Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

Objective:To investigate the death of patients with granulocytopenia complicated with infection after chemotherapy and the changes of vital signs before emergency treatment, and to analyze the prognosis of different vital signs on patients' prognosis and emergency treatment.Methods:This study used a case-control study method to select 211 patients with hematologic malignancies who met the inclusion criteria in two tertiary hospitals in Weifang City. The vital signs of patients were collected and the vital signs were analyzed using SPSS 17.0 software. And the statistical significance and predictive value in the emergency response group.Results:The heart rate, respiratory rate, systolic blood pressure, blood oxygen saturation and urine volume were significantly different between the survival group (112 cases) and the death group (99 cases)( t values were 11.038-177.102, P<0.01). The area under the receiver operating characteristic curve of body temperature, heart rate, respiratory rate, systolic blood pressure, and blood oxygenation saturation and urine volume were 0.547, 0.495, 0.294, 0.899, 0.988, and 0.827, respectively. The highest predictive efficiency (higher level) was observed with the change of blood oxygen saturation, and the corresponding optimal cutoff point. 0.91; between the emergency treatment group (103 cases) and the non-emergency treatment group(108 cases), the difference in heart rate, respiratory rate and oxygen saturation between the two groups was statistically significant ( t values were 5.247, 8.001, 9.066, P<0.01). The area under the receiver operating characteristic curve of body temperature, heart rate, respiratory rate, systolic blood pressure, blood oxygen saturation and urine volume were 0.581, 0.732, 0.813, 0.346, 0.102, and 0.543, respectively. Among them, the predicted value of respiratory frequency change was the highest (medium level), which was the best corresponding. The cutoff point was 27.5. Conclusions:Patients with granulocytic infection after malignant hematologic disease will have abnormal changes in vital signs before death and emergency treatment. However, different vital signs have different effects on predicting disease changes, and should focus on respiratory rate and oxygen saturation. Changes, when the respiratory rate exceeds 27 beats/min, the probability that the patient needs to implement emergency treatment such as rescue will increase. If the condition is not effectively controlled, the blood oxygen saturation is lower than 0.91, the risk of death of the patient is greatly increased.

Objective:To investigate the clinical characteristics and change trend of patients with perianal lesions before or after Crohn′s disease (CD) diagnosed.Methods:From January 2008 to September 2018, at The Tenth People′s Hospital Affiliated to Tongji University, the clinical data of 747 hospitalized CD patients were retrospectively collected, 293 patients were PCD patients. The clinical characteristics of PCD patients before or after CD diagnosed were analyzed and the change trend was followed. T test, Mann-Whitney U test, and Chi-square test were performed for statistical analysis. Multivariate logistic regression analysis was used to analyze factors associated with perianal lesions onset time. Spearman correlation analysis was used to analyze the change trend of clinical characteristics. Results:Before CD diagnosis, 86.3% (253/293) PCD patients had perianal lesions. The median follow-up time (range) was 72 months (36 to 108 months). Compared with the patients presented with perianal lesions after CD diagnosis, the onset age of patients with perianal lesions before CD diagnosis was younger ((36.0±12.6) years vs. (24.2±10.2) years), and the rates of male (62.5%, 25/40 vs. 77.9%, 197/253), non-structuring and non-penetrating type (32.5%, 13/40 vs. 56.9%, 144/253) and perianal surgery (55.0%, 22/40 vs.76.7%, 194/253) were high, but low rate of abdominal surgery (37.5%, 15/40 vs. 13.0%, 33/253), and the differences were statistically significant ( t=2.630, χ2=4.442, 8.379, 8.379 and 15.081; all P<0.05). The results of logistic multivariate analysis showed that before CD diagnosis, non-structuring and non-penetrating type was more common than structuring type (odds ratio ( OR)=0.447, 95% confidence interval ( CI) 0.207 to 0.962, P=0.039) and penetrating type ( OR=0.264, 95% CI 0.089 to 0.780, P=0.016). The short disease duration of CD ( OR=0.981, 95% CI 0.968 to 0.995, P=0.008), structuring type ( OR=2.239, 95% CI 1.040 to 4.822, P=0.039) and penetrating type ( OR=3.788, 95% CI 1.281 to 11.198, P=0.016) were the risk factors of perianal lesions after CD diagnosed. The number of PCD patients ( r=0.964, P<0.01) and the proportion of biological agents ( r=0.879, P<0.01) increased with years, while PCD duration ( r=-0.828, P<0.01) and the rate of abdominal surgery significantly decreased with years ( r=-0.882, P<0.01). The proportion of biological agents was negatively correlated with the rate of abdominal surgery ( r=-0.770, P=0.006). Conclusions:The perianal lesions should be closely monitored in adult CD patients with short disease duration, structuring type and penetrating type for early diagnosis and treatment. Biological agents can improve the clinical outcomes of PCD.

Objective:To explore the role of infliximab (IFX) in the repairation of intestinal mucosal barrier in Crohn′s disease (CD).Methods:From January 2018 to October 2019, in Shanghai Tenth People′s Hospital, 382 CD patients were selected. All the patients were treated with IFX. And 103 individuals who underwent colonoscopy were selected as healthy control group. The general clinical data, fasting blood samples and intestinal mucosa tissue samples of CD patients and healthy controls were collected. The body mass index (BMI), hemoglobin, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and relative inflammation factors, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 and IL-17A, and their mRNA expression levels were detected. Crohn′s disease activity index (CDAI) and simplified endoscopic score for Crohn′s disease (SES-CD) were used to evaluate the disease activity of CD patients. The expression levels of occudin, claudin-1, zonula occluden-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were measured by Western blotting. The intestinal mucosal epithelial cells were observed by transmission electron microscope. T test was used for statistical analysis. Results:Before treatment, BMI, and hemoglobin and albumin levels of CD patients were all lower than those of healthy control group ((18.3±1.8) kg/m 2 vs. (20.2±1.2) kg/m 2, (95.3±8.4) g/L vs. (129.2±5.7) g/L, (33.2±5.4) g/L vs. (50.3±3.2) g/L), and the differences were statistically significant ( t=3.457, 5.342 and 2.674, all P<0.05). After treatment the BMI and hemoglobin levels of CD patients were higher than those before treatment ((19.5±2.1) kg/m 2 vs. (18.3±1.8) kg/m 2, (117.2±10.3) g/L vs. (95.3±8.4) g/L), and the CRP level, CDAI score and SES-CD score were lower than those before treatment ((16.3±2.3) mg/L vs. (47.2±9.3) mg/L, 113.2±12.5 vs. 245.2±23.5, 5.0±2.1 vs. 10.0±4.3), and the differences were statistically significant ( t=2.090, 2.339, 2.432, 6.345 and 5.234, all P<0.05). The expression levels of TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-17A and their mRNA levels of healthy control group were lower than those of CD patients before treatment ((1.1±0.4) ng/L vs.(158.2±38.3) ng/L, (3.2±0.8) ng/L vs. (28.3±13.4) ng/L, (2.7±1.3) ng/L vs. (3.3±2.4) ng/L, (5.2±0.3) ng/L vs. (16.3±7.4) ng/L, (16.3±6.3) ng/L vs. (18.9±10.2) ng/L, (10.5±2.3) ng/L vs. (38.5±11.2) ng/L; 1.00±0.00 vs. 4.68±0.34, 7.83±0.32, 1.25±0.46, 8.36±0.44, 2.01±0.89 and 6.83±0.53, respectively), and the differences were statistically significant ( t=2.345, 6.456, 3.008, 4.009, 7.045, 10.223, 8.345, 11.235, 1.114, 12.334, 5.304 and 5.678, all P<0.05). After treatment the TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-17A expression levels and their mRNA levels of CD patients were lower than those before treatment ((106.4±29.9) ng/L vs. (158.2±38.3) ng/L, (25.7±10.8) ng/L vs. (28.3±13.4) ng/L, (2.9±1.7) ng/L vs. (3.3±2.4) ng/L, (15.4±4.2) ng/L vs. (16.3±7.4) ng/L, (17.2±8.7) ng/L vs. (18.9±10.2) ng/L, (29.9±12.7) ng/L vs. (38.5±11.2) ng/L, 2.45±0.21 vs. 4.68±0.34, 3.75±0.18 vs. 7.83±0.32, 1.09±0.22 vs. 1.25±0.46, 3.78±0.21 vs. 8.36±0.44, 1.67±0.33 vs. 2.01±0.89, 2.96±0.11 vs. 6.83±0.53), and the differences were statistically significant ( t=9.345, 2.456, 2.334, 2.090, 3.009, 8.345, 4.567, 6.445, 2.046, 7.774, 3.008 and 8.867, all P<0.05). The results of Western blotting showed that the expression levels of occudin, claudin-1, ZO-1 and JAM-A in the intestinal mucosa of CD patients before treatment were lower than those of the healthy control group (0.21±0.03 vs. 1.00±0.02, 0.17±0.07 vs. 1.00±0.01, 0.16±0.06 vs. 1.00±0.04, 0.26±0.08 vs. 1.03±0.04). After treatment the expression levels of occudin, claudin-1, ZO-1 and JAM- A mRNA in the intestinal mucosa of CD patients were higher than those before treatment (0.77±0.08 vs. 0.21±0.03, 0.69±0.08 vs. 0.17±0.07, 0.78±0.09 vs. 0.16 ±0.06, 0.72±0.07 vs. 0.26±0.08), and the differences were statistically significant ( t=4.567, 6.346, 5.557, 8.456, 9.678, 8.671, 10.456 and 7.456, all P<0.05). Conclusions:IFX can effectively relieve the disease activity and improve the nutritional status of CD patients. IFX maintains the expression of intestinal epithelial tight junction protein by reducing inflammatory response, and repairs the intestinal mucosal barrier of CD patients.

Background:Malnutrition is common in inflammatory bowel disease,especially in Crohn' s disease (CD).Combined partial enteral and parenteral nutrition is effective for nutritional support in patients with severe CD.Aims:To investigate the effect of combined enteral and parenteral nutritional support on body composition and disease activity in severe active CD patients.Methods:A total of 72 patients with severe active CD admitted from July 2015 to August 2016 at Shanghai Tenth People' s Hospital were enrolled.In addition to conventional antibacterial and remission induction therapy,a combined partial enteral and parenteral nutritional support was given after admission.The nutritional status,body composition parameters and disease activity were evaluated and compared on admission and week 1,week 2 and week 3 of hospitalization.Results:The malnutrition rate was 100％ on admission,of which 90.3％ were severe malnutrition.After a 3-week combined enteral and parenteral nutritional support,the proportion of severe malnutrition decreased from 90.3％ to 34.7％ (P ＜0.05).Meanwhile,the body weight,body mass index,muscle mass,fat mass,protein content,and basal metabolic rate gradually increased and the disease activity index gradually decreased (P all ＜ 0.05).Conclusions:Combined enteral and parenteral nutritional support can improve the nutritional status and body composition parameters,reduce disease activity and induce remission effectively in severe active CD patients.

Objective To understand the malaria endemic characteristics and control measures in Caoxian County,Shan?dong Province,so as to summarize the experiences of malaria elimination. Methods The data of malaria endemic situation and control measures in Caoxian County from 1953 to 2014 were collected and descriptively analyzed,and the control effectiveness was evaluated. Results The incidence of malaria reduced from 13.25%in 1970 to 0.33%in 1983,and no malaria case was found in 1986. The goal of basic malaria elimination was achieved. The sporadic malaria infections were found from 2006 to 2010,and three imported malaria cases were found in Caoxian County from 2011 to 2014. Conclusion The effect of compre?hensive prevention and control measures taken in Caoxian County is significant,and the goal of malaria elimination has been reached. The imported malaria and secondary cases are future focuses of malaria control work.

Objective To explore the clinic character of immune thrombocytopenia (ITP) children infected with helicobacter py‐lori (Hp) and the effects of anti‐helicobacter pylori treatment on those children .Methods One hundred and forty‐two ITP children and 92 healthy children were conducted the 13C‐Urea breath test to determine the infections of Hp .The ITP children infected with Hp were divided into two groups :single drug group (48 cases ,treated only with corticosteroid ) and combined drugs group (49 ca‐ses ,treated with corticosteroid and anti‐helicobacter pylori treatment) .The platelet parameters ,platelet associated immunoglobulin and some lymphocyte subsets were analyzed .Results Ninety seven children infected with Hp were found in 142 ITP children (69 . 7% ) .In the mean time ,37 children infected with Hp were observed in 92 healthy children (40 .2% ) .After treatment of 6 months , the PLT ,PCT ,CD3+ ,CD3+CD4+ and CD3+ CD4+ /CD3+ CD8+ of ITP children in both group were increased ,and the increased degree of those parameters were much higher in combined drug group than those in single drug group (P< 0 .01) .However ,the MPV ,PDW ,PAIgG ,PAIgA and CD3+ CD8+ were more decreased than that of the single drug group(P<0 .01) .Conclusion The ITP children have a higher infection rate of Hp ,which may be involved in the pathogenesis of ITP .Anti‐helicobacter pylori therapy would improve the therapy efficacy of ITP children infected with Hp by improving their immunity .

Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Interferon-alpha ; Leukemia, Promyelocytic, Acute ; Tretinoin

Objective To evaluate the clinical feature of adult acute myeloid leukemia with nucleophosmin (NPM1) cytoplastic positive (NPMc+AML), and to investigate the significance of the NPM1 gene mutations regularly in detecting the early relapse. Methods The NPM1 gene mutations was screened by the PCR-capillary electrophoresis in 95 newly diagnosed adult AML patients. 5 complete remission AML patients were selected to detecte the NPM1 gene mutations regularly. Results In 95 cases of adult AML patients, the incidence of the NPM1 mutations was 9.5 % (28/95). The incidence of the NPM1 mutations in patients (≥40-year-old) was higher clearly than it' s in pazients (40-year-old) (λ 2= 6.963, P = 0.012). That in the AML patients with normal karyotype (51.1%) was higher than that in the patients with abnormal karyotype (8.3 %) (λ2= 20.860, P= 0.0000). NPM1 mutations occured with a considerate percentage in AML patients with M5/M2 subtype. In AML with recurrent genetic abnormalities the NPM1 mutations wasn' t found.The white blood cell count, platelet count, lactate dehydrogenase in the NPMc+AML patients were clearly higher than that in the NPMc-AML patients (t were individually 4.132, 4.603, 4.069, P ＜0.05). The rate of complete remission, relapse-free survival and overall survival in the NPMc+AML patients were also higher than that in the N PMc-AML patients (λ 2 were individually 10.448, 4.146, 4.384, P ＜0.05). In cases detected regularly NPM1 mutations preceded the hematological relapse about 1.5-2 months. Conclusion NPM1 gene mutations has a higher incidence in adult AML, particularly in normal karyotype AML. The clinical manifestations are older, and higher in white blood cell count, platelet count, and lactate dehydrogenase. The NPM1 mutations in adult AML is a good factor for prognosis. The regular detection of NPM1 mutation could find relapse early.

Objective To analyze expression of interleukin (IL)-23p19 and IL-23 receptor (IL-23R) in inflammatory bowel disease (IBD),and the role in the induction of peripheral blood T cell activation and proinflammatory cytokine secretion.Methods Peripheral blood (PB) and intestinal mueosal biopsies were collected from 12 patients with Crohn's disease (CD),25 patients with ulcerative colitis (UC) and 20 healthy controls.Expression of IL-23p19 was determined by immunohistochemistry and RT-PCR.IL-23R expression in CD4+,CD8+ T and NK cells from peripheral blood and lamina propria was analyzed by flow eytometry.Peripheral blood mononuclear ceils (PBMC) were isolated and cultured under stimulation with IL-23 and anti-CD3,and the levels of tumor necrosis factor α (TNFα) interferon (IFN)γ and IL-2 were determined by enzyme-linked immunosorbent assay (ELISA).Results The expression of II.-23p19 was significantly increased in inflamed mucosa of CD at both the transcriptional and translational levels compared with that in UC and healthy controls.IL-23R was mainly expressed in PB- and lamina propria-CD4+,CD8+T cells and NK cells from IBD patients,and markedly increased compared with controls (P＜0.05).IL-23 strongly triggered PBMC from IBD patients to produce significantly higher levels of IFN-γ,TNF-α and IL-2(P＜0.05).Conclusions IL-23p19 and IL-23R are highly expressed in IBD,particularly in CD,and may play an important role in the induction of T cell activation and proinflammatory cytokine secretion,suggesting that targeted therapy directed against IL-23 may have a therapeutic role in IBD.