Objective To evaluate the process risk of the implementation of prevention and control measures for surgical site infection(SSI)after colorectal surgery,and explore the application effect of failure mode and effects analysis(FMEA)based on action priority.Methods FMEA based on action priority was adopted to evaluate the whole process of the implementation of prevention and control measures for SSI after colorectal surgery.Prioritiza-tion ranking was conducted according to whether optimized measures were taken.Standard-reaching rate of comp-liance to SSI prevention and control measures as well as SSI incidence before and after the implementation of FMEA were compared.Results After evaluation,there were 7 high-priority and 22 medium-priority prevention and control measures for SSI.The control of medium-priority measures was strengthened,with a focus on developing further preventive and detectable measures for high-priority measures.The re-evaluation results after improvement showed that 7 high-priority measures have been downgraded to medium priority,and 16 medium-priority measures have been downgraded to low priority.Standard-reaching rate of compliance to SSI prevention and control measures in-creased from 77.15％(2 566/3 326)to 92.47％(3 096/3 348),and SSI incidence decreased from 6.04％(58/960)to 2.54％(60/2 364).Conclusion Application of FMEA based on action priority can effectively evaluate the risk of prevention and control process of SSI after colorectal surgery,and adopting preventive risk control measures accord-ing to the current situation can reduce the incidence of SSI after colorectal surgery.

Aim To investigate the mechanisms of Chaijin JieYu Anshen formula modulating the depres-sive behaviors and the synaptic plasticity of hippocam-pal neurons in insomnia-concomitant depression rats based on the histone deacetylase 5(HDAC5)/myocyte enhancer factor 2C(MEF2C)pathway.Methods A rat model of insomnia-concomitant depression was es-tablished by PCPA injection combined with chronic un-predictable mild stress(CUMS),and the experiment was divided into the control group,the model group,the high,medium and low dose group of Chaijin JieYu Anshen formula,and the positive drug group.The de-pression of rats was evaluated by sugar-water prefer-ence test,open field test and morris water maze.The levels of 5-hydroxytryptamine(5-HT)and dopamine(DA)in serum were measured by enzyme linked im-munosorbent assay(ELISA).The pathological damage of hippocampal neurons was observed by HE staining and Nissl staining.The damage of dendritic spines of hippocampal neurons was observed by Golgi staining,and the levels of HDAC5,MEF2C,postsynaptic densi-ty-95(PSD-95)and synaptophysin 1(SYN1)in hip-pocampus were measured by Western blot,immunohis-tochemistry and immunofluorescence.Results Com-pared with the model group,the Chaijin JieYu Anshen formula could increase the sugar-water preference rate of the model rats,reduce the immobility time in the open field experiment,increase the total activity dis-tance,shorten the evasion latency in the localization navigation experiment,and prolong the residence time in the quadrant where the platform was located in the space exploration experiment(P＜0.05,P＜0.01).Moreover,the Chaijin JieYu Anshen formula improved the hippocampal neuron and dendritic spine damage and increase the dendritic branch length and dendritic spine density of hippocampal neurons(P＜0.01,P＜0.01),restore the serum levels of 5-HT and DA in insomnia-concomitant depression rats(P＜0.05,P＜0.01),down-regulate the HDAC5 protein,and up-regulate the expression of MEF2C,PSD-95,and SYN1 protein(P＜0.05,P＜0.01 or P＜0.001).Conclusions Chaijin JieYu Anshen formula may alle-viate the depression-like behavior of model rats by re-ducing the expression of HDAC5 protein,thus deregu-lating the inhibition of transcription factor MEF2C,promoting the expression of PSD-95 and SNY1 protein,and exerting a protective effect on hippocampal neurons and synapses.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Objective To investigate a new mode of training for emergency residents by WeChat,case-based learning (CBL) and team-based learning (TBL).Methods From January to December of 2017,a total of 160 emergency residents with bachelor degree in Beijing Chao-Yang Hospital,whose training time were more than 4 months,were involved in this investigation.Residents in treatment group (n=80) received the training with WeChat,CBL and TBL.In the control group (n=80),the residents received the traditional training protocols.At the end of training,the final examination and satisfactory inquire were done to evaluate the outcomes of treatment.Results The final examination scores of the control and treatment group was 66.4±6.0 and 71.7±4.4 respectively,significant difference was found between the two groups (t=4.012,P=0.012).The satisfactory inquire evaluation of the control and treatment group was 72.5±7.1 and 80.2±3.7,significant difference was found between the two groups too (t=4.764,P=0.001).Conclusions The new training method of WeChat with CBL and TBL can improve the teaching and the satisfactory degree of the emergency residents significantly.

Objective To assess the effect of isosorbide dinitrate on the improvement of cardiac function after cardiopulmonary resuscitation (CPR) by regulating myocardial cells apoptosis..Methods Total of 30 domestic pigs were divided into three groups randomly (random mumber) after anesthetization:the sham group (n=6),the control group (n=12),and the isosorbide dinitrate group (n=12).Cardiac arrest of ventricular fibrillation was induced by programed electrical stimulation in the control and isosorbide dinitrate groups.Isosorbide dinitrate was infused at the rate of 2 μg/(kg·min) in the isosorbide dinitrate group.Coronary perfusion pressure (CPP) and cardiac output (CO) were recorded at baseline,2,6,12 and 24 h after restoration of spontaneous circulation (ROSC).Myocardial enzyme and heart fatty acid binding protein (H-FABP) was tested at the same time points.At 24 h after ROSC,the animals were sacrificed to obtain the myocardium for pathological section and Western blot.The expression of Bcl-2,Bax and activated Caspase-3 were tested and apoptosis was tested by TUNEL and apoptosis index was calculated.Results Right atrial pressure (RAP) increased after ROSC and decreased in the isosorbide dinitrate group compared with the control group (P＜0.05).CPP at 12,24 h after ROSC and CO at 24 h after ROSC in the isosorbide dinitrate group increased significantly compared with the control group (both P＜0.05).HE staining revealed that the injury of myocardial cells was ameliorated in the isosorbide dinitrate group.Apoptosis index of the isosorbide dinitrate group significantly decreased than the control group [(37.8±15.5)％ vs (13.1±0.5)％,P＜0.05].The expression of Bax and activated Caspase-3 decreased while Bcl-2 and Bcl-2/Bax increased after ROSC in the isosorbide dinitrate group compared with the control group (all P＜0.05).Conclusions Isosorbide dinitrate could improve the isehemia/reperfusion injury and cardiac function after ROSC by inhibiting apoptosis regulated with Caspase-3 pathway.

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.
Cord Blood Stem Cell Transplantation ; Core Binding Factor Alpha 2 Subunit ; Graft vs Host Disease ; Humans ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; Oncogene Proteins, Fusion ; Peripheral Blood Stem Cell Transplantation ; RUNX1 Translocation Partner 1 Protein ; Transplantation Conditioning

The mechanism for icaritin to improve postmenopausal osteoporosis (PMOP) has not been clarified. The aim of this study was to investigate the role of estrogen receptor α36 (ERα36) in the proliferation promotion and anti-apoptosis effects of icaritin on osteoblasts and the underlying mechanism of downstream signal transduction. The ERα36 knockdown human osteosarcoma MG63 cell model was constructed by transfection of shRNA vector. Cell proliferation was detected by CCK-8, the apoptosis was detected by flow cytometry, and the activation of ERK and AKT signaling pathways was detected by Western blot. The results showed that the effects of icaritin on the proliferation and apoptosis of MG63 cells were significantly decreased after ERα36 knockdown, and icaritin could up-regulate the levels of ERK and AKT phosphorylation in MG63 cells, which could be reduced by ERα36 knockdown. The effect of icaritin on the proliferation of MG63 cells was significantly decreased by pretreating the cells with U0126 (an ERK signaling pathway blocker) and LY294002 (an AKT signaling pathway blocker), respectively. Furthermore, anti-apoptotic effect of icaritin on MG63 cells was significantly decreased after the cells were pretreated with U0126, but not with LY294002. These results suggest that icaritin exerts proliferation promotion and anti-apoptosis effects on osteoblasts through ERα36 and its downstream ERK and AKT signaling pathways.

Objective To explore the therapeutic efficacy of levofloxacin combined with anti-tuberculosis drugs and thoracic catheterization for the treatment of tuberculous pleuritis.Methods Patients who were admitted to Departments of Infectious Diseases of Hanzhong Central Hospital and Ankang Central Hospital between February 2014 and August 2016 for initial treatment of tuberculous pleuritis were included in the study,they were divided into groups A,B,C and D.Group A received 2HRZE + 7HR regimen combined with conventional drainage;group B received 2HRZE+ 7HR regimen combined with thoracic catheterization;group C received 2HRZEV + 7HR regimen combined with thoracic catheterization;group D received 2HRZEV + 10HR regimen combined with thoracic catheterization.groups B,C and D received thoracic catheterization,normal saline 20mL and urokinase 100,000U were given through the drainage tube.Results A total of 172 patients with newly diagnosed tuberctlous pleurisy were received for treatment.There were 45,53,38,and 36 cases in group A,B,C,and D respectively.The total effective rate of therapy for pleural effusion in group A was lower than that in group B(64.44％ vs 90.57％,x2 =9.863,P＜ 0.05);after two month therapy,total effective rate of therapy for pleural effusion in group B was lower than that in group C (18.87％ vs 39.47％,x2 =4.716,P＜0.05);at the end of therapy,total effective rate in group C was lower than that in group D (60.53 ％ vs 83.33 ％,x2 =4.731,P＜0.05).Conclusion For initial treatment of patients with tuberculous pleuritis,2HRZEV + 10HR antituberculosis regimen combined with thoracic catheterization and urokinase infusion can significantly improve the clinical symptoms and recovery rate of tuberculous pleuritis,facilitate drainage of pleural effusion and prevent pleural thickening,adhesion and encapsulation.

BACKGROUND:Internal and external fixation combined with autologous bone graft for treating atrophic nonunion has a long treatment cycle,and moreover,it cannot achieve a 100％ cure rate.Platelet-rich plasma contains a variety of growth factors and a large number of white blood cells,and contributes to tissue healing.However,there is no clinical study on the effectiveness of platelet-rich plasma combined with conventional surgery in the treatment of atrophic nonunion.OBJECTIVE:To investigate the effectiveness of platelet-rich plasma in the treatment of atrophic nonunion of femoral shaft fractures.METHODS:We conducted a prospective,open-label,randomized,controlled clinical trial at the Affiliated Hospital of Qinghai University,China.Ninety-two patients with atrophic nonunion of femoral shaft fractures were equally and randomly divided into control group and experimental group.Patients in the control group received conventional surgery.Patients in the experimental group were injected with autologous platelet-rich plasma on the basis of conventional surgery.The primary outcome was fracture healing rate at postoperative 9 months.The secondary outcomes were visual analogue scale scores in resting state and during passive motion,healing time,treatment costs,and adverse reactions.The study protocol was approved by the Ethics Committee of Affiliated Hospital of Qinghai University of China (approval number:QHG0223A) on May 20,2014.Written informed consent was provided by each patient and their family members after they fully understood the treatment plan.RESULTS AND CONCLUSION:Our partial results demonstrated that visual analogue scale scores and complications were similar between the two groups at postoperative 1-3 days.The healing rate was significantly higher in the experimental group than in the control group.The healing time was significantly shorter in the experimental group than in the control group.This trial will provide objective data for the clinical use of platelet-rich plasma combined with conventional surgery for the treatment of atrophic nonunion.