±3 and NRS2002 score was more than 3. The length of infarcted intestine resected was (43±33) cm. All patients had restored the continuity of intestinal tract after 176 (47) days. No major complications occurred during the first and second post-operation period. Conclusions According to damage control surgery, after early revascularization, patients with acute intestinal necrosis should be treated with infarcted bowel resection and stomas. Besides, second operation to restore the continuity of intestinal tract should be conducted after nutritional support for 6 months. Patients with ischemic enteropathy who cannot be corrected with severe malnutrition should achieve stomas during first operation.

OBJECTIVETo observe the efficacy of chemotherapy consisted of bortezomib as main druy in maintenance therapy for recurrence of newly diagnosed MM patients.

METHODSThe clinical data and outcome of 37 MM patients during 2008-2013 were analyzed retrospectively, the 37 MM patients were divided into 2 group: 19 cases including 13 cases of newly diagnosed MM with symptoms and 6 cases of relapsed refractory MM were enrolled in group A; 17 cases of newly diagnosed MM with symptoms were enrolled in group B. The patients of group A received maintenance therapy consisted of bortezomib plus dexamethasone (VD group), while the patient group B received maintenance therapy consisted of melphalan plus prednisone(MP group), then the therapeutic efficacy of 2 group was compared.

RESULTSThe overall response rate(ORR) in VD groupe was 84.2%(16/19), out of which CR rate reached 42%(8/19), PR rate reached 31.6%(6/19), MR rate reached 10.5%(3/19). During median follow-up for 21.8(5-51) months, death occurred, while the ORR in MP group was 52(9/17), out of which CR rate was 23.5%(4/17), PR rate reached 23.5%(4/17), MR rate reached 5.9%(1/17). Druing median follow-up for 16.4(4-39) months, the worteity reaced 64.7%(11/17). The differencr between 2 groups was significant(P<0.05). The median OS time of patients in VD group was 21.6 months, that in MP group was 17.9 months(P<0.05). The median PFS in VD group and MP group were 13.4 and 9.4 months respectively(P<0.001).

CONCLUSIONThe ORR and CR rates of bortezomib maintenance therapy for newly diagnosed and relapsed / refractory MM patients are very high, and its toxicity can be controlled, therefore, the patients need maintenance therapy after remission.