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Thromboembolic diseases are major health problems worldwide,and remain the leading cause of mortality and disabil-ity at present.Bleeding is the most important complication of an-tithrombotic therapy for thromboembolism,therefore research and development of new antithrombotic drugs with lowered bleeding risk is a significant medical need.The data that elevated plasma levels of FXI are associated with thromboembolic diseases,se-vere FXI deficiency reduced incidence of DVT and ischemic stroke,and FXI deficiency or inhibition in animals shows protec-tive effects against thrombus formation supporting FXI as a novel antithrombotic target with lowered bleeding risk.This paper re-views the progress on FXI as a novel antithrombotic target and the inhibitors target FXI.

Objective:To evaluate the impact of laparotomy pancreatoduodenectomy (OPD), laparoscopic pancreatoduodenectomy (LPD) and Da Vinci robot assisted pancreatoduodenectomy (RPD) on the risk of pancreatic fistula in postoperative patients.Methods:The key words were laparoscopic, pancreaticoduodenectomy, robot, DaVinci, Whipple, complication, fistula, pancreaticoduodenectomy, laparoscopy, robot, postoperative complications and pancreatic fistula, and the databases of CNKI, Wanfang, VIP, CBM, Cochrane Library, PubMed, EMBASE and web of science were searched until August 1, 2020 for retrospective cohort studies and randomized controlled trials comparing the efficacy of OPD, LPD and RPD. The articles were screened according to the pre-set inclusion and exclusion criteria, and the quality of the articles was evaluated and the data were extracted. Based on Bayesian framework, R4.0.2, Revman 5.3 and Stata 16.0 software were used to analyze the extracted data for mesh meta analysis.Results:Thirty articles involving 3 428 patients were included, including 26 retrospective cohort studies and 4 randomized controlled studies. Mesh meta-analysis showed that in the incidence of pancreatic fistula, there was no significant difference between LPD and OPD, between LPD and RPD ( OR=0.93, 95% CI 0.63-1.4; OR=1.4, 95% CI 0.87-2.2, P<0.05), but the incidence of postoperative pancreatic fistula was significantly lower than that of OPD ( OR=1.5, 95% CI 1.1-2.1, P<0.05), 95% CI 1.12.1; P>0.05). The risk probability of pancreatic fistula was ranked as RPD (0.00), LPD(0.34) and OPD(0.65), that is, for the risk of postoperative pancreatic fistula, the advantages and disadvantages of the three surgical methods were ranked as RPD, LPD and OPD. Conclusions:Compared with OPD, RPD can significantly reduce the risk of pancreatic fistula after PD and improve the quality of operation; there was no significant difference between LPD and RPD in the incidence of postoperative pancreatic fistula, and both of them were safe and feasible.

Background Interleukin-6 (IL-6) is a pleiotropic cytokine involving in inflammation and wound healing.Previous report found that IL-6 increases phosphorylated STAT3 (p-STAT3) level and promotes corneal epithelial wound healing by stimulating migration.However,the essential role of IL-6 in corneal epithelial wound healing and the expression changes in diabetic mellitus remains unknown.Objective This study was to explore the roles of IL-6 in corneal epithelial proliferation and wound healing in both normal and diabetic mice.Methods Fifty-two normal C57BL/6 mice were randomized into normal control group (32 mice) and diabetic group (20 mice).Type 1 diabetic mellitus was induced by intraperitoneal injections of 50 mg/kg streptozotocin once per day for consecutive 5 days in the mice of the diabetic group.Whole corneal epithelium was scraped in all mice,and the corneal epithelial defect area was examined by fluorescein staining in 24,48 and 72 hours after corneal epithelium removal.Recombinant mouse IL-6 or anti-IL-6 blocking antibody of 5 μl were subconjunctivally injected according to the grouping and contrasted with PBS injection group or isotype control antibody group,respectively.TKE2 cells,a mouse corneal epithelial stem/progenitor cell line,were trypsinized and incubated in the KSFM with different concentrations of IL-6 or without IL-6,and colony formation efficency (CFE) was examined by crystal violet staining.The expressions of △NP63 and Ki67,specific makers of stem cells,were detected by immunofluorescine technology.The expressions of △NP63,Ki67 and p-STAT3 proteins were assayed in the cells by Western blot,respectively.The expression of IL-6 mRNA and protein in the regenerated corneal epithelium was detected by real time quantitative PCR and ELISA.The use and care of the mice complied with the Statement of Association for Research in Vision and Ophthalmology.Results The percentage of residual corneal epithelium defect area with initial detect area was gradually shrinked over time after PBS and IL-6 injection in both normal control mice and diabetic mice,and the percentage of residual corneal epithelium defect area was significantly reduced in the IL-6 injected group compared with the PBS injected group (normal control group:Fgroup =19.982,P ＜ 0.01;Ftime =589.350,P ＜ 0.01;Diabetic group:Fgroup =25.411,P＜0.01;Ftime =334.807,P＜0.01).The CFE was (13.23± 1.12)％,(15.87± 1.30)％,(21.69±1.62)％,(25.33±1.28)％ and (18.67±1.54)％ in the blank control group and 10,20,50,100 ng/ml IL-6-treated groups,respectively,showing a gradual increase of CFE dependent upon IL-6 concetrations (F =35.547,P＜0.01).The expressions of △NP63,Ki67,p-STAT3 proteins in the cells were gradually increased over time after 50 ng/ml IL-6 treated for 5,10,15,30 and 60 minutes,and the relative expression level of the cytokines was significnatly higher in the IL-6 cultured groups than that without IL-6 culture group (all at P＜0.05).The relative expression of IL-6 mRNA in the regenerated corneal epithelilum was 0.45±0.21 and 1.00±0.16 in the diabetic group and normal control group,respectively,and compared with the normal control group,the expression of IL-6 mRNA reduced by 56％ (t=3.42,P=0.03).The content of IL-6 protein in regenerated corneal epithelium of the diabetic group was (257±12) ng/μl,which was significantly lower than (323 ± 17) ng/μl of the normal control group (t =5.60,P＜0.01).Conclusions IL-6 promotes the proliferation and regeneration of corneal limbal stem cells to repair defected corneal epithelium by activating STAT3 signaling pathway in both normal and diabetic mice,while the blocking of endogenous IL-6 impairs the corneal epithelial cell activation and wound healing.

Objective:To compare the clinical efficacy of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) in the treatment of infants with severe respiratory syncytial virus (RSV) pneumonia.Methods:A prospective randomized controlled trial was conducted. The infants with severe RSV pneumonia who received invasive mechanical ventilation admitted to intensive care unit (ICU) of Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2018 to December 2019 were enrolled. According to the order of admission, each infant was assigned to HFOV group or CMV group by random number table. The basic data, pediatric critical score, blood gas analysis, ventilator parameters, oxygenation index [OI, OI = mean airway pressure (Pmean)×fraction of inspired oxygen (FiO 2)/arterial partial pressure of oxygen (PaO 2)×100], duration of mechanical ventilation, length of ICU stay, complications, prognosis, use of muscle relaxants and vasoactive drugs and other clinical indicators of the two groups were recorded. Results:A total of 28 infants were enrolled in the analysis, including 15 infants receiving CMV and 13 infants receiving HFOV. There were no significant differences in age, body weight, pediatric critical score and OI before enrollment, type Ⅱ respiratory failure, multiple organ dysfunction, basic diseases and laboratory examination indexes before enrollment between the two groups. Six hours after enrollment, compared with CMV group, heart rate (HR), respiratory rate (RR), case of transcutaneous oxygen saturation (SpO 2) decrease, case of HR decrease, case of cardiopulmonary resuscitation (CPR) and OI in HFOV group were significantly decreased [HR (bpm): 130 (125, 138) vs. 144 (140, 160), RR (times/min): 35 (34, 38) vs. 40 (35, 45), SpO 2 decrease (case: 1 vs. 10), HR decrease (case: 0 vs. 6), CPR (case: 0 vs. 4), OI: 6.5 (4.4, 8.9) vs. 9.3 (8.0, 12.8)], while case of use of muscle relaxants (case: 3 vs. 0) and volume of 7-day positive fluid balance [mL/kg: 167.1 (113.8, 212.6) vs. 90.8 (57.8, 112.7)] were significantly higher, the differences were statistically significant (all P < 0.05). There was no use of blood purification treatment, no severe complications such as pneumothorax and intracranial hemorrhage, and no death within 28 days in the two groups. Conclusion:Compared with CMV, HFOV in the treatment of infants with severe RSV pneumonia can improve the oxygenation level and clinical physiological indexes earlier, reduce the incidence of adverse events such as HR, SpO 2 decrease and CPR, increase the use of muscle relaxants and the positive fluid balance, and do not increase the incidence of severe complications such as pneumothorax and intracranial hemorrhage, so its clinical application is safe.

Objective To study the effect and safety of modified Valdivia position and prone position in percutaneous nephrolithotomy(PCNL) on renal calculi.Methods The clinical data of 94 patients with solitary renal calculi admitted in our hospital from September 2015 to November 2016 were enrolled to this study,who were divided into control group and study group by surgery methods and body position,47 cases in each group.The control group received PCNL with prone position,and the study group were treated by PCNL with modified Valdivia position.The operative condition,postoperative condition,stone clearance rate and incidence of adverse reactions between the two groups between two groups were compared,and the levels of diastolic blood pressure(DBP),systolic blood pressure(SBP) and heart rate(HR) between the two groups were observed.Results After position placement,DBP and SBP level decreased in both groups,the level of DBP and SBP in study group were lower than the control group,the difference was significant(P<0.01).There was no significant difference in the level of HR between two groups(P>0.05).The operative time,intraoperative blood loss,hospitalization time,reoperation rate and blood transfusion rate in the study group were lower than those in control group,the differences were significant(P<0.05),the removal rate of stones was significantly higher than that of control group(χ2=9.55,P=0.00).The rate of chest stuffy and dysphoria in the study group were higher than those in control group(P<0.05).The incidence of infection,hemorrhage,pleural injury and renal injury were slightly lower than those of the control group,but there was no significant difference between two groups(P>0.05).Conclusion PCNL with modified Valdivia position has high safety and significant effect on patients with kidney stones,which can effectively remove stones,reduce operation time.

Objective To investigate the impact of 1,25(OH)2D3 on histological changes and activation of STAT3 in BLM?induced pulmonary fibrosis mice. Methods 30 male C57BL/6 mice were randomly divided into control group ,BLM group and BLM+VD group. Mice in BLM group and BLM+VD group received intratracheal injection of BLM(3 U/kg). Control group were intratracheally injected equal volume of sterile saline. From the first day after the surgery,mice in BLM+VD group received intraperitoneal injection of VD (5μg/kg·d). After 21 days, H&E and Masson′s trichrome staining were carried out. Aschroft score were used to evaluate histological changes in lungs. IL?6,IL?4 and INF?γin BALF were assessed by Elisa. p?STAT3,α?SMA and Collagen I were detected by western blot (WB) and immunohistochemistry. Results Fibrosis score and level of α?SMA,Collagen I in BLM group were significantly higher than that in control group (P < 0.05). However ,treatment with VD effectively at?tenuated fibrosis (P<0.05). IL?6 and IL?4 increased while INF?γwas decreased in BALF of BLM group (P<0.05). VD could ameliorate these changes. Upregulation and neuclear translocation of p?STAT3 were observed in BLM group,while VD intervention could inhibit phosphorylation of STAT3. Conclusions VD attenuate BLM?induced pulmonary fibrosis and regulate inflammatory cytokines probably by blocking STAT3 activation.

Objective To explore the role of MKK34 (a peptide spanning a C-terminal α-helical region in TSLP) on airway inflammation and β-catenin of airway epithelium in a HDM-induced mouse asthma.Methods 32 male BALB/c mice were randomly divided into control,MKK34,asthma and MKK34 + HDM groups.The mice in the asthma group were exposed to HDM for five consecutive days and the MKK34 + HDM group was pretreated with MKK34 1 h prior to the HDM intranasally treated.After 8 weeks' treatment,animal lung function test and pathological staining were performed to evaluate the asthma situation,IL-4,IFN-γin bronchoalveolar lavage fluid and IgE in the serum were detected,immunohistochemistry and western blot were used to assess β-catenin and p-ERK,t-ERK levels.Results Airway reactivity,IL-4 and IgE in the asthma group were significantly higher than that in the control group.Treatment with MKK34 significantly decreased airway hyperresponsiveness,IL-4 and IgE.HE staining demonstrated the chronic bronchitic inflammation in the lungs of asthma group.β-catenin in the control group was distributed evenly at the cytomembrane of epithelial cells.In the asthma group,β-catenin was disordered in epithelial cells and its expression was decreased.Treatment with MKK34 ameliorated the damage of β-catenin and chronic bronchitic inflammation.The protein levels of p-ERK1/2 increased obviously in the asthma group.The pretreated group significantly decreased the expression of p-ERK1/2.Conclusions MKK34 can ameliorate the airway inflammation and the destruction of β-catenin of airway epithelium in a HDM-induced mouse asthma.The ERK pathway may play a role in this process.

Tyrosyl-DNA phosphodiesterase Ⅰ (TdpⅠ ) is a recently discovered proteinthat catalyzes the hydrolysis of 3′-phosphotyrosyl bonds .Such linkages form in vivo during the interaction of DNA and topoisomerase Ⅰ (TopⅠ) .TdpⅠ has been regarded as a potential therapeutic co-target of TopⅠ because it has the functions of repairing Top Ⅰ compound and coun-teracting the effects of Top Ⅰ inhibitors .TdpⅠ inhibitors can not only synergizing with Top Ⅰ-targeting drugs (camptoth-ecins) ,but also strength the function of bleomycin ,topoisomerase Ⅱ (TopⅡ ) inhibitors (etoposide ,doxorubicin) and DNA alkylating agents .We summarized the researching advance of TdpⅠ inhibitors and focused on the introduction of the mecha-nism ,bioactivity and structure-activity relationship .

Objective To determine the results of treatment combining all-trans-retinoic acid(ATRA)in childhood acute promyelocytic leukemia(APL).Methods 22 children with newly diagnosed APL received induction therapy with ATRA followed by 3 courses of consolidation chemotherapy:daunorubicin,idarubicin,homoharringtonine or aclacinomycin plus cytosine arabinoside.A maintenance therapy was then administered with ATRA and these reigems for 36 months.Results Early deaths from diffuse intravazcular clotting and intracranial hemorrhage occurred in two patients.The other children achieved a complete remission(CR).By June 2007,the estimated disease-free survival rates at 1,3 and 5 years were 100%,93.3% and 84.7%;respectively.The side effects of ATRA were xerosis eutis and xerocheilia,headaches,nausea and vomiting,hepatic function lesion and ATRA syndrome.Conclusion Remission induction therapy with ATRA is effective and safe for newly diagnosed childhood APL.The maintenance therapy combined chemotherapy with ATRA can improve the long-term effects of APL patients.The main causes of death in APL children is diffuse intravascular clotting and intracranial hemorrhage.The side effects of ATRA can be tolerated.