Objective:To explore the protective effect and related mechanism of rebamipide on non-steroid anti-inflammatory drug (NSAID) related small intestinal mucosal injury.Methods:A total of 21 C57BL/6 mice were selected and by random number table method, they were divided into negative control group (0.9% NaCl gavage for four days), indomethacin modeling group (20 mg/kg indomethacin gavage for four days) and rebamipide intervention group (20 mg/kg indomethacin gavage for four hours and then 320 mg·kg -1·d -1 rebamipide gavage for four days), seven mice in each group. After modeling, the injury of mice intestinal mucosa of indomethacin modeling group and rebamipide intervention group was evaluated by gross observation as well as pathological analysis. The serum levels of interleukin (IL)-6, IL-10, trefoil factor 3 (TFF3), prostaglandin E2 (PGE2) and epidermal growth factor (EGF) in mice were detected by enzyme-linked immunosorbent assay (ELISA). The expression of IL-6, IL-10, TFF3, cyclooxygenase 2( COX2) and EGF at mRNA level of mice small intestinal tissues were examined by real-time quantitative polymerase chain reaction (qRT-PCR). And the relative expression of TFF3, COX2 and EGF at protein level of mice small intestinal tissues were determined by Western blotting. Levene test and independent sample t test were used for statistical analysis. Results:The scores of gross observation and histopathology of mice small intestinal mucosa injury of rebamipide intervention group were both lower than those of indomethacin modeling group (2.80±0.45 vs. 4.60±1.14, 1.67±0.52 vs. 3.00±0.71), and the differences were statistically significant ( t=2.667 and 3.618, P=0.029 and 0.006). The mouse serum level of IL-6 and the expression of IL-6 at mRNA level in intestinal tissues of indomethacin modeling group were both higher than those of the negative control group, however the serum level of IL-10 was lower than that of the negative control group ((48.83±5.40) ng/L vs. (40.96±5.92) ng/L, 5.23±2.36 vs. 1.12±0.56, (168.50±10.57) ng/L vs. (186.30±7.77) ng/L), and the differences were statistically significant ( t=2.307, 3.372 and 3.366; P=0.047, 0.007 and 0.012). The expression of IL-6 at mRNA level in mice small intestinal tissues of rebamipide intervention group was lower than that of indomethacin modeling group (1.74±0.82 vs. 5.23±2.36), however, the expression of IL-10 at mRNA level was higher than that of indomethacin modeling group (6.44±3.46 vs. 1.22±0.83), and the differences were statistically significant ( t=3.409 and 3.025, P=0.008 and 0.014). The serum levels of TFF3, PGE2 and EGF, the expression of TFF3 at mRNA level of small intestinal tissues, the relative expression of COX2 and EGF at protein level of small intestinal tissues of indomethacin modeling group were all lower than those of the negative control group ((131.20±16.37) ng/L vs. (150.30±9.66) ng/L, (32.68±6.88) ng/L vs. (41.51±3.20) ng/L, (112.70±17.17) ng/L vs. (138.20±10.10) ng/L, 0.43±0.22 vs. 1.20±0.50, 0.33±0.25 vs. 1.30±0.43, 0.28±0.19 vs. 1.15±0.10), and the differences were statistically significant ( t=2.290, 2.645, 2.867, 3.097, 3.405 and 7.106; P=0.048, 0.021, 0.025, 0.017, 0.027 and 0.002). The mice serum levels of PGE2 and EGF, expression of TFF3, COX2 and EGF at mRNA level of small intestinal tissues, as well as the expression of TFF3 and EGF at protein level of small intestinal tissues of rebamipide intervention group were all higher than those of indomethacin modeling group ((43.55±5.28) ng/L vs. (32.68±6.88) ng/L, (153.30±15.66) ng/L vs. (112.70±17.17) ng/L, 2.48±1.70 vs. 0.43±0.22, 2.95±1.56 vs. 0.88±0.45, 3.97±2.54 vs. 0.98±0.76, 1.47±0.26 vs. 0.72±0.35, 1.08±0.36 vs. 0.28±0.19), and the differences were statistically significant ( t= 2.711, 3.658, 2.656, 2.856, 2.524, 3.013 and 3.435; P=0.024, 0.008, 0.026, 0.019, 0.033, 0.039 and 0.026). Conclusions:Rebamipide alleviates small intestinal mucosal injury induced by indomethacin by inhibiting the expression of inflammatory factors and promoting the expression of intestinal mucosal protective factors suggesting that rebamipide plays a protective role in NSAID related small intestinal injury by maintaining the chemical barrier of the intestinal mucosal.

Objective To evaluate the performance of split-dosed polyethylene(PEG) for colonoscopy preparation.Methods Split-dose means that 1-3 L of PEG is taken in the afternoon or evening before examination and the remains in the next morning.And single-dose refers to all PEG is taken in the evening before ex-amination.A meta-analysis was conducted to compare bowel preparation quality,adenoma detection rate and patients' acceptance between groups.Results Ten randomized controlled trials were included into this study with 3 222 participants(1 481 in split-dose group and 1 741 in single-dose group).Split-dose group had higher rate of satisfactory bowel preparation(OR=3.37,95％CI:2.37-4.79),and so did the subgroup of 2～ 3 L PEG (OR =3.88,95％ CI:2.39-6.29).Split-dose group did not improve adenoma detection rate significantly (OR =0.94,95％ CI:0.71-1.24),but reported less adverse events such as nausea (OR =0.56,95％ CI:0.42-0.74)and vomiting(OR=0.51,95％CI:0.30-0.88).Conclusion Split-dosed PEG provides better colon cleansing with higher patient compliance,but does not improve detection rate of adenoma.

Objective To research the incidence and etiological factors of intraocular pressure(IOP)elevation in patients in early and late postop?erative stages after vitrectomy. Methods The clinical data of 235 cases(306 eyes)who underwent vitrectomy in our hospital were respectively ana?lyzed. IOP was measured before operation,in the early postoperative stage(within 2 weeks)and in the late postoperative stage(6 months after opera?tion or longer)by non?contact tonometer. Risk factors related with ocular hypertension happened in the early and late postoperative stages were statis?tically analyzed. Results The mean average IOP before operation was 15.3 ± 4.1 mmHg for the 306 eyes. Within the follow?up period of 6?20 months(mean,14.3 months),ocular hypertension occurred in 42 eyes[incidence,13.7%;mean,31.9 ± 6.0 mmHg]in the early postoperative stage and in 12 eyes[incidence,3.9%;mean,32.1 ± 5.7 mmHg]in the late postoperative stage. Logistic regression analysis revealed that lensecto?my,scleral buckling,cyclophotocoagulation,inert gas filling,silicone oil tamponade and diabetic retinopathy were the independent risk factors of oc?ular hypertension in early postoperative stage after vitrectomy,while lensectomy,scleral buckling,pan retinal photocoagulation,silicone oil tampon?ade,diabetic retinopathy and carotid artery stenosis were the independent risk factors of ocular hypertension in late postoperative stage after vitrecto?my. In addition,cyclophotocoagulation was a protective factor of IOP in the late postoperative stage. Conclusion The risk factors of ocular hyperten?sion after vitrectomy include the intraocular gapfiller,the mode of combined operation,disease type and carotid artery stenosis. IOP elevation that happens in the late postoperative stage is more harmful. Ocular hypertension in the late postoperative stage is not associated with that in the early stage.

ObjectiveTo investigate the variation of peripheral blood CD34+ cells during the hematopoietic stem cell mobilization,and its influence on the collecting timing and results.Methods Twenty-seven cases of peripheral blood hematopoietic stem cell mobilization and collection from April 2010 to December 2011 were analyzed,including 13 autologous cases mobilized with chemotherapy combined with granulocyte colony-stimulating factor (G-CSF,10 μg· kg-1 · d-1) and 14 cases of healthy donors mobilized with only G-SCF (7.5 μg · kg- 1 · d- 1 ).The number of peripheral blood CD34+ cells was counted,and its correlation with the yield of mononuclear cells (MNCs) and CD34+cells was analyzed.ResultsMNCs (5.84 ± 1.48) × 108/kg and CD34+ cells (3.93 ± 2.16) × 106/kg were obtained in healthy donors,and (6.58 ± 3.72) × 108/kg MNCs and (3.98 ± 3.06) × 106/kg CD34+ cells were obtained in autologous cases,respectively.There was only 1 failure in autologous cases.The peak of peripheral blood CD34+ cells in autologous cases appeared at day 4 after the treatment of G-CSF,and in healthy donors the number of peripheral blood CD34+ cells at day 5 was still in ascendant phase.The CD34+ cells/kg in the collection products were positively correlated with the percentage and absolute value of peripheral blood CD34+ cells.The cases ratio of CD34+ cells≥2× 106/kg in the products of single collection was up to 76.2％ (16/21) in the cases with peripheral blood CD34+ cells absolute value greater than 20/μl.ConclusionThe number of peripheral blood CD34+ cells was an important monitoring indicator in hematopoietic stem cell mobilization and collection,CD34+ cell absolute value ≥20/μl could be used as collection threshold.

Objective To study the immune re-constitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies.Methods From June 2011 to May 2015,65 patients with hematological malignancies were analyzed retrospectively.Lymphocyte subsets were determined by flow cytometry (FCM),including total T lymphocytes (CD3+),helper T cells (CD3+ CD4+),cytotoxic T cells (CD3+ CD8+),CD4/CD8 ratio,nature killer (NK) cells (CD3-CD56+),NKT cells (CD3+ CD56+),B lymphocytes (CD19+),naive T cells (CD3+ HLA-DR+),static T cells (CD3+ HLA-DR-),and regulatory T cells (CD4+ CD25high Foxp3+) on the day 14,28 and 42,and on the month 2,3,6,9,12,15,18 and 24 after allo-HSCT.Results The percentage of CD3+ T cells located normal range after hematological recovery,and its absolute number recovered to normal range at + 15 months.The percentage of CD3+ CD4+ T cells recovered to normal range at + 24 months.However,the absolute number of CD3+ CD4+ T cells did not recover to normal range until 24 months after allo-HSCT.The percentage of CD3+ CD8+ T cells was higher than normal range at + 42 day,and its absolute number was greater than normal range at + 3 months.Hence,low CD4/CD8 ratio was observed for a long period.The re-constitution time points of the percentage and absolute number of CD3+ HLA-DR+ T cells were + 3 months and + 24 months respectively.The re-constitution time points of the percentage and absolute number of CD3 + HLA-DR-T cells were + 2 months and + 15 months respectively.The re-constitution time points of the percentage and absolute number of regulatory T cells were + 12 months and + 15 months respectively.The percentage of NKT cells located in normal range after hematological recovery,and its absolute number retumed to normal range at + 12 months.The re-constitution time points of the percentage and absolute number of B cells were + 9 months and + 18 months respectively.The percentage of NK cells located in normal range after hematological recovery,and its absolute number returned nearly to normal range at + 3 months.Conditioning regimen containing ATG,source of stem cells,CD34+ cell number,GVHD,and CMV reactivation were all associated with immune re-constitution after allo-HSCT.Conclusion Different immune cells showed different re-constitution models after allo-HSCT,and the percentage recovered faster than absolute number for a certain kind of immune cells.Studying immune re-constitution and its associated factors may offer beneficial information for insight into transplantation immunology and improve the management of allo-HSCT.

Objective To explore the long-term outcomes and complications of patients with hematological malignancies (HM) after haploidentical donor transplantation (HDT) or siblingidentical donor transplantation (SDT).Methods From June,2011 to July,2016,89 patients with HM receiving allo-HSCT were retrospectively analyzed,including 57 patients undergoing HDT and 32 cases undergoing SDT.Results The median time to achieve neutrophil engraftment was 2 days shorter after HDT than SDT,whereas that of platelet engraftment was 3 days longer after HDT than SDT.The cumulative incidence for 3 to 4 grade acute graft-versus-host disease (GVHD) was not obviously different between HDT and SDT (8.77％ versus 12.5％ respectively;x2 =0.313,P =0.576).The cumulative incidence for chronic GVHD was not significantly different between HDT and SDT (45.6％ versus 37.5％;~ =0.551,P =0.458).Cytomegalovirus (CMV) reactivity was significantly higher in patients after HDT (77.19％) than those after SDT (21.88％) (x2 =25.633,P＜0.001).The occurrence of hemorrhagic cystitis was also obviously higher in patients after HDT (26.32％)than those after SDT (3.85％) (x2 =5.340,P =0.021).The 1-,2-,and 3-year relapse-free survival rate of patients receiving HDT and SDT was 63.9％,55.4％,44.3％ and 71.2％,58.3％,51.8％,respectively (P =0.541).The 1-,2-,and 3-year overall survival rate of patients receiving HDT and SDT was 75.3％,65.3％,52.3％ and 76.9％,62.9％,62.9％,respectively (P =0.777).Conclusion Considering similar incidence of severe GVHD and long-term outcomes,haploidentical donors should be recommended as a potential alternative donor source when an identical donor is lacking for patients with HM.

Chronic myeloid leukemia (CML) is a malignant tumor formed by clonal proliferation of bone marrow hematopoietic stem cells. With the improvement of disease awareness and the introduction of new drugs, more than 90% of CML patients can achieve long-term survival. However, a few patients still show drug resistance. This article reviews the mechanism of drug resistance in CML patients treated with tyrosine kinase inhibitor (TKI) and the characteristics of ABL kinase region mutation.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Objective:To explore immune cell reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT)by using mathematical function models.Methods:From June 2011 to May 2015, 65 patients with malignant hematological disorders were retrospectively analyzed. Immune cell frequencies and absolute counts were detected at day 14/28/42 and month 2/3/6/9/12/18/24 post-allo-HSCT. The immune cells included CD3 + T, CD4 + helper T, CD8 + effector T, regulatory T, CD19 + B, CD3 -CD56 + NK and CD3 + CD56 + NKT. Kinetic curve models and mathematical equations were established by utilizing curve model estimation. Results:Cubic curve models were observed for the changes of immune cell frequencies. Except for CD3 + T, CD8 + T and NK cells, the changes of absolute counts of immune cells conformed to cubic curve models. The reconstructed kinetic models of CD8 + T and NK cells after allo-HSCT were associated with relapse. Conclusions:Immune cell reconstitution after allo-HSCT conforms to certain mathematical function curve models. It may provide a new strategy for in-depth studies of immune reconstitution after allo-HSCT.

Objective:To explore the effects and underlying mechanisms of azintamide on gastric emptying and gastrointestinal hormone secretion in proton pump inhibitor related low gastric acid environment.Methods:A total of 60 rats were selected and randomly divided into low gastric acid control group, low gastric acid model group, low gastric acid and azintamide intervention group, high gastric acid control group, high gastric acid model group and high gastric acid and azintamide intervention group by random number table, with 10 rats in each group. The rats of low gastric acid control group and high gastric acid control group were all treated with 0.9% sodium chloride solution. The rats of low gastric acid model group and high gastric acid model group were established by intraperitoneal injection of 20 mg/kg omeprazole once per day for seven days, and subcutaneous injection of 2 mg/kg penta gastrin once per day for three days, respectively. The rats of low gastric acid and azintamide intervention group and high gastric acid and azintamide intervention group were gavaged with azintamide 50 mg/kg once per day for three days on the basis of low gastric acid model group and high gastric acid model group, respectively. Only the rats in three low gastric acid groups were analyzed. At Day 0, 2nd, 4th, 6th and 8th after modeling, the body weight of rats were compared. After modeling, the weight of gastric contents and pH of gastric fluid was measured and compared, and the peripheral blood levels of pepsinogen A (PGA), gastrin and cholecystokinin (CCK) were detected by enzyme linked immunosorbent assay. One-way analysis of variance and Tukey′s honestly significant difference post-hoc test were used for statistical analysis.Results:The pH value of gastric fluid in low gastric acid model group and low gastric acid and azintamide intervention group were both higher than that in the low gastric acid control group (2.17±0.53, 2.03±0.69 vs. 1.32±0.17), and the differences were statistically significant ( P=0.026 and 0.041, respectively). While there was no significant difference in pH value between the low gastric acid model group and low gastric acid and azintamide intervention group ( P>0.05). On the Day 0, 2nd, 4th, 6th and 8th after modeling, the body weight of rats of low gastric acid control group, low gastric acid model group and low gastric acid and azintamide intervention group was (285.40±10.86), (283.40±6.38), (282.00±5.04) g; (287.10±10.73), (283.20±5.83), (284.00±5.72) g; (292.20±11.18), (281.90±6.23), (289.00±5.82) g; (296.40±11.12), (277.70±6.96), (292.00±6.82) g; (300.80±11.29), (274.30±8.84), (297.00±4.17) g, respectively. On the Day 6th and 8th after modeling, the body weight of rats of low gastric acid model group was lower than that of the low gastric acid control group; and the body weight of rats of low gastric acid and azintamide intervention group was higher than that of low gastric acid model group, and the differences were statistically significant (both P<0.01). On the Day 0, 2nd, 4th, 6th and 8th, there was no statistically significant difference in body weight of rats between low gastric acid and azintamide intervention group and low gastric acid control group ( P>0.05). On the Day 0, 2nd, 4th, there were no statistically significant differences in body weight of rats between low gastric acid and azintamide intervention group and low gastric acid model group, and between low gastric acid model group and low gastric acid control group (both P>0.05). The weight of gastric contents of low gastric acid model group was heavier than that of low gastric acid control group ((2.36±0.11) g vs. (1.85±0.20) g), the weight of gastric contents of low gastric acid and azintamide intervention group was lighter than that of low gastric acid model group ((1.87±0.42) g vs. (2.36±0.11) g), and the differences were statistically significant ( P=0.019 and 0.016, respectively), and there was no statistically significant difference in weight of gastric contents between the low gastric acid and azintamide intervention group and the low gastric acid control group ( P>0.05). The peripheral blood level of PGA of rats of low gastric acid model group was lower than that of low gastric acid control group ((551.80±190.00) ng/L vs. (857.00±164.80) ng/L), while the peripheral blood level of PGA of the low gastric acid and azintamide intervention group was higher than that of the low gastric acid model group ((799.90±97.80) ng/L vs. (551.80±190.00) ng/L), and the differences were statistically significant ( P=0.011 and 0.037, respectively). There was no significant difference in peripheral blood level of PGA between the low gastric acid control group and the low gastric acid and azintamide intervention group ( P>0.05). The peripheral blood level of gastrin of the low gastric acid model group was higher than that of the low gastric acid control group ((49.31±11.93) ng/L vs. (35.59±5.29) ng/L), and the CCK level of the low gastric acid model group was lower than that of low gastric acid control group ((10.26±5.32) ng/L vs. (25.55±11.62) ng/L), and the differences were statistically significant ( P=0.037 and 0.035, respectively). The peripheral blood level of gastrin of the low gastric acid and azintamide intervention group was lower than that of low gastric acid model group ((35.65±6.49) ng/L vs. (49.31±11.93) ng/L), the level of CCK of the low gastric acid and azintamide intervention group was higher than that of low gastric acid model group ((27.59±11.22) ng/L vs. (10.26±5.32) ng/L), and the differences were statistically significant ( P=0.048 and 0.021, respectively). There were no significant differences in CCK and gastrin between low gastric acid and azintamide intervention group and low gastric acid control group (both P>0.05). Conclusion:Azintamide regulates the levels of gastrointestinal hormones CCK and gastrin under the condition of low gastric acid and affects the expression of pepsinogen A, thereby promoting gastric emptying in a low gastric acid environment.