In recent years,targeted drug delivery system as one of the hottest areas in pharmaceutical research has received more and more attention.However,the targeted anti-tumor drug delivery system has many shortcomings including low targeted efficiency which limit its clinical application.Elevating tumor targeting efficiency has become the bottleneck of nano-drug development and clinical application.Therefore,it is urgent to design and develop novel targeted drug delivery vehicle.Recent studies showed that mesenchymal stem cells (MSCs) have characters of tumor tropism and migration,which make them as ideal targeted anti-tumor drug delivery carriers for the treatment of solid and metastatic tumors.This paper reviews the progress in using MSCs as targeted anti-tumor drug delivery carrier,recapitulates the problems and challenges of the system,and proposes a solution for these problems.

Objective To investigate the appearance and characteristics of hepatic tuberculosis lesions on low mechanical index contrast-enhanced ultrasound. Methods Eight patients with hepatic tuberculosis lesions were studied with conventional ultrasound and contrast-enhanced ultrasound. Lesions,distribution.size,echogenieity,blood flow,enhancement phase,enhancement patterns and intensity were studied. ResuIts Fifteen lesions were found in eight patients. On conventional ultrasound,mean size of the lesions was(21.7±10.7)mm×(30.3±22.4)mm,and 66.7%(10/15)lesions located under liver capdule,and 33.3%(5/15)were in hepatic parenchyma.All lesions were hypoechoic except the largest one (50 mm x 102 mm)which demonstrated heterogeneous.Doppler signals were not demonstrated in all 15 lesions.After administration of SonoVue,satisfied image data were obtained in 13 lesions for aterial phase,and 15 lesions for portal venous phase and parenchyma phase.84.6%(11/13)of the lesions demonstrated hyperenhancing on aterial phase,mean enhancing start time was(8.6±1.6)s,ranging from 5 s to 10 s.and mean enhancing end time was(25.6±2.8)s,ranging from 20 s to 29 s. Of 13 lesions,6 lesions demonstrated circle periphery hyper-enchanCement,5 lesions demonstrated whole hyper-enchancement,and 2 lesions appeared hypoenhancement on arterial phase. All lesions demonstrated either hypoenhancing or non-enhancement on portal venous phase and parenchyma phase. Conclusions Low mechanical index contrast-enhanced ultrasound can reveal the blood flow status of hepatic tuberculous lesions and will facilitate the diagnosis of hepatic tuberculosis.

Objective To investigate the effects of Dihuangyinzi(DHYZ) on behaviors and RAGE/p38 pathway in APP/PS1 mice.MethodTwenty APP/PS1 dementia mice were randomly divided into model group(n=10) and Chinese medicine group(n=10).The blank group was C57 BL/6 J normal mouse(n=10).The mice in Chinese medicine group were intragastric administration with DHYZ (9.75 g·kg-1·d-1).The mice in model group and blank group were treated with distilled water.After 30 days,the abilities of learning and memory of mice were detected by Morris water maze.The expression of amyloid-beta1-42(Aβ1-42) in the hippocampus and cortex was detected by immunohistochemistry.Reactive oxygen species of brain tissue were detected by DCFH-DA Methods in the brain of APP/PS1 mice.Gene expression level of receptor for advanced glycation end products(RAGE) was measured by real-time polymerase chain reaction (RT-PCR) in the cortex and hippocampus of APP/PS1 mice.The expression of phospho-mitogen-activated protein kinases (p38) was analyzed with Western blot and immunofluorescence analysis in the cortex and hippocampus of APP/PS1 mice.Results Behavioral Results showed that DHYZ significantly increased the distance((23.088±7.083)cm) and residence time((1.961±1.230)s)of effective area in Morris water maze on the fifth day(P<0.05,P<0.01)and remarkably increased the number of effective area crossings((1.607±0.405) times) and plats((0.893±0.283) times) in Morris water maze on the fifth day(P<0.01,P<0.05).DHYZ also significantly reduced the intracelluar ROS level(122.611±7.630) in the brain(P<0.01),and DHYZ could depress the expression of RAGE(1.467±0.081,7.983±0.136) and phosphorylation of p38 (0.376±0.026,0.538±0.016)in the cortex and hippocampus of APP/PS1 mice(P<0.01,P<0.05).Conclusions The Results demonstrate that DHYZ can partly improve memory impairment of APP/PS1 mice by the inhibition of RAGE/p38 pathway.

Objective To investigate the effects of Dihuang Yinzi (DY) on the receptor for advanced glycation end-products(RAGE)/reactive oxygen species(ROS)/apoptosis pathway in SH-SY5Y cells induced by amyloid-beta1-42 (Aβ1-42) oligomer. Methods Firstly, we adopted methyl thiazolyl tetrazolium(MTT) method to detect the cell vitality in fetal bovine serum (FBS) group, blank serum group, and low-, middle- and high- dose DY-containing serum groups, so as to confirm the optimal concentration and treatment time of DY-containing serum. Secondly, we applied MTT method to detect cell vitality and applied Annexin V/propidium iodide (PI) staining method to observe the apoptosis of SH-SY5Y cells treated with 0~20 μmol/L Aβ1-42 for 24 and 48 h, so as toconfirm the optimal concentration and treatment time of Aβ1-42 for establishing Alzheimer's disease (AD) model in vitro. Thirdly, MTT method was used for the detection of cell vitality, and Annexin V/PI staining method was used for detection of the apoptosis of SH-SY5Y cells in blank serum group, model group, western medicine control group and low-, middle-and high-dose DY-containing serum groups, and Dihydroethidium (DHE) method was used for the assay of ROS contents, so as to observe the effect of DY on the recovery of injured SH-SY5Y cells induced by Aβ1-42. Finally, we applied Western blot method to detect the expression level of RAGE in SH-SY5Y cells of blank group, model group and DY-containing serum group; after Aβ1-42-induced SH-SY5Y cells were transfected with RAGE gene, we adopted DHE staining method and Annexin V/PI staining method to detect ROS content and cell apoptotic rate in all of the above groups, so as to observe the effect of DY on SH-SY5Y cell apoptosis and RAGE expression. Results The cell vitalities were increased in low- and middle-dose DY-containing serum groups at 24 h (P < 0.05 or P < 0.01 compared with that in the blank serum group). The conditions for the establishment of AD model in vitro were as follows: the optimal concentration of Aβ1-42 was 5μmol/L, and the treatment time was 24 h. The cell vitalities were significantly enhanced, the cell apoptotic rate and ROS content were significantly lowered in Aβ1-42-induced SH-SY5Y cells of the medication groups(P <0.05 or P < 0.01 compared with those in the model group) , and the cell vitality was the highest and the cell apoptotic rate was the lowest in the middle-dose DY-containing serum group. The RAGE expression level was decreased in Aβ1-42-induced SH-SY5Y cells of the middle-dose DY-containing serum group(P < 0.05 compared with that in the model group) . ROS content and cell apoptotic rate were decreased in Aβ1-42-induced SH-SY5Y cells transfected with RAGE gene in the middle-dose DY-containing serum group (P<0.01). Conclusion DY may play an anti-oxidative role through inhibiting the production of ROS and cell apoptosis, thus to suppress RAGE protein and to achieve the preventive and therapeutic effect for AD.

Objective To investigate the methods of early identification and early intervention for newborn with life-threatening congenital heart disease.Methods Between January 2010 and December 2010,223 neonates with serious congenital cardiac malformations were hospitalized in PICU of Fuwai Hospi-tal.Results The most type of cardiac lesions was complete transposition of the great arteries,accounting for 59%(131 cases),and the second was total anomalous pulmonary venous connection,17%(39 cases).For the primary clinical symptoms,the most common were any cyanosis,dyspnea and cardiac murmur,accounting for 91 %(204 cases),56%(125 cases)and 53%(1 18 cases),respectively.Fifty-nine cases developed into critical conditions such as severe hypoxia,metabolic acidosis and heart failure and were sent to PICU for emergency rescue.Early intervention included maintaining ductus arteriosus open,correcting internal environ-ment disturbances,treatment of heart failure,and surgical treatment as soon as possible.Four cases died before operation and 10 cases were abandoned to continue care,which all died within 12 days after discharge.In 209 cases who received operation,9 cases died.The total operation mortality was 4.3%.Within 3 to 63 month following-up,the late death was in 2 cases,2 cases received two-stage corrective operation,and three for reop-eration.The others all were in normal cardiac function and growth.Conclusion Most of neonatal life-threat-ening congenital cardiac malformations were ductus dependent such as transposition of the great arteries and total anomalous pulmonary venous connection,which the baby needs immediate diagnosis and management for survival.Early recognition,appropriate preoperative management and operation as soon as possible are the key to rescue.

Objective:To analyze the risk factors of postoperative recurrence of nonvalvular paroxysmal and persistent atrial fibrillation.Methods:A total of 100 patients who received treatment in Haining People's Hospital from October 2019 to October 2021 were included in this study. All patients were followed up for 1 year. Thirty patients with postoperative recurrence of atrial fibrillation were included in the observation group, and seventy patients without postoperative recurrence of atrial fibrillation were included in the control group. Univariate and multivariate logistic regression analyses were performed to analyze the risk factors of postoperative recurrence of atrial fibrillation after radiofrequency ablation.Results:Logistic regression analysis results revealed that age, body mass index, diabetes mellitus, hypertension, rheumatic heart disease, anteroposterior diameter of the left atrium, glycosylated hemoglobin, brain natriuretic peptide are the risk factors of recurrent atrial fibrillation after radiofrequency ablation (all P < 0.05) ( OR = 1.31, 1.33, 1.32, 1.34, 1.26, 1.24, 1.36, 1.33; 95% CI = 1.028-1.442, 1.031-1.427, 1.042-1.434, 1.124-1.452, 1.013-1.385, 1.005-1.326, 1.039-1.482, 1.064-1.478). Conclusion:The recurrence of nonvalvular paroxysmal and persistent atrial fibrillation after radiofrequency ablation is related to many factors. The risk factors should be taken into account in clinical practice, and targeted treatment should be given as early as possible to reduce the recurrence rate of atrial fibrillation and improve prognosis.

Objective To investigate the effect of schisandrin (SCH) treatment on learning and memory abilities and their mechanism in APP/PS1 dual transgenic dementia mice,and explore the effect of Chinese medicine on Alzheimer's disease (AD).Methods Thirty-five APP/PS1 dementia mouse models were randomly assigned into APP/PS1 model group (n=17) and APP/PS1+SCH group (n=18);another 10 male C57BL/6J mice were chosen as blank control group.The mice in the APP/PS1+SCH group were given intragastric administration of SCH at 2.6 mg/(kg· d) for 30 d;the mice in the APP/PS1 model group and blank control group were treated with distilled water for 30 d.The learning and memory abilities of these APP/PS1 mice (n=7) were detected by Morris water maze.Mice from the three groups were sacrificed;Nissl staining was used to observe Nissl bodies of neurons in brain tissues;real-time fluorescence quantitative PCR (qPCR) was used to detect the mRNA content of terminal glycosylationend products receptor (RAGE) in brain tissues;Western blotting was used to detect the expressions of RAGE and phosphorylated P38 mitogen-activated protein kinase (p-p38) in brain tissues.Results (1) The results of water maze space exploration experiment showed that the times of crossing the platform area in the three groups were statistically significant (P＜0.05);as compared with the APP/PS1 modelgroup,the times of crossing the platform area in the APP/PS1+SCH group were significantly increased (P＜0.05).(2) Nissl staining results showed that the contents of Nissl bodies in the hippocampal CA1 area and cortical neurons of the APP/PS 1 model group were significantly reduced,with light staining and cell body atrophy;the lesions in mice of the APP/PS1+SCH group were less severe than those of APP/PS1 model group,some neurons were atrophic,and the content of the neuronal nileite bodies in the hippocampal CA1 region was relatively abundant.(3) The qPCR results showed that there were statistically significant differences in RAGE mRNA expression levels in the cortex and hippocampus of the three groups (P＜0.05);as compared with the APP/PS1 model group,the APP/PS1+SCH group had significantly reduced RAGE mRNA expression in the hippocampal area (P＜0.05).(4) Western blotting results showed that RAGE and p-p38 protein expression levels in two parts of mice of APP/PS1+SCH group were significantly reduced as compared with those in the APP/PS1 model group (P＜0.05).Conclusion SCH may improve the functional status of hippocampal and cortical neurons and improve the spatial exploratory memory ability of APP/PS1 mice by down regulating the RAGE and P38 expressions.

Objective:To evaluate the safety and effectiveness of Kangduo endoscopic surgical robot system for partial nephrectomy.Methods:Consecutive patients with stage T 1 renal tumor meeting the inclusion criteria from the Department of Urology, Peking University First Hospital from December 2020 to February 2021 were prospectively enrolled. All patients underwent partial nephrectomy with the Kangduo endoscopic surgical robot system after signing the informed consent. Clinical data including preoperative, perioperative and postoperative pathology and follow-up were collected. Results:Among the 26 patients, there were 16 males and 10 females, with a median age of 53(33-74) years, and a median body mass index of 25.99(20.90-32.91) kg/m 2. There were 12 cases of left kidney tumor and 14 cases of right kidney tumor. The median tumor diameter was 2.2(1.0-3.5) cm. The median time of warm ischemia was 17.7(7.1-29.2) minutes, and all of them were less than 30 minutes. The median docking time was 4.7(2.3-9.9) minutes, and the median time of robotic arm operation was 65.0 (37.0-155.0) minutes. The median National Aeronautics and Space Administration Task Load Index (NASA-TLX) score was 5.3 (2.0-28.0), and no instrument-related adverse events occurred intraoperatively. The median postoperative hospital stay was 4 (4-5) days. All tumor margins were negative on pathologic reports. No Clavien Ⅱ stage operative complications occurred in all patients during perioperative period and 1 month after the surgery. Conclusions:The partial nephrectomy using the kangduo endoscopic surgical robot system were completed successfully, and no instrument-related adverse events and complications occurred, showing that this surgical system used for partial nephrectomy is safe and effective.

Objective To explore the clinical efficacy of early combined application of parenteral nutrition and enteral nutrition among patients in neurosurgical intensive care unit(NICU).Methods Two hundred fifty-five patients with severe neurological diseases were admitted to NICU of Shanghai Tenth People's Hospital from January 1 to August 31 in 2018.The patients were divided into two groups:traditional enteral nutrition group (control group,n=170),who were treated with enteral nutrition management at the early stage,and early combined application of parenteral and enteral nutrition group (experimental group,n=85),who were at first treated with parenteral nutrition since admission and then enteral nutrition management 72 hours later.The differences of Glasgow outcome scale (GOS),incidence of individual adverse reactions,daily average enteral nutrition,human albumin supplement,daily average fluid supplement,pulmonary infection rate,infection time and albumin level during hospitalization between the two groups were compared.The relationship among the course of enteral nutrition,nutrient content,pulmonary infection and serum albumin level in the experimental group were also discussed.The GOS was predicted by decision tree,random forests,nearest neighbor algorithm,adaboost and bagging.Results There was no significant difference between baseline scores after 1∶2 propensity score matching.The dominance ratio of GOS between the two groups was 1.853 (95％CI:1.018-3.385) (P=0.043).The change of albumin level was not related to the choice of nutritional regimen,but was related to the level of consciousness after admission and the level of basic albumin before admission.The level of consciousness in the experimental group was higher than that of the control group,and the fluid infusion volume was decreased while the daily average enteral nutrition and albumin supplementation were increased,the types of adverse reactions occurred more and earlier (P＜0.05).The misjudgment rate of GOS prediction models ranged from 0.482 to 0.606.Conclusions Compared with traditional early enteral nutrition therapy,early combined parenteral nutrition and enteral nutition can improve the prognosis of patients with severe neurological diseases.

Objective To investigate the effect ofDihuangyinzi (DHYZ)-medicated serum on receptor for advanced glycation end product (RAGE)/p38 miotgen-activated protein kinase (MAPK) /nuclear factor (NF)-κB pathway in SH-SY5Y cells induced by Aβ1-42.Methods Male SD rats were randomly divided into normal control group and experimental group (n=20);natural sera medium and DHYZ sera medium were prepared.(1) SH-SY5Y cells were divided into control group,model group and DHYZ treatment group;natural sera medium,natural sera medium+Aβ1-42 oligomer,and DHYZ sera medium+Aβ1-42 oligomer were given to the cells,respectively.Westem blotting was used to detect the protein expressions of NF-κB p65,p38 and phosphorylate (p)-p38.(2) SH-SY5Y cells were given DHYZ sera medium+Aβ1-42 oligomer treatment,and at different time points of Aβ1-42 oligomer treatment (15 min,30 min,60 min,12 h,24 h,48 h and 72 h),Western blotting was used to detect the protein expressions of p38 and p-p38.(3) SH-SY5Y cells were divided into 6 groups:mock-transfected RAGE blank group,transfected RAGE blank group,mock-transfected RAGE model group,transfected RAGE model group,mock-transfected RAGE herb group and transfected RAGE herb group;herb groups were given DHYZ-medicated serum;inflammatory factors,interleukin (IL)-1β,IL-6,and tumor necrosis factor (TNF)-a,were measured by ELISA and cytometric bead array.Results (1) As compared with model group,DHYZ treatment group had significantly decreased NF-κB p65 and p-p38/p38 protein expression.(2) The p-p38 protein expression began to increase 30 min after Aβ1-42 treatment,reached to its peak level 24 h after Aβ1-42 treatment,and began to decrease 48 h after Aβ1-42 treatment.(3) The IL-1β,IL-6 and TNF-α levels were increased significantly in the transfected RAGE model group as compared with those in the mock-transfected RAGE model group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were increased significantly in the transfected RAGE herb group as compared with those in the mock-transfected RAGE herb group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were decreased significantly in the mock-transfected RAGE herb group as compared with those in the mock-transfected RAGE model group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were decreased significantly in the transfected RAGE herb group as compared with those in the transfected RAGE model group (P＜0.05).Conclusion DHYZ-medicated serum could inhibit the RAGE-p38 pathway and improve the inflammatory reaction in Aβ1-42-induced SH-SY5Ycells transfected with RAGE gene to protect the SH-SY5Y cells.