Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Objective:To compare the early and mid-term results of hybrid coronary revascularization (HCR) and minimally invasive multivessel coronary artery bypass grafting (MICS-CABG) in coronary artery disease patients with low left ventricular ejection fraction and non diabetes mellitus, and to explore the indication of HCR and MICS-CABG.Methods:A retrospective cohort analysis of HCR and MICS-CABG cases with preoperative left ventricular ejection fraction less than 0.40, and without diabetes mellitus were conducted in Xijing Hospital from January 2015 to December 2019. 36 cases in HCR group and 17 cases in MICS group were included in this study. For HCR procedure, minimally invasive left internal mammary artery(LIMA) to the left anterior descending artery (LAD) bypass surgery were performed, and followed by percutaneous coronary intervention (PCI) to treat non LAD lesion 1 to 4 weeks later. MICS-CABG procedure was performed through left anterior small thoracotomy minimally invasive direct coronary artery bypass grafting for multiple diseased vessels.Results:The preoperative SYNTAX score in MICS group was significantly higher than that in HCR group ( P<0.05). There was no perioperative death in both groups. Troponin I, postoperative drainage volume, blood transfusion volume and ventilator ventilation time in MICS group were significantly higher than those in HCR group ( P<0.05). After 12 months follow-up, no patient died in both groups. Furthermore, all LIMA grafts were patency. The stenosis rate of drug-eluting stents in HCR group was similar to that of great saphenous vein grafts in MICS group. LVEF and left ventricular end diastolic diameter of both groups were significantly improved 12 months after operation ( P<0.05). Conclusion:HCR and MICS-CABG are minimally invasive and safe treatment for multivessel coronary artery disease patients with low ejection fraction and non diabetese mellitus. The early and mid-term therapeutic effects are satisfactory. If coronary artery lesions other than LAD are suitable for PCI, HCR should be the preferred treatment.

Objective    To investigate the therapeutic effect, safety and effectiveness of multiple valvular surgery through right anterolateral intercostal thoracotomy, as well as the mid-term follow-up results and surgeon's learning curve. Methods    The clinical data of 154 patients with multiple valvular disease were performed minimally invasive cardiac surgery in the Department of Cardiovascular Surgery, The First Affiliated Hospital of Air Force Medical University, from 2015 to 2019 were retrospectively analyzed. There were 103 males and 51 females, aged 23-68 years. Closed cardiopulmonary bypass was established through femoral artery and femoral vein, and the thoracic cavity was entered through a 6 cm transverse incision in the fourth intercostal space on the right side of sternum. Baseline and perioperative characteristics and postoperative outcomes were reviewed. Results    There was no perioperative death. The average cardiopulmonary bypass time was 159.3±39.4 min, and the aortic clamping time was 102.3±20.3 min. One patient underwent thoracotomy during the operation, and two patients underwent second thoracotomy for hemostasis. During the follow-up period of 10-55 months, 1 patient died, 2 patients developed mild perivalvular regurgitation, 6 patients developed moderate tricuspid regurgitation, and no serious cardiovascular events occurred in the rest of the patients. Conclusion    Our findings demonstrate that multiple valvular surgery through right anterolateral intercostal thoracotomy is safe, and in an acceptable risk of complication. The early and middle follow-up results are satisfactory. The minimally invasive cardiac surgery can also meet the requirements of cosmetology, and is conducive to the recovery of patients' mental and physical health. This method is worthy of application in medical centers with rich experience in routine cardiac surgery.

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective To investigate the influence factors of mortality among human immunodeficiency virus (HIV)-infected children under highly active antiretroviral therapy (HAART).Methods Retrospective cohort study of 652 children initiated HAART from 2005 to 2014 was conducted,and enrolled patients were followed-up until December,2015.Survival data was analyzed using Kaplan-Meier method and Cox regression model was used to identify independent predictors of mortality among these children on HARRT.Chi-square test and Fisher's exact test were used for comparison between groups.Results Overall,26 of the children died over a follow-up period of 3 116.24 child-years,with a mortality rate of 0.83 per 100 child-years.Twelve (46％)of deaths occurred during the first six months after starting HAART.Cox regression analysis of variables showed that the World Health Organization (WHO) clinical stages Ⅲ/Ⅳ (hazard rate [HR] =10.717,95％confidence interal [95％ CI]:4.189-4.749,P =0.000),baseline hemoglobin ＜ 80 g/L (HR =14.768,95 ％ CI:5.721-38.125,P =0.000),tuberculosis co-infection (HR =4.794,95％ CI:2.105-10.918,P =0.000),baseline CD4+T lymphocyte ＜ 50 cells/μL (HR =4.219,95％ CI:1.524-11.680,P =0.006),weight-for-age z-score ＜-2 (HR =2.983,95 ％ CI:1.094-8.135,P =0.033) were independently associated with death,whereas the age ＜ 7 year-old at HAART initiation was protectire (HR =0.293,95％ CI:0.126-0.684,P =0.005).Conclusions The mortality of children receiving HAART is strongly associated with WHO stages Ⅲ/Ⅳ,hemoglobin ＜ 80 g/L,weight-for-age z-score ＜-2,tuberculosis co-infection and older age at treatment.

A 68?year?old female patient was admitted to the hospital for multiple masses in the mouth and lungs as well as on dorsal hands for more than 20 days without obvious subjective symptoms. No abnormalities were found by physical examination. Dermatological examination showed two bean?sized dark?red nodules on the upper jaw as well as one pigeon egg?sized dark?red nodule on the left dorsal hand, and all the nodules were hard with smooth surfaces and limited mobility. Positron emission tomography?computed tomography (PetCT) revealed multiple metastases to the brain, lymph nodes, lungs, gastrointestinal tract, both kidneys, multiple bones and intermuscular tissues. Pathology of nodules from the upper jaw showed lowly differentiated tumor cells with osteoid matrix, chondroid structures and tumor bone in local areas, and immunohistochemical examination of tumor cells found positive staining for S100(focally), vimentin, CD99, P63 and Ki?67(60%), but negative staining for keratin. A diagnosis of osteosarcoma of the right side of the upper jaw was considered. Pathology of nodules from the dorsal hand revealed no obvious abnormalities in the epidermis, while there was a diffuse infiltration of medium?to large?sized histiocyte?like cells in the whole dermis with cell atypia and irregularly red?stained bone matrix and tumor bone in some regions. Immunopathology showed positive staining for Ki67(60%), and negative staining for CD3, CD10, CD20, Bcl?2, and Bcl?6. A diagnosis of cutaneous metastasis of osteosarcoma was made. The patient refused further treatment and died 6 months after the onset of lesions.

Objective To evaluate the current clinical application of domestic tirofiban in patients with acute coronary syndrome (ACS) and to explore its safety profile focused on the common causes and correlation factors for the hemorrhagic events.Methods The patients diagnosed as ST-elevation myocardial infarction (STEMI) and medium to high risk non-ST-elevation myocardial infarction (NSTEMI)/ unstable angina(UA) in 15 hospitals from September 2009 to December 2011 and given domestic tirofiban,were enrolled in this study.The following data were carefully collected:demographic data,comorbidities,concomitant medications,laboratory data,interventional treatment,application of tirofiban,hemorrhagic events and major adverse cardiac events(MACE) in hospital and at day 30 after discharge.Results (1) A total of 927 patients were enrolled in the study.The domestic tirofiban was given to 241 subjects (26.0％) before the intervention,567 subjects (61.2％) during the intervention and 89 subjects (9.6％) after the intervention.The standardized application was performed in 737 subjects (79.5％) with the loading dose of 10 μg/kg and the maintenance dose of 0.15 μg · kg-1 · min-1 In all the subjects,the average maintenance time was (30.4 ± 14.2) hours with the average dose of (339.3 ± 182.9)ml.(2)During hospitalization,major bleeding happened in 4 cases(0.4％) and major adverse cardiac events (MACE) in 37 cases (4.0％).(3)At day 30 after discharge,1 cases (0.1％)was reported with major bleeding and 9 cases (1.0％) with MACE.(3)The least MACE was showed in the preoperative tirofiban group (2.5％) and followed by the intraoperative group (4.1％) and the postopcrative group (9.0％).Compared with the non-standardized application group,MACE was significantly decreased in the standardized application group (2.44％ vs 10.00％,P ＜ 0.05).Conclusions The standardized application of the domestic tirofiban could decrease the incidence of MACE.Taken into account the combination therapy of clopidogrel and aspirin in the vast majority of patients,the domestic tirofiban exhibits a good safety profile with a relatively lower incidence of bleeding than the similar clinical studies.

BACKGROUND: Skidproof wrist protection devices can well protect the waist.OBJECTIVE: To analyze the efficacy of wrist protectors against fracture using three-dimensional finite element analysis.METHODS: Based on original data of Mechanical Virtual Human of China, three-dimensional finite element models of wrist with normal soft tissues and wrist wearing protectors were established using Abaqus6.51 software. The model was subjected to loading of 2 m/s. Stress-strain distribution of finite element model of the wrist before and after protectors wearing was compared, and maximum stress variation with time in the distal ulna was analyzed.RESULTS AND CONCLUSION: Compared with wrist not wearing protectors, the equivalent stress at soft tissues of hypothenar eminence, dorsal wrist, inferior segment of the radioulna, and distal radioulna was significantly decreased, which the stress at the second and fourth metacarpal bone, proximal segment of the index finger, and hamate bone was significantly increased, indicating the wrist protector can disperse, or transfer some stress from the distal radius and ulna to the wrist, palm or digital bone, thereby playing a positive role in preventing dital radial and ulnar fractures.