OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Based on high-resolution magnetic resonance tube wall imaging,reverse medical engineering modeling techniques are used to obtain individualized intracranial artery models of high prevalence in ischemic stroke.Three types of intracranial artery models,including Newtonian fluid model,non-Newtonian fluid model and non-Newtonian fluid with two-phase flow model,are established for transient numerical simulations using computational fluid dynamics method.The hemodynamic parameters such as blood flow field,wall shear stress distribution and erythrocyte volume distribution are analyzed to investigate the possible mechanisms involved in the formation and progression of intracranial atherosclerosis.It is found that blood flow velocity increased significantly at the end of the internal carotid artery and the middle cerebral artery.Low-speed vortex flow and disturbed flow appear in the local vessels.The difference in blood flow velocity between the center and the edge of the wall is large,with an obvious low-flow velocity area on the outer side.A clear central core area is formed in the stenotic wall under the action of high-speed blood flow,resulting in thinner edge layer and lower erythrocyte volume fraction.The combination of low erythrocyte distribution in the edge layer and low flow velocity on the outer side of the wall exacerbates endothelial cell necrosis,hypoxia,endothelial dysfunction,and leads to atherosclerosis.Compared with Newtonian and non-Newtonian fluid models,non-Newtonian fluid with two-phase flow model has greater variability for hemodynamic parameters and shows higher fidelity in simulating blood flow,which provides a reference for clinical diagnosis and treatment of cerebrovascular diseases.

Objective To investigate the efficacy and safety of bivalirudin versus unfractionated heparin during perioperative primary percutaneous coronary intervention(PCI)in elderly patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 423 elderly patients with acute STEMI who underwent primary PCI in our hospital were consecutively en-rolled in this study.According to different perioperative anticoagulant regimens,they were divided into bivalirudin group(187 cases)and unfractionated heparin group(236 cases).Baseline data,characteristics of interventional procedures and complications during hospitalization were ana-lyzed.Primary endpoint was major adverse cardiac or cerebral events(MACCE).Secondary end-points were net adverse clinical events.Other observational indicators included stent thrombosis,acquired thrombocytopenia,BARC types 1-2 bleeding and total bleeding events.Results In-hospital MACCE and all-cause mortality were significantly lower in the bivalirudin group than unfractionated heparin group(3.7％vs 9.7％,P=0.021;3.7％vs 8.9％,P=0.039).Univariate logistic regression analysis showed that perioperative application of bivalirudin significantly reduced all-cause mortality in the patients with Killip grade Ⅰ and creatinine clearance ≥60 ml/min when compared with unfractionated heparin(P＜0.05).Conclusion In elderly patients with acute STEMI,perioperative use of bivalirudin significantly reduces the incidences of MACCE and all-cause death during hospitalization,especially in the patients with Killip grade Ⅰ and creatinine clearance ≥60 ml/min.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To discuss the oncologic safety, aesthetic outcome, and upper extremity function of single-port insufflation endoscopic nipple-sparing mastectomy (SIE-NSM) in the treatment of early breast cancer.Methods:From January 2014 to August 2019, a total of 80 patients with stage Ⅰ and Ⅱ breast cancer underwent SIE-NSM, at Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed and followed up. Estimated the oncologic safety, aesthetic outcome, and upper extremity function.Results:SIE-NSM was performed successfully on all 80 patients.There was no serious complication after surgery.The follow-up time was 16-82 months and the median follow-up time was 42 months. Local recurrence occurred in two patients, and there was no distant metastases. Four (5%) patients developed grade 1-3 nipple-areola complex ischemia. There were no cases of subcutaneous effusion.The satisfaction with breasts, chest well-being, psychosocial well-being, and sexual well-being scores were confirmed to be highly rated by Breast-Q scale. Upper extremity function score confirmed that good upper limb function was preserved after surgery. The mean length of incision was (3.6±0.8) cm, and the blood loss was (24.7±19.3) mL.Conclusions:SIE-NSM can achieve a higher cosmetic score and a better recovery of upper limb function on the premise of ensuring the safety of the tumor.This novel method is an appropriate surgical option for patients with early breast cancer.

Objective:To examine the clinical application value of single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation in the treatment of early breast cancer.Methods:From February 2014 to July 2019, the clinic-pathological data of 34 early breast cancer patients received single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation at Department of General Surgery, Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed and followed up. All the patients were female, with an age of 46(11) years ( M( Q R)) (range: 26 to 64 years). The radical cure degree of operation, cosmetic effect after operation were evaluated. The satisfaction to operation and personal quality of life after operation was accessed by BREAST-Q scale. Results:All surgical procedures were successfully completed. The operation time was (313.4±11.7) minutes (range: 200 to 485 minutes). The blooding-liquid was (33.8±3.3) ml (range: 10 to 100 ml). There were 5 cases (14.7%) of nipple areola necrosis after operation, of which 1 patient received taking the prosthesis out because of prosthesis exposure. There was no capsular contracture or postoperative bleeding case. The follow-up time was 35(17) months (range: 12 to 77 months), and there was one case suffering local recurrence and metastasis, and another suffering metastasis. The scores of postoperative breast satisfaction, psychosocial status, chest wall status and sexual health were 78.32±2.57 (range: 55 to 100), 89.12±2.30 (range: 82 to 100), 91.47±1.33 (range: 43 to 100), and 78.50±2.68 (range: 39 to 100).Conclusion:Single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation in the treatment of early breast cancer can achieve provided curative and cosmetic effect on patients with breast cancer, with good patients′ postoperative quality of life and satisfaction.

Objective:To examine the clinical application value of single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation in the treatment of early breast cancer.Methods:From February 2014 to July 2019, the clinic-pathological data of 34 early breast cancer patients received single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation at Department of General Surgery, Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed and followed up. All the patients were female, with an age of 46(11) years ( M( Q R)) (range: 26 to 64 years). The radical cure degree of operation, cosmetic effect after operation were evaluated. The satisfaction to operation and personal quality of life after operation was accessed by BREAST-Q scale. Results:All surgical procedures were successfully completed. The operation time was (313.4±11.7) minutes (range: 200 to 485 minutes). The blooding-liquid was (33.8±3.3) ml (range: 10 to 100 ml). There were 5 cases (14.7%) of nipple areola necrosis after operation, of which 1 patient received taking the prosthesis out because of prosthesis exposure. There was no capsular contracture or postoperative bleeding case. The follow-up time was 35(17) months (range: 12 to 77 months), and there was one case suffering local recurrence and metastasis, and another suffering metastasis. The scores of postoperative breast satisfaction, psychosocial status, chest wall status and sexual health were 78.32±2.57 (range: 55 to 100), 89.12±2.30 (range: 82 to 100), 91.47±1.33 (range: 43 to 100), and 78.50±2.68 (range: 39 to 100).Conclusion:Single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation in the treatment of early breast cancer can achieve provided curative and cosmetic effect on patients with breast cancer, with good patients′ postoperative quality of life and satisfaction.

Objective: To explore the application effect of fine needle aspiration cytology and sentinel lymph nodes stain assisted by contrast-enhanced ultrasound in early breast cancer. Methods: A patient with early breast cancer enrolled in Beijing Friendship Hospital, Capital Medical University received fine needle aspiration cytology assisted by contrast-enhanced ultrasonography and the sentinel lymph nodes were stained with blue dye before a standard sentinel lymph nodes biopsy traced with indocyanine green. The axillary status accessed by these two methods were compared. Results: Three sentinel lymph nodes were found and aspirated assisted by contrast-enhanced ultrasonography. Seven sentinel lymph nodes were obtained in sentinel lymph nodes biopsy surgery. All of these sentinel lymph nodes were negative. The stained sentinel lymph nodes could be recognized and dissected in open lymph nodes biopsy surgery. Conclusions Fine needle aspiration cytology assisted by contrast-enhanced ultrasonography could be a substitute for open sentinel lymph nodes biopsy. More related researches should be carry out to further compare these two methods.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance and genetic susceptibility and is one of the chronic liver diseases that threaten human health .Under certain conditions, Th17 cells and regulatory T (Treg) cells can be transformed to each other to maintain immune homeostasis.In recent years, more and more studies have been performed on the involvement of Th 17 and Treg cells in the development and progression of liver diseases .Th17 cells, Treg cells, and their balance may become the new targets for the treatment of NAFLD.This article reviews the latest research advances in the association of Th 17 and Treg cells with NAFLD and the role of Th17/Treg balance in the development and progression of NAFLD .

Objective To investigate the application value of pH sensitive manganese-loaded caramelized carbonaceous nanospheres (Mn-CNS) in the synchronous MRI and photothermal therapy for breast cancer. Methods Anhydrous glucose was used as carbon source to prepare caramelized carbonaceous nanospheres(CNS).Mn2 +was absorbed and bonded to its surface to obtain the Mn-CNS.The MR signal values of aqueous solutions of Mn-CNS under different pH(pH=7.4,6.0,5.0)with different Mn2+concentrations(0,0.14,0.28,0.57,1.14 and 2.28 mmol/L)were measured to obtain the relaxation rate.The cell counting kit-8(CCK-8)assay was used to determine the effect of Mn-CNS on the viability of 4T1 cells. Pathological examination was used to evaluate the systemic toxicity. Inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze Mn uptake by different cell lines (human breast cancer cells MCF-7, human normal mammary epithelial cells MCF-10A and human macrophages cells). The 4T1 tumor-bearing BALB/c mice were divided randomly into four groups (6 mice per group): (1) normal saline (intratumoral injection)plus near infrared laser(NIR);(2)normal saline(intravenous injection)plus NIR;(3) Mn-CNS(intratumoral injection)plus NIR;(4)Mn-CNS(intravenous injection)plus NIR.After intratumoral injection for 30 min and intravenous injection for 12 h,the tumors were continuously irradiated with 808 nm laser for 10 min,the temperature changes and relative tumor volume were recorded.The MRI was obtained at different time point(pre-injection and post-injection at 15 min,30 min,1 h,4 h,8 h,12 h,24 h,48 h,4 d, respectively)with the dose of Mn-CNS(4 mg Mn/kg)by intravenous injection.The changes of Mn2+content before and after Mn-CNS incubation and the tumor volume differences among each group were compared by t test.Results The values of r1were 0.18 L·mmol-1·s-1(pH 5.0),3.48 L·mmol-1·s-1(pH 6.0)and 5.42 L· mmol- 1·s- 1(pH 7.4), respectively. The cells viability of 4T1 were all above 90 % when the cells were incubated with Mn-CNS at different concentrations (25, 50, 100 and 200 μg/ml). MCF-7 and human macrophages cells were ingested Mn2+.The Mn2+amount before and after uptake were significant difference(P<0.05).The MCF-10A had a slight uptake of Mn2+which was not statistically significant(P>0.05).After 10 minutes of the laser exposure (2 w/cm2), the change of temperature with tumor among different groups were shown as follow:Mn-CNS(intratumoral injection)>Mn-CNS(intravenous injection)>normal saline(intravenous injection)>normal saline (intratumoral injection). After photothermal therapy, the relative tumor volumes of Mn-CNS (intratumoral injection)and normal saline(intratumoral injection)were statistically different(t=-2.724,P<0.05). Meanwhile,the relative tumor volumes also showsd significant difference among Mn-CNS(intravenous injection) and normal saline (inject intravenous injection) groups (t=-5.193,P<0.05). After intravenous injection of Mn-CNS in 4T1 tumor-bearing mice, the signal intensity of T1gradually increased and reached the peak of enhancement at 4 h after which the signal intensity remained stable and decreased slightly at 12 h,then gradually decreased to normal. The T1signal intensity of kidney was consistent with that of the tumor and higher. Meanwhile, the degree of liver tissue enhancement was the lowest. Conclusions Mn-CNS is highly biocompatible and self-degradable,it can targeted MRI and achieve precise photothermal therapy simultaneously, which is of great value in the integrated diagnosis and treatment of breast cancer.