Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Objective:To summarize the efficacy of general anesthesia for percutaneous pulmonary valve implantation (PPVI).Methods:The clinical data of 6 patients underwent PPVI under general anesthesia in Children′s Heart Center of Henan Provincial People′s Hospital from December 2017 to January 2020 were retrospectively analyzed.Systolic blood pressure, diastolic blood pressure, heart rate, central venous pressure, SpO 2 and regional cerebral oxygen saturation were recorded before anesthesia induction (T 1), after anesthesia induction (T 2), before beginning of surgery (T 3), before pulmonary valve implantation (T 4), during pulmonary valve implantation (T 5), immediately after pulmonary valve implantation (T 6) and when the patients left the operating room (T 7). Right ventricular systolic pressure, diastolic pressure, pulmonary artery systolic pressure and diastolic pressure were recorded at T 4 and T 6.The development of related complications during operation and the cardiac, liver and kidney functions before and after operation were recorded.The postoperative extubation time, intensive care unit stay time and hospital stay time were recorded. Results:Six patients (3 males, 3 females), aged (16±4) yr, weighing (41±12) kg, were analyzed.Compared with the value at T 1-4 and T 6, 7, systolic blood pressure, diastolic blood pressure, heart rate, regional cerebral oxygen saturation and SpO 2 were significantly decreased at T 5 ( P<0.05). Compared with the value at T 1-5, central venous pressure was significantly decreased at T 6, 7 ( P<0.05). Compared with the value at T 4, right ventricular diastolic pressure was significantly decreased, and pulmonary artery diastolic pressure was increased at T 6 ( P<0.05). No anesthesia- and surgery-related serious complications occurred among the patients.One patient was transferred to the ward after extubation in the operating room, and 5 patients were transferred to the intensive care unit after operation.All 6 patients were discharged successfully and entered the follow-up stage. Conclusion:General anesthesia provides better efficacy when used for PPVI, and hemodynamic monitoring of pulmonary circulation and systemic circulation should be strengthened during pulmonary valve implantation to maintain circulation stable.

Objective:To compare the application effect of blue dye single tracer and blue dye combined with nuclide double tracer in sentinel lymph node biopsy (SLNB) of breast cancer surgery.Methods:A total of 92 breast cancer patients in Shandong Cancer Hospital and Institute from November 2017 to October 2019 underwent methyleneblue dye combined with 99Tc m sulfur colloid nuclide double tracer in SLNB, while other 92 cases in Jining First People Hospital underwent blue dye single tracer. The number of SLN detection, detection rate, accuracy rate, sensitivity, and false negative rate of the two groups were compared. The impacts of age, menstruation, tumor location, tumor size, clinical stage, pathological type, and estrogen receptor (ER), progesterone receptor (PR), human epidermal receptor 2 (HER-2), molecular typing, dynamic enhanced magnetic resonance imaging (DCE-MRI)on the detection rate of SLN were analyzed. Results:The number of detection, detection rate, accuracy, sensitivity, and false negative rate of the blue dye single tracer group were 3.20±1.10, 90.22%, 93.48%, 95.24% and 4.76%, respectively; the double tracer group were 3.37±1.02, 92.39%, 95.65%, 95.65% and 4.35%, respectively, without significant difference (all P>0.05). In different age, menstrual condition, tumor location, clinical stage, pathological type, ER, PR, HER-2 expression and molecular typing, the detection rate of single tracer group and double tracer group had no significant difference (all P>0.05). However, in the tumor size of 2-5 cm and without DCE-MRI examination, the detection rate of single tracer group was significantly lower than that of double tracer group. Conclusion:The effect of blue dye single tracer in detecting SLN of breast cancer is equivalent to that of double tracer method, which is worthy of promotion and application in primary hospitals.

Objective:To compare the application effect of blue dye single tracer and blue dye combined with nuclide double tracer in sentinel lymph node biopsy (SLNB) of breast cancer surgery.Methods:A total of 92 breast cancer patients in Shandong Cancer Hospital and Institute from November 2017 to October 2019 underwent methyleneblue dye combined with 99Tc m sulfur colloid nuclide double tracer in SLNB, while other 92 cases in Jining First People Hospital underwent blue dye single tracer. The number of SLN detection, detection rate, accuracy rate, sensitivity, and false negative rate of the two groups were compared. The impacts of age, menstruation, tumor location, tumor size, clinical stage, pathological type, and estrogen receptor (ER), progesterone receptor (PR), human epidermal receptor 2 (HER-2), molecular typing, dynamic enhanced magnetic resonance imaging (DCE-MRI)on the detection rate of SLN were analyzed. Results:The number of detection, detection rate, accuracy, sensitivity, and false negative rate of the blue dye single tracer group were 3.20±1.10, 90.22%, 93.48%, 95.24% and 4.76%, respectively; the double tracer group were 3.37±1.02, 92.39%, 95.65%, 95.65% and 4.35%, respectively, without significant difference (all P>0.05). In different age, menstrual condition, tumor location, clinical stage, pathological type, ER, PR, HER-2 expression and molecular typing, the detection rate of single tracer group and double tracer group had no significant difference (all P>0.05). However, in the tumor size of 2-5 cm and without DCE-MRI examination, the detection rate of single tracer group was significantly lower than that of double tracer group. Conclusion:The effect of blue dye single tracer in detecting SLN of breast cancer is equivalent to that of double tracer method, which is worthy of promotion and application in primary hospitals.

Objective To investigate the clinical features and risk factors of multidrug－resistant bacteria (multi drug resistant organisms, MDROs) infection in Department of Neurosurgery, and to provide evidence for the prevention and control of MDRO infection. Methods Data from 437 cases of infection in hospitalized patients on January 2012－2016 year in December Third Affiliated Hospital of Guizhou Medical University were retrospectively analyzed. Patients were divided into MDROs group and non MDROs group based on the results of MDROs detection. Multi factor Logistic regression analysis model was used to analyze risk factors. Results The infection rate of MDROs was 35.51%, and the detection rate of MDROs was 33.23% . ESBLs, CR－AB and MRSA were the most common bacterial species, and the infection of respiratory tract, urinary tract and wound infection were the main infection sites. Multivariate logistic regression analysis showed that hospitalization time ＞20 d, level of consciousness (coma), occupancy of ICU ≥7 d, ventilation (invasive), number of antibiotics used≥3, combined use of antibiotics≥3, mechanical ventilation Time≥7 d were possible risk factors for MDROs infection in neurosurgical patients (P＜0.05). Conclusion The situation of MDROs infection in neurosurgery is severe. To reduce MDROs infection, it is important to shorten unnecessary hospitalization time, promptly assess and transfer out of ICU as soon as possible, improve microbial examination, avoid frequent change of antibiotics or unnecessary use of use of broad－spectrum antibiotics, reduce unnecessary mechanical ventilation time, change to non－invasive ventilation as far as possible when the condition permits, focus on patients with poor consciousness, and prevent aspiration by mistake.

Objective: To compare the clinicopathological characteristics of second primary lung cancer following breast cancer and lung metastases from breast cancer, and then to analyze the risk factors in breast cancer patients with second primary lung tumor. Methods: Clinical data of 55 breast cancer patients with second primary lung tumor and 205 breast cancer patients with solitary pulmonary metastasis in Shandong Cancer Hospital from January 2006 to January 2017 were retrospectively analyzed. The risk factors of primary lung cancer following breast cancer were analyzed using logistic regression model. Results: Second primary lung cancer in patients with first breast cancer accounted for approximately 21.2%(55/260) of pulmonary malignant solitary nodules, and 0.84%(55/6 580) of all breast cancer patients. The median intervals between the diagnosis of second primary lung cancer or lung metastasis and first breast cancer were 52 months and 42 months, respectively. These two groups showed significant difference between age, time interval between diagnoses, breast tumor size, axillary lymph node metastasis, estrogen receptor, molecular subtype (luminal B and triple-negative) and history of radiotherapy (P<0.05 for all). A multivariate logistic regression model confirmed that age (OR=1.088, P<0.001), breast tumor size(OR=0.480, P<0.001), and radiotherapy history (OR=3.460, P=0.004) were all independent factors for second primary lung cancer. Conclusions For isolated pulmonary nodules in patients with breast cancer, especially for those with elder age, larger tumor size and radiotherapy history, we should distinguish the second primary lung cancer from pulmonary metastasis. The treatment regimen for lung metastasis and primary lung cancer in patients with breast cancer are entirely distinct. The timely histopathology examinations for pulmonary nodes in patients with breast cancer are recommended.

BACKGROUND AND OBJECTIVES: The overall purpose of this study was to investigate the role of cytochrome C oxidase (CcO) in preventing ischemia reperfusion-induced cardiac injury through gaseous signaling molecule pathways. MATERIALS AND METHODS: We used CcO inhibitor, potassium cyanide (KCN) to mimic the pre-treatment of gaseous signaling molecules in a global ischemia/reperfusion (IR) injury model in rats. Intracellular reactive oxygen species (ROS) was determined by measuring mitochondrial H2O2 and mitochondrial complex activity. RESULTS: KCN pre-treatment led to decreased infarction area after IR injury and improved cardiac function. KCN pre-treated group challenged with IR injury was associated with reduced ROS production through inhibition of activity and not downregulation of CcO expression. In addition, KCN pre-treatment was associated with enhanced expression and activity of mitochondrial antioxidase, suggesting the role of CcO in regulating IR injury through oxidative stress. CONCLUSION: KCN pre-treatment reduced the severity of IR injury. The potential mechanism could be increased endogenous anti-oxidase activity and consequently, the enhanced clearance of ROS.
Animals ; Cytochromes c* ; Cytochromes* ; Down-Regulation ; Electron Transport Complex IV* ; Infarction ; Ischemia* ; Mitochondria ; Myocardial Infarction ; Oxidative Stress ; Potassium Cyanide ; Rats ; Reactive Oxygen Species ; Reperfusion Injury*

Objective To summarize the preliminary experience and early -stage follow -up results of simple transesophageal echocardiography(TEE)to guide right jugular internal vein for closure of atrial septal defect (ASD), and to investigate its feasibility.Methods A total of 24 ASD patients(12 male,12 female)treated by transcatheter ASD closure under solely guidance of TEE were summarized in Children Heart Center,People′s Hospital of Zhengzhou University from February 2015 to February 2016.Mean age,body weight and average diameter of the 24 cases of ASD were 5 -18 (12.4 ±5.6)years old,16 -60 (34.1 ±9.6)kg,5 -20 (11.0 ±2.5)mm,respectively.All patients were treated by right jugular internal vein transcatheter closure under solely guidance of TEE.The efficiency of imme-diate post -operation under TEE was estimated,and follow -ups were done at 24 hours,1 month,3,6 and 12 months after the procedures by transthoracic echocardiography,X -ray examination and electrocardiogram.Results A total of 23 patients were treated successfully under solely guidance of TEE.The diameter of devices was (14.5 ±3.6)mm.The procedural time was(20.5 ±7.2)min.One patient who had 2 ASD was treated by traditional thoracic surgery,because the small ASD had 5 mm residual shunt after the procedures.There were 3 cases with trivial residual shunt after the pro-cedures immediately.All patients could move at once after operation.The average follow -up time was(5.6 ±1.2) months.No patients suffered from residual shunt,occluder malposition,peripheral vascular injury,pericardial effusion or cardiac perforation during the follow -up.Conclusions For some selected patients,simple TEE guiding right jugular in-ternal vein for closure of ASD is applicable.The method not only prevents injury from radiation,but also shortens the in -bed time and avoid the lower limbs braking,with good early -stage follow -up results are desirable.

Objective: To explore the blood-saving effect of autologous platelet-rich plasma (PRP) back-transfusion in patients with Stanford type A aortic dissection surgery. Methods: A total of 59 consecutive patients who received Stanford type A aortic dissection surgery in our hospital from 2013-01 to 2015-10 were studied. The patients were at the age of (50±6) years with mean body weighting at (80±12) kg and were randomly divided into 2 groups: Traditional (T) group,n=31 and Autologous PRP back-transfusion (P) group,n=28. Blood levels of Hb, platelet counts, PT, APTT were measured at pre-induction of anesthesia (T1), before CPB (T2), prior ifnishing of CPB (T3) and at 1 h (T4), 24 h (T5), 48 h (T6) after the operation. The in-operative, 48 h post-operative volumes of allogeneic blood transfusion and the volume of chest tube drainage at 48h after operation were recorded; the complication occurrence at peri-operative period was recorded. Results: In P group, whole blood processing volume was (1269±197) ml, PRP volume was (753±78) ml, PRP separation time was (35±9) min and the separated platelets were about (22±3)% of total platelet counts. Compared with T group, P group had decreased Hb at T2 (131.0±15.0) g/L vs (101.0±10.0) g/L, decreased platelet counts at T3 (115.0±51.0)×109 /L vs (83.0±23.0)×109/L, while increased platelet counts at T4 (103.0±25.0)×109/L vs (151.0±27.0)×109/L, T5 (105.0±25.0)×109 /L vs (147.0±39.0)×109/L and T6 (101.0±26.0) ×109/L vs (149.0±35.0)×109/L, allP<0.05; P group presented reduced PT at T4 (17.6±2.1) s vs (14.1±1.1) s and T5 (17.6±2.7) s vs (13.5±0.8) s, allP<0.05. The in-operative transfusions of platelet, plasma, cold precipitation and post-operative transfusions of red blood cells, platelets, plasma, cold precipitation and the volume of chest tube drainage at 48h after operation were less in P group,P<0.05. Compared with T group, P group had the lower rates of acute post-operative lung injury (32.1% vs 19.4%), shorter mechanical ventilation time (69.1±5.9) h vs (43.1±1.5) h and ICU staying time (8.1±2.8) d vs (5.3±1.1) d, allP<0.05. Conclusion: Autologous PRP back-transfusion could reduce the post-operative bleeding and allogeneic blood transfusion for Stanford A aortic dissection surgery, it has obvious blood-saving effect.

Objective To investigate the effect of combined administration of autophagy inhibitor 3?methyladenine/bafilomycin A1 and EGFR inhibitor gefitinib on triple?negative breast cancer MDA?MB?468, MDA?MB?231 cells and estrogen receptor?positive MCF?7 cells. Methods All the cells were treated with 3?methyladenine/bafilomycin A1 and/or gefitinib. The effect of autophagy inhibitor and gefitinib on the cell growth was evaluated by MTT assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was used to determine the alteration of autophagy?related protein ( such as LC3) and apoptosis?related proteins ( such as caspase?3 and caspase?9) . Results MTT assay showed that the IC50 in the GE+3?MA and GE+BAF groups were (4.1±0.2) μmol/L and (3.8±0.3) μmol/L, significantly lower than that of the gefitinib alone group [(7.0±0.2) μmol/L] in MDA?MB?468 cells (P<0.05). Similarly, the IC50 in the GE+3?MA and GE+BAF groups were (9.7±0.1) μmol/L and (7.7±0.2) μmol/L, significantly lower than that of the gefitinib alone group [(14.7±0.1) μmol/L]in MDA?MB231 cells (P<0.05). The flow cytometry assay revealed that the apoptosis rates of MDA?MB?468 cells in GE, GE+3?MA and GE+BAF groups were (12.43± 3.18)%, (23.37±2.71)% and (18.71±2.81)%, respectively. The apoptosis rates of MDA?MB?231 cells of the GE, GE+3?MA and GE+BAF groups were (12.15±1.82)%, (16.94±2.19)% and (33.83±5.92) %, significantly higher than that of the gefitinib alone group (All P<0.05). The apoptosis rates of the MCF?7 cells were not changed significantly among the three groups (P>0.05). Western blot data showed that the expression levels of LC3 and p?Akt were decreased in the combined groups than that of the gefitinib alone group, while the p?PTEN, caspase?3 and caspase?9 were increased. Conclusions Autophagy inhibitor may enhance the sensitivity to gefitinib in MDA?MB?468 and MDA?MB?231 cells by activation of the PTEN/P13K/Akt pathway. Apoptosis in MDA?MB?468 and MDA?MB?231 cells might be enhanced by the combination treatment through caspase cascade.