Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective:To investigate the effectiveness and feasibility of a 3D U-Net in conjunction with a three-phase CT image segmentation model in the automatic segmentation of GTVnx and GTVnd in nasopharyngeal carcinoma.Methods:A total of 645 sets of computed tomography (CT) images were retrospectively collected from 215 nasopharyngeal carcinoma cases, including three phases: plain scan (CT), contrast-enhanced CT (CTC), and delayed CT (CTD). The dataset was grouped into a training set consisting of 172 cases and a test set comprising 43 cases using the random number table method. Meanwhile, six experimental groups, A1, A2, A3, A4, B1, and B2, were established. Among them, the former four groups used only CT, only CTC, only CTD, and all three phases, respectively. The B1 and B2 groups used phase fine-tuning CTC models. The Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95) served as quantitative evaluation indicators.Results:Compared to only monophasic CT (group A1/A2/A3), triphasic CT (group A4) yielded better result in the automatic segmentation of GTVnd (DSC: 0.67 vs. 0.61, 0.64, 0.64; t = 7.48, 3.27, 4.84, P < 0.01; HD95: 36.45 vs. 79.23, 59.55, 65.17; t = 5.24, 2.99, 3.89, P < 0.01), with statistically significant differences ( P < 0.01). However, triphasic CT (group A4) showed no significant enhancement in the automatic segmentation of GTVnx compared to monophasic CT (group A1/A2/A3) (DSC: 0.73 vs. 0.74, 0.74, 0.73; HD95: 14.17 mm vs. 8.06, 8.11, 8.10 mm), with no statistically significant difference ( P > 0.05). For the automatic segmentation of GTVnd, group B1/B2 showed higher automatic segmentation accuracy compared to group A1 (DSC: 0.63, 0.63 vs. 0.61, t = 4.10, 3.03, P<0.01; HD95: 58.11, 50.31 mm vs. 79.23 mm, t = 2.75, 3.10, P < 0.01). Conclusions:Triphasic CT scanning can improve the automatic segmentation of the GTVnd in nasopharyngeal carcinoma. Additionally, phase fine-tuning models can enhance the automatic segmentation accuracy of the GTVnd on plain CT images.

Objective:To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection.Methods:This multicenter cross-sectional parallel control study was conducted in 11 children′s hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman′s rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection.Results:A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum ( r=0.97 , P<0.01). The linear regression equation was PCT?venous serum=0.135+0.929×PCT peripheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods ( r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. Conclusions:There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

Objective:To explore ultrasonographic diagnostic characteristics of ovarian epithelial tumors and establish prediction models.Methods:The ultrasonographic images of 427 cases from multicenter with ovarian epithelial tumors confirmed by pathology from January 2015 to July 2019 were retrospectively analyzed according to the International Ovarian Tumor Analysis (IOTA). Ultrasonographic signs with distinguishing significance were obtained through univariate analysis and included into multivariate Logistic regression analysis to obtain important ultrasonagraphic indicators for distinguishing borderline, benign and malignant ovarian tumors, and to establish prediction models.Results:The microcystic pattern of papillary projections and solid components was the diagnostic characteristic between borderline and benign, malignant ovarian epithelial tumors( OR value 10.97 and 19.22, respectively). Irregular morphology, septa thickness, solid lesions, rich blood supply and ascites were diagnostic characteristics between benign and malignant tumors, with the irregular morphology having the highest value. Irregular morphology, large papillary, septa thickness and rich blood supply could be used to identify borderline and malignant tumors. At the same time, irregular morphology was the valuable sign to distinguish borderline and benign tumors. In this study, the total coincidence rate of the proposed model was 72.4%, among which the predicted coincidence rate of the borderline model was 57.2%, 78.6% for benign, and 80.7% for malignant. Conclusions:The microcystic pattern of papillary projections and solid components are the specific sonographic characteristics of borderline ovarian tumors. Irregularity, solid lesions, rich blood supply and ascites have important value in differentiating ovarian epithelial tumors. The prediction models of benign, malignant and borderline ovarian tumors in this study have higher diagnostic efficacy.

OBJECTIVE：To introduce the development and application of automatic dosing and mixing system of intravenous infusion in PIVAS of our hospital. METHODS ：Based on the bar code management system in PIVAS ，combined with automatic mixing equipment ，our hospital developed and designed automatic dosing and mixing system of intravenous infusion which could realize real-time scanning and charging of drugs ，setting parameters of mixed dispensing and automatic dosing and mixed dispensing of intravenous infusion. Compared with manual dispensing model ，work efficiency of 5 staff who dispensed Coenzyme complex for injection and Carbazochrome sodium s ulfonate for injection 300 bags each as well as the amount of drug residues in empty bottle were investigated to evaluate the effects of the system. RESULTS ：The system realized automatic mixing of intravenous infusion. In manual dispensing model and automatic dispensing model ，the mixing efficiency of Coenzyme complex for injection were （96.6±10.0）and（195.2±10.7）bag/h（P＜0.001）；mixing efficiency of Carbazochrome sodium sulfonate for injection were （83.8±12.9）and（118.8±6.7）bag/h（P＜0.001）. The amount of residual liquid in Coenzyme complex for injection empty bottle were （0.09±0.02）and（0.11±0.01）mL；Carbazochrome sodium sulfonate for injection empty bottle were （0.08± 0.02）and（0.12±0.01）mL，which were all lower than the internal control requirements that injected solvent volume was no more than 5％ （0.15 mL）. CONCLUSIONS ：The automatic dosing and mixing system of intravenous infusion could improve the efficiency of intravenous infusion dispensing and reduce the labor intensity of the staff .

OBJECTIVE：To provide refe rence for inte lligent managemen t of central pharmacy. METHODS ：The construction experience of intelligent central pharmacy management mode were introduced ，including the use of information technology ，the introduction of automation equipment ，the rational layout of the central pharmacy ，as well as the optimization of work flow ，and the establishment of integrated management mode ，etc. The workload of intelligent central pharmacy in our hospital before construction（2016），during construction （2017-2018）and after operation （2019）were collected from our hospital information system（HIS），including the number of injection doctor ’s orders ，the number of doctor ’s orders reviewed ，the number of PIVAS deployment，the number of oral medical orders ，the number of medical orders discharged with medicine ，etc. The pharmacist scheduling before and after the operation of intelligent central pharmacy in our hospital was counted. The average daily quantity of injection prescription ，average dispensing speed ，timely delivery rate and dispensing errors were calculated. In addition ，the satisfaction of medical staff in 39 wards of our hospital were investigated every quarter to evaluate the implementation effect of intelligent central pharmacy management model. RESULTS ：From 2016 to 2019，the workload of the central pharmacy in our hospital showed an overall upward trend ，and the average daily prescription amount increased year by year ，and the average daily prescription amount in 2017-2019 was significantly more than that in 2016（P＜0.05）. Average dispensing speed ，timely delivery rate and dispensing errors of central pharmacy during 2018-2019 were significantly lower than 2016（P＜0.05）. The daily number of pharmacists in dispensing posts in the central pharmacy was reduced from 22 in 2016 to 18 in 2019，with 4 pharmacists saved. During the 4 years，867 questionnaires were distributed and 862 valid questionnaires were recovered. The effective recovery rate was above 99％. The average satisfaction of medical staff in the ward to the central pharmacy was high relatively ，being 96.8％， 98.4％ ，99.1％ and 99.1％ respectively from 2016 to 2019. CONCLUSIONS ：The integrated intelligent center pharmacy management mode established in our hospital has realized the information and automatic management of inpatient medication order dispensing；reasonable arrangement of the work contents of professional and technical personnel with different professional titles can not only save the labor cost ，but also increase the content 09304021） of pharmaceutical care ，broaden the work depth ，so as to improve the work efficiency and ensure the quality of 126.com pharmaceutical care.

Objective To explore the potential effects of neutrophil extracellular traps (NETs) on rheumatoid arthritis synovial fibroblasts (RA-FLSs).Methods The synovial tissues of RA patients were isolated and cultured in vitro.Peripheral blood neutrophils were extracted from healthy volunteers and used to stimulate NETs' formation,following with NETs' extraction.MTS proliferation assay was used to evaluate the effect of NETs on the proliferation of RA-FLSs.QRT-polymerase chain reaction (q-PCR) was used to determine the expression of connective tissue growth factor (CTGF) mRNA in cells treated with NETs-stimulated RA-FLSs for 60 h.The results were processed using paired sample t-test and one-way analysis of variance (ANOVA).Results The isolated and purified neutrophils could form NETs by in vitro stimulation.The concentration of extracted NETs-DNA was 58.5 ng/μl (1×106 cells).Compared with the control group (0 μl NETs),NETs could promote the proliferation of RA-FLSs.With the increase of NETs' concentration,the proliferation of RA-FLSs was also enhanced (F=99.519,P＜0.05).Compared with the control group (0 μl NETs),10 μl NETs could significandy promote the proliferation of RA-FLSs (t=-12.226,P＜0.01).Pretreatment of NETs with DNase Ⅰ inhibited its effect on promoting the proliferation of RA-FLSs (t=-2.376,P=0.049),NETs stimulated the upre-gulation of CTGF mRNA expression in RA-FLSs [(30.7±0.5),t=12.13,P＜0.01].Conclusion NETs can promote the proliferation of RA-FLSs and stimulate the up-regulation of CTGF mRNA in RA-FLSs in vitro.

OBJECTIVE： To improve the quality of antitumor drug dispensing in pharmacy intravenous admixture services （PIVAS）， reduce dispensing error and occupational exposure to dispensers by antitumor drugs. METHODS： The composition and functions of automatic injection dispensing system were introduced， and the system was applied in antitumor drug dispensing in PIVAS. Various work indexes were compared 1 month before and after the application of the system. RESULTS： The system included information processing software， equipment control software and drug dispensing machine hardware， and had functions such as automatic counting of medicines， automatic entry into basket， automatic drug dispensing and automatic printing of labels. After applying automatic injection dispensing system， the operation of infusion label printing， basket dividing and dispensing in dispensing process was changed from manual to automatic. It could save human resources， as for each label， the average time of drug dispensing decreased from （33.00±3.31） s to （15.55±1.41） s while no mistakes and damaged label was found. CONCLUSIONS： The application of automatic injection dispensing system achieves automatic operation of antitumor drug dispensing in PIVAS， reduce dispensing error reduces staff’s exposure to antitumor drugs and occupational exposure.

Objective To investigate the possible differences in safety and efficacy between re-use and initial use in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor inhibitors (TNFi). Methods From October 2016 to October 2017, 82 patients with AS who were admitted to the Second Hospital of Lanzhou University were studied. Among them, 57 patients used TNFi for the first time and 25 patients reuse it after the interruption. After 3 months of standardized use of TNF-inhibitor, we compared the efficacy indicators [visual analogue scale/score (VAS), morning stiffness, bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis metroloty index (BASMI), ankylosing spondylitis disease activity score (ASDAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) 0 and safety events between the two groups. T test and covariance analysis were used. Results The efficacy indexes of the two groups after treatment were significantly improved, the difference was statistically significant (P<0.05) compared with the baseline [Before and after treatment in the first treatment group: ESR: (40±31) mm/1 h, (8±8) mm/1 h, CRP: (28±35) mg/L, (5±9) mg/L, VAS: (6.5±1.6), (2.0 ±1.7), Morning stiff time: (0.6 ±0.4) h, (0.1 ±0.2) h, BASDAI: (5.0 ±1.3) h, (1.6 ±1.2) h, BASFI: (4.1 ±2.3), (1.3±1.3), BASMI: (2.6±2.0), (0.8±1.0), ASDAS: (3.5±0.8), (1.2±0.7); Before and after treatment in the re-use group: ESR: (39 ±33) mm/1 h, (9 ±10) mm/1 h, CRP: (28 ±28) mg/L, (5 ±6) mg/L, VAS: (6.6 ±1.9), (1.6 ±1.0), Morning stiff time:(0.6±0.4) h, (0.1±0.1) h, BASDAI:(5.1±0.8), (1.4±1.4), BASFI (5.1±2.2), (1.3±1.4), BASMI:(3.4 ±1.8), (1.0 ±0.9), ASDAS: (3.6 ±0.8), (1.2 ±0.4)]. But there was no statistical significant difference between the two groups in patients after treatment (P>0.05). Conclusion Patients with AS who re-uses TNFi after discontinuation could achieve the same safety and efficacy as they first use it.

Objective To study the function of interleukin (IL)-25 for rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) differentiation as well as on the expression of extracellular regulating protein kinase (ERK) and matrix metalloproteinases-3 (MMP-3).Methods The differences on ERK1/2 and MMP-3 protein levels were tested in RA-FLS of RA patients and healthy controls,then IL-17A (10 ng/ml) was tested when the RA-FLS were co-stimulated with different concentrations of IL-25 (0.01,0.1,1 and 10 ng/ml) and IL-17A(10 ng/ml) for 24 hours respectively.The expression of ERK1/2 and MMP-3 protein was detected by the Western blot.T test was used for the comparison between different groups.Results The expression of ERK1/2 (1.71±0.17) and MMP-3 (0.50±0.13) proteins in RA-FLS was higher than the healthy controls (0.50±0.15,0.17±0.05) (t=-9.13,P＜0.01 and t=-4.10,P＜0.05),after stimulated with IL-17A,the expression of ERK1/2 (0.77±0.22) and MMP-3 (0.59±0.13) proteins in RA-FLS were increased compared with the untreated groups (0.18±0.35,0.04±0.03) (t=-4.69,P＜0.01 and t=-7.47,P＜0.01).With increase of the concentration on IL-25,the level of ERK1/2 (0.54±0.26,0.48±0.18,0.48±0.23,0.23±0.06) and MMP-3 (0.58±0.09,0.59±0.14,0.21±0.04,0.04±0.02) in RA-FLS which were stimulated by IL-17A was decreased slowly (t=4.22,P＜0.05 and t=4.95,P＜0.01 and t=7.47,P＜0.01).Conclusion IL-25 can inhibit the stimulation of IL-17A on ERK1/2 and MMP-3 fractionally,which implies that it may take part in the development of RA through this pathway and may be a target for the RA treatment.