Immune thrombocytopenia (ITP) is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury. ITP has complicated immunopathological mechanisms that need further elucidation. It is well known that the costimulatory molecules OX40 ligand (OX40L) and OX40 play essential roles in the immunological mechanisms of autoimmune diseases. Previously, we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells (PBMCs) of ITP patients. In our present study, OX40L-induced follicular helper T (Tfh) cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PD-1), and cluster of differentiation 40 ligand (CD40L) in vitro. Moreover, aberrant OX40L‒OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo, inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model, which might accelerate the progression of ITP. Additionally, signal transduction through the OX40L‒OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor (TRAF)‒nuclear factor-κB (NF-κB) and Janus kinase (JAK)‒signal transducer and activator of transcription (STAT) signaling pathways. Overall, OX40L‒OX40 signaling is proposed as a potential novel therapeutic target for ITP.
Animals ; OX40 Ligand/physiology* ; Purpura, Thrombocytopenic, Idiopathic/immunology* ; Cell Differentiation ; Mice ; T-Lymphocytes, Helper-Inducer/cytology* ; T Follicular Helper Cells/cytology* ; Signal Transduction ; Receptors, OX40 ; Mice, Inbred C57BL ; Humans ; Female

Radiotherapy is an effective way to reduce the local recurrence rate and mortality of breast cancer.However,the risk of long-term side effects of radiation-induced cardiac injury cannot be ignored.Especially for patients undergoing left breast ra-diation therapy,the risk of cardiac injury is higher due to the heart being within the radiation field,which increases the incidence of radiation induced heart disease and ultimately affects long-term survival rate and quality of life.Therefore,it is particularly important to prevent radiation induced cardiac injury.The main measures include using advanced radiation therapy techniques such as intensity modulated radiation therapy,volume modulated arc radiotherapy,deep inhalation and breath holding radiation therapy,prone position radiation therapy,proton beam therapy,etc.or optimizing the radiotherapy plan for cardiac substructure to reduce the radiation dose to key cardiac structures.This article will review the research progress of pathophysiological mechanism,clinical manifestations,risk fac-tors and preventive measures of radiation-induced cardiac injury in breast cancer.

Objective:To evaluate the efficacy and safety of endoscopic ultrasound (EUS)-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt.Methods:Data of 24 patients with gastric fundal varices with large spontaneous shunt (the smallest diameter was 5-15 mm) treated by EUS-guided coil embolization combined with endoscopic cyanoacrylate injection in Renmin Hospital of Wuhan University from December 2016 to December 2020 were retrospectively analyzed. The short-term efficacy (the rates of technical success, five-day rebleeding and six-week mortality) and long-term efficacy (the rates of one-year rebleeding, one-year mortality and three-year mortality) and safety (ectopic embolism) were evaluated.Results:The technical success rate was 91.7% (22/24), and the five-day rebleeding rate was 0 (0/22). Computed tomography angiography of portal vein reexamined 2 days after the treatment showed embolism of splenic vein in 1 patient (4.5%). The median follow-up time was 14.9 months (ranging 1.0-48.6 months) and 2 patients were lost during follow-up. The six-week mortality was 0 (0/20), and the one-year rebleeding rate was 35.0% (7/20). Among 12 patients who underwent endoscopy in the follow-up, 5 had aggravation of esophageal varices, and 5 had aggravation of portal hypertension gastropathy. The one-year and three-year mortalities were 5.0% (1/20) and 20.0% (4/20), respectively, neither of which was related to such events as bleeding or ectopic embolism.Conclusion:EUS-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt is effective and safe in short term, with a low rate of ectopic embolism. Long-term efficacy and safety need to be further confirmed.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

OBJECTIVE：To provide reference for the c onstruction of subject diagnosis and treatment scheme in drug clinical trials. METHODS ：The subject diagnosis and treatment module was developed and implemented in our hospital on the basis of CTMS，and its effects were evaluated. RESULTS ：A subject diagnosis and treatment module was established in CTMS of our hospital. Within one year from the launch of the module in the middle of October ，2019，the overall number of subjects in the group showed an increasing trend ，and the overall mean dropout rate of subjects was 0.16％. The data interface of CTMS system ， hospital information system （HIS），laboratory information management system ，medical imaging information system had been established，so as to realize the synchronization of subject information （displaying subject identification in HIS system ）and the interaction of diagnosis and treatment information and billing data （patients and subjects were charged separately ）. Since the launch of the module ，the amount of data generated by the interface had been increasing ，and the number of departments producing the subject diagnosis and treatment business had been increasing month by month. Compared with subject diagnosis and treatment project based on HIS system ，the number of subject diagnosis and treatment business based on CTMS system was increased significantly（P＜0.05）. CONCLUSIONS ：The subject diagnosis and treatment module based on CTMS improves the efficiency of subject diagnosis and treatment project implementation and financial settlement ，and realizes the efficient implementation of drug clinical trial projects in large general hospitals.

Objective:To evaluate the efficacy and safety of lactulose combined with polyethylene glycol for bowel preparation before colonoscopy in patients of different risks.Methods:A total of 208 patients undergoing colonoscopy were enrolled, including 108 high-risk and 100 low-risk patients. The high-risk patients were divided into group A (54 taking lactulose + polyethylene glycol) and group B (54 taking polyethylene glycol), and the low-risk patients were divided into group C (49 taking lactulose + polyethylene glycol) and group D (51 taking polyethylene glycol). The Boston bowel preparation score, cecal intubation time, withdrawal time, the detection rate of colonic polyps and adenoma, and the incidence of adverse reactions were observed.Results:Among the high-risk patients, the Boston bowel preparation score and adenoma detection rate in group A [(6.35±1.15) scores, 46.3%] were significantly higher than those in group B [(5.76±0.89) scores, 22.2%, both P<0.05], and the first defecation interval in group A was significantly shorter than that in group B [(1.20±0.85) h VS (3.29 ± 2.93) h, P<0.05]. There was no significant difference in adequate bowel preparation rate, polyp detection rate, frequency of defecation or incidence of adverse reactions between group A and B. In the low-risk patients, the first defecation interval in group C was significantly shorter than that in group D [(1.65 ± 1.35) h VS (3.42 ± 2.64) h, P<0.05], and the incidence of adverse reactions was significantly lower than that in group D (44.9% VS 64.7%, P<0.05). There was no significant difference in adequate bowel preparation rate, Boston bowel preparation score, adenoma detection rate, polyp detection rate or frequency of defecation between group C and D. Conclusion:For the high-risk patients, the effect of lactulose combined with polyethylene glycol for bowel cleansing is better than that of traditional polyethylene glycol in the improvement of the Boston bowel preparation score, adenoma detection rate, and the first defecation interval. For low-risk patients, lactulose combined with polyethylene glycol regimen has few advantages over traditional polyethylene glycol regimen.

Objective:To establish an air-pouch bladder cancer (APBCa) model and investigate whether it could be a new animal model to evaluate the efficacy of intravesical therapy through chemotherapeutics and BCG instillation.Methods:Filtered sterile air was injected subcutaneously into the backs of BALB/c Nude mice to create a 2.5 cm×3.5 cm air pouch. After 24 hours, human bladder cancer cells EJ were seeded on the inner face of the pouch wall to establish APBCa of human cancer (H-APBCa). Gemcitabine instillation was used to investigate whether chemotherapy could inhibit tumor growth in the H-APBCa model, and Tunel staining was used to verify the apoptosis of tumor cells 20-day treatment. Filtered sterile air was injected subcutaneously into the backs of C57BL/6 mice to create a 2.5 cm×3.5 cm air pouch. After 24 hours, mice bladder cancer cells MB49 were seeded on the inner face of the pouch wall to establish APBCa with intact immunity (I-APBCa). BCG instillation was used to investigate whether BCG could inhibit tumor growth in the APBCa model. Immunofluorescence was used to verify the infiltration of immune cells after 20-day treatment.Results:H-APBCa and I-APBCa mice models could be established by immune deficiency and intact mice. At day 20, chemotherapeutic instillation therapy could inhibit tumor growth (781.02±241.02 vs. 1213.88±214.02 mm 3, P<0.05) by inducing tumor cell apoptosis with statistically significant differences (77.33±4.63 vs. 14.67±2.60, P<0.05). BCG instillation was able to inhibit tumor growth (645.02±156.63 vs. 948.84±221.76, P<0.05) by increasing CD80 + macrophage (49.67±7.57 vs. 16.33±5.69, P<0.05) and T cells in the tumor with statistically significant differences (18.00±3.46 vs. 4.67±1.45, P<0.05). Conclusions:APBCa model could evaluate the efficacy of drug instillation and was expected to be a new animal model for studying drug for intravesical therapy.

Objective The aim of this study was to investigate the dosimetric advantages of Gating in the treatment of prima-ry hepatic cancer with large segmentation. Methods A retrospective analysis of 10 patients with primary liver cancer from August 2017 to November 2018 after interventional therapy was performed using three consecutive phases of end-tidal phase to achieve pa-tient-controlled large-segment radiotherapy. Ten patients underwent 4DCT localization scan,and 10 respiratory phase sequences were reconstructed by respiratory wave-form,and the images were transmitted to the MIM6. 7. 6 workstation. In the MIM workstation, full-time phase maximum density projection(MIP-10),full-time phase average density projection(Mean-10),end-expiration 3 phase maximum density projection(MIP-3) and end-expiration 3 phase average density projection( Mean-3) were generated re-spectively,where MIP was used for target delineation and Mean for dose calculation. The radiotherapy doctor delineated IGTV-10 and IGTV-3 on the MIM workstation,and released CTV-10,CTV-3,PTV-10 and PTV-3 to compare the volume differences of the target area. After the target area was drawn,the image was transmitted from the MIM workstation to the Eclipse treatment planning sys-tem,and the full-time phase plan(Plan-10)with the same conditions and three consecutive phase-phase gating plans(Plan-3) were prepared. The prescriptive dosage was given at 50 Gy/10 f/2weeks. Comparing the HI and CI of the target area,the comparison of organs at risk included: the average dose of liver Dmean,the irradiation volume of liver less than 15Gy,the Dmax of small intestine, the Dmax of colon, the Dmax of stomach, the average dose of the kidney Dmean, the heart Dmax, and the spinal cord Dmax. Results The volume of the target area delineated at the end of expiratory phase was less than that of the target area outlined by the full-time phase in IGTV,CTV and PTV,and the difference was statistically significant(P<0. 05). In the two groups of seven field coplanar lage-segment radiotherapy plans,the 3-phase respiratory gating plan significantly reduced the dose of the organs at risk, and the difference was statistically significant(P<0. 05). At the same time,there was no statistically difference in the HI and CI be-tween of the two groups(P>0. 05). Conclusion The gated target area delineation and planning design of the three consecutive pha-ses of end-tidal phase reduce the volume of IGTV,CTV and PTV target regions compared with the selection of full-time phase,and have obvious advantages in the planned dosimetry. The irradiation dose that threatens the organs is worthy of being promoted and ap-plied in the large-scale radiotherapy of liver cancer.

Objective To explore the effect of tea polyphenols on the growth of human papillomavirus 16 (HPV16) subgenes-immortalized human cervical epithelial cells (H8 cells).Methods Cultured H8 cells were divided into 5 groups to be treated with 0 (control group),6.25,12.5,25 and 50 mg/L tea polyphenols respectively for 24,36,and 48 hours,and then cell counting kit-8 (CCK8)assay was performed to detect cell proliferation.After 24 hours of incubation,flow cytometry was conducted to detect cell apoptosis and cell cycle,and fluorescence microscopy to observe the morphology of apoptotic cells.Results After incubation with tea polyphenols at different concentrations for 24,36 and 48 hours,the proliferation of H8 cells was inhibited,and 12.5 mg/L tea polyphenols could inhibit the relative growth rate of H8 cells in a time-dependent manner.Flow cytometry showed that there was a significant difference in cell apoptosis rate among the 6.25-,12.5-,25-,50-mg/L tea polyphenols groups and the control group (52.62％ ± 0.62％,52.22％ ± 0.72％,42.52％ ± 0.90％,45.96％ ± 2.11％,29.96％ ± 0.70％ respectively,F =272.0,P ＜ 0.05).Moreover,all the tea polyphenol groups showed significantly increased cell apoptosis rate compared with the control group (all P ＜ 0.05).Fluorescence microscopy showed karyopyknosis,nuclear fragmentation and other typical apoptotic morphological changes in H8 cells in tea polyphenols groups.There were significant differences in the percentage of cells in G1,G2 phase and cell proliferation index among the 5 groups (all P ＜ 0.05).Compared with the control group,the 6.25-,12.5-,25-mg/L tea polyphenols groups showed significantly increased percentage of cells in G1 phase (55.96％ ± 0.72％,54.12％ ± 3.20％,65.30％ ± 1.51％ respectively,all P ＜ 0.05),but significantly decreased percentage of cells in G2 phase (3.17 ± 1.82％,4.94 ± 1.46％,4.65 ± 4.26％ respectively,all P ＜ 0.05) and lower cell proliferation index(0.44 ± 0.01,0.46 ± 0.02,0.36 ± 0.01 respectively,all P ＜ 0.05).Conclusion Tea polyphenols can inhibit the proliferation of H8 cells,induce cell apoptosis,and block cell cycle progression.

OBJECTIVE:To investigate the possible mechanism of Artemisia capillaries,and to provide reference for further development and utilization of it. METHODS:The effective components and related target protein of A. capillaries were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) analysis platform database. The effective compound-target protein visual network of A. capillaries was established by using Cytoscape 3.5.1 software,topology analysis was also performed. The protein-protein interaction (PPI) network was constructed and analyzed by STRING database. KEGG pathway enrichment of target protein coding gene was analyzed by DAVID bioinformatics resource database. RESULTS:A total of 13 kinds of effective compounds,189 target proteins and 34 enrichment pathways were selected. Quercetin,β-glutamol,isorhamnetin and artepillin C were main effective compounds. Prostaglandin G/H sythase 2(PTGS 2),heat shock protein 90(HSP 90),dipeptidyl peptidase Ⅳ, protein kinase A catalytic subunit Cα were main target proteins. Transcription factor AP-1 and cell tumor antigen p53 played a key role in PPI network. The target protein coding gene was rich in TNF-α signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,PI3K/Akt signaling pathway,T cell receptor signaling pathway,thyroid hormone signaling pathway, apoptotic signaling pathway,etc. CONCLUSIONS:Quercetin,β-glutamol and isorhamnetin of A. capillaries play an effect on PTGS2,HSP90,transcription factor AP-1 and other target proteins through TNF-α signaling pathway,HIF-1 signaling pathway and PI3K/Akt signaling pathway,so as to play anti-inflammatory and antitumor effect.