Objective:To construct double-layered controlled release system containing SDF-1 and rhBMP-2 molecules and to study the release profile of the system in vitro.Methods:The polylactic acid/chitosan(PLA/CS)nanoparticles were prepared with “emulsification-solution evaporation method”,the preparation parameters were determined by orthogonal test design.The particle size was observed by nanoparticle size analyzer,the morphology of the nanoparticles was observed with electron microscope.Then rhBMP-2 and SDF-1 were loaded into the nanoparticles in the process of emulsification,the loading efficiency and encapsulation efficiency were calculated and in vitro release was observed.Results:The double-layer nanoparticles showed spherical geometry,smooth surface and complete separation. The average particle size of the nanoparticles was (542.33 ±14.38)nm;The drug loading and incorporation efficiency of rhBMP-2 were (82.41 ±1.05)% and (24.67 ±0.43)ng/mg,those of rhBMP-2 were (75.58 ±0.84)% and (22.63 ±0.41)ng/mg,respectively. The release time of the drug from the system sustained over at least 30 days,the release profile of both drugs showed “biphasic release”. The cumulative release rate of SDF-1 and rhBMP-2 was 72.85% and 91.01% in 30 days respectively.Conclusion:The SDF-1 and rh-BMP-2 loaded PLA/CS nanoparticles have excellent morphology,high entrapment and good sustained-release in vitro.

BACKGROUND:Previous studies have suggested that the risks for coronary atherosclerotic plaque progression and in-stent restenosis are increased in patients with coronary heart disease combined with type 2 diabetes. OBJECTIVE:To explore the predictive factors for in-stent late loss and non-culprit coronary lesion progression in patients with type 2 diabetes mel itus. METHODS:A total of 399 stenting patients were enrol ed, including 179 diabetic patients and 220 non-diabetic patients. The clinical materials, angiography parameters and biochemical markers were col ected. The difference between the two groups was compared, and also we conducted subgroup analysis in the diabetic patients. Low-density lipoprotein cholesterol, hemoglobin A1c, fibrinogen and high-sensitivity C-reactive protein were detected at days 3, 120, 210 and 360 after stenting. RESULTS AND CONCLUSION:Compared with non-diabetic patients, the stent length (P=0.18) was longer and the stent diameter (P=0.002) was smal er in the diabetic patients. The minimal lumen diameters of post-procedure and fol ow-up angiography in the diabetic group were significantly decreased (P=0.001, P=0), and the diabetic patients also showed severe coronary artery stenosis instantly and within the fol ow-up after stenting (P=0.038, P=0.004). The fol ow-up angiography showed that the diabetic patients had more late loss and restenosis (P=0, P=0.097). Furthermore, in the subgroup analysis of diabetic patients, the levels of hemoglobin A1c, fibrinogen and high-sensitivity C-reactive protein were significantly increased in the patients with restenosis and non-culprit lesion progression. These findings indicate that diabetic patients appear to have the higher incidence of restenosis and non-culprit lesion progression. Moreover, hemoglobin A1c, fibrinogen and high-sensitivity C-reactive protein are effective predictors for in-stent late loss and non-culprit coronary lesion progression.

The Borf1 protein is encoded by an immediate-early gene of the bovine foamy virus (BFV) and plays a key role in the viral life cycle. Borf1 is a DNA binding protein which can transactivate both the long terminal repeat (LTR) and the internal promoter (IP) of BFV by specifically binding to the transactivation responsive element (TRE). To analyze the subcellular localization of Borf1 during the BFV life cycle, this gene was cloned into a prokaryotic expression vector and expressed in a soluble form. After the purification and immunization, we raised the mouse anti-Borf1 serum with a high titer based on ELISA results. Western blot analysis showed that the antiserum could specifically recognize the Borf1 protein that was expressed in 293T cells. With this specific serum, we revealed the nuclear and cytoplasmic localization of Borf1 in HeLa cells that was transfected with Borf1. Moreover, the immuno-fluorescence assay also showed that the localization of Borf1 during the infection and transfection of BFV was identical.

Objective: To investigate the correlation between FIB-4 and the clinicopathological characteristics and prognosis of patients with hepatocellular carcinoma (HCC) after curative resection. Methods: From January 2009 to December 2012, the clinicopathological and follow-up data of 245 patients with HCC after curative resection were retrospectively studied. Their survival was calculated using the Kaplan-Meier method. The Cox proportional hazard regression model was used for the multivariate analysis. Results: According to FIB-4 index, patients were divided into two subgroups: FIB-4Ⅰ(≤3.25) and FIB-4Ⅱ(>3.25). FIB-4 could predict liver cirrhosis severity (Ishak grade, Grade 1-5 vs. Grad 6, r=0.681, P<0.001). It was associated with liver function such as:aspartate transaminase (P<0.001)、total bilirubin (P=0.009)、albumin (P=0.001) and platelet count (P<0.001) other than tumor clinicopathologic features. Both univariate and multivariate analysis showed FIB-4 could predict the prognosis of HCC patients (Overall survival: P=0.037 and 0.011; Recurrencefree survival: P=0.027 and P=0.043, respectively). Conclusion: The preoperative FIB-4 index could be used as a prognostic marker for the prognosis of HCC after curative hepatectomy.

Objective To investigate the mechanism of recurrent laryngeal nerve injury during total thyroidectomy.Methods The clinical data of 36 patients suffering from recurrent laryngeal nerve injury in total thyroidectomy from 2003 to 2014 was analyzed retrospectively.Results 21 cases had temporary recurrent laryngeal nerve injury while 16 cases had permanent injury.The cases of injury included giant thyroid goitre,with variation of recurrent laryngeal nerve,undergoing secondary surgery,with tumor invasion and complicating thyroiditis.During the first surgery,the incidence of temporary recurrent laryngeal nerve injury was 0.43％,and the incidence of permanent damage was 0.27％.The temporary and permanent injury incidence of secondary surgery after initial subtotal thyroidectomy was 4.59％ and 4.59％,respectively.For patients with grade 3 thyroid gland,that was 1.81％ and 0.30％,respectively and 0.51％,0.72％ respectively in malignant cases.In cases complicating thyroiditis temporary recurrent laryngeal nerve injury occurred in 1.01％.Conclusions There is increased risk of recurrent laryngeal nerve injury in giant goiter cases undergoing secondary operations.Hence it is suggested that initial surgical procedure be hemithyroidectomy or total thyroidectomy

Objective To evaluate the effect of modified Maze lines plus pulmonary vein (PV) isolation created by radiofrequency catheter ablation (RFCA) on atrial wall guided by a novel geometry mapping system in the treatment of elderly patients with paroxysmal atrial fibrillation (PAF). Methods After regular electrophysiological study, transseptal punctures were achieved twice with Swartz L1 and R1 sheaths. PV angiographies were conducted to evaluate their orifices and branches. A balloon electrode array catheter with 64 electrodes was put in the middle of the left atrium. Atrium geometry was constructed using Ensite 3000 Navx system. Two RFCA lesion loops and three lines (modified Maze) were created on left and right atrial walls. Each lesion point was ablated for 30 seconds with preset temperature 50 (ae) and energy 30W. The disappearance or 80% decrease of the amplitude of target atrial potential and 10 to 20(|), decrease of ablation impedance were used as an index of effective ablation. Results A total of 11 patients (7 male and 4 female, mean age, 68.7±5.1 years) were enrolled. PAF history was 7.9±4.5 years. PAF could not be prevented by mean 3.1±1.6 antiarrhythmic agents in 6.3±3.4 years. None of the patients had complications with structural heart disease or stroke. Left atrial diameter was 41.3±3.6 mm and LVEF was 59.2±3.7% on echocardiography. Two loops and three lines were completed with 67.8±13.1 (73-167) lesion points. Altogether 76-168 (89.4±15.3) lesion points were created in each patient. PAF could not be provoked by rapid burst pacing up to 600 beat per minute delivered from paroxysmal coronary sinus electrode pair.Complete PV electrical isolation was confirmed by three-dimensional activation mapping. Mean procedure time was 2.7±0.6 hours and fluoroscopy time was 17.8±9.4 minutes. Patients were discharged with oral aspirin and without antiarrhythmic agents. During follow up of 6.5±1.8 months, seven patients were PAF symptom free (63.6%). PAF attacks were decreased more than 70% in two patients (18.2%). PAF frequency did not change in another two patients (18.2%). Conclusions Ensite 3000 Navx guided modified Maze lines plus PV isolation on the atrial wall is safe and feasible in the elderly patients. It has the advantages of exact procedural endpoint, shorter X-ray exposure, fewer complications and satisfied long-term effect PAF control.

Objectives:To report the clinical experience of combined interventional procedures in the treatment of elderly patients with coexisting two or more cardiovascular diseases in our medical center, and to assess the feasibility, safety and therapeutic efficacy of this management strategy. Methods : Patients were selected to the study if: 1) age ＞65 years; 2) with coexistence of two or more cardiovascular diseases which are indications for interventional therapy; 3) patients' general condition and organ functions allow the performance of combined multiple procedures; 4) the predicted procedure time is within 150 min; 5) the predicted contrast medium dosage is within 300 ml. The criteria we analyzed included procedural type, rocedural time, fluoroscopy time, dosage of contrast medium, success rates of the procedures, complications and in-hospital mortality. All patients were followed up for 30.4 ± 9.3 months,to determine the all-cause mortality, recurrence rates and adverse cardiac events. Results : From January 2000 to December 2004,combined interventional procedures were performed on 136 patients, with 2 procedures on 134 patients and 3 procedures on 2 patients.The mean procedure time was 115.4±11.6 min, the mean fluoroscopy time was 35.7±9.3 min, and the mean dosage of contrast medium used was 183.6±19.4 ml. Procedural success rate was 100%, no procedure related death or major complications occurred.Conclusion: Performed by a competent team, combined interventional procedures in elderly patients with multiple cardiovascular diseases were feasible and relatively safe.

OBJECTIVETo investigate the value of Qingyi Decoction (QYD) and Glauber's salt (GS) for treatment of severe acute pancreatitis (SAP).

METHODSSixty-five patients with SAP were randomly assigned to two groups, the treated group (33 patients) and the control group (32 patients). They received the same therapy except that to the patients in the treated group, QYD was given through naso-gastric tube and GS was applied externally.

RESULTSCompared with those in the control group, the alleviating time of clinical symptoms, such as abdominal pain and distention, time of hospitalization and time of blood amylase recovery in the treated group were shorter, with lesser complications and lower rate of transferring to operation (all with P < 0.05), showing a better efficacy in all aspects, but the mortality in the two groups was not different (P > 0.05).

CONCLUSIONCombined use of QYD and GS has significant therapeutic effect for treatment of SAP.

Adult ; Aged ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis, Acute Necrotizing ; drug therapy ; Phytotherapy ; Prospective Studies ; Sulfates ; therapeutic use ; Treatment Outcome

Objective To evaluate the feasibility and efficacy of intravascular optical coherence tomography (OCT) in the assessment of plaque characteristics and drug eluting stent deployment quality in the elderly patients with unstable angina (UA) and non-ST segment elevation myocardial infarction (NSTEMI). Methods OCT was used in elderly patients undergoing percutaneous coronary interventions.Fifteen patients, 9 males and 6 females with mean age of 72.6±5.3 years (range 67-92 years) were enrolled in the study. Images were obtained before initial balloon dilatation and following stent deployment. The plaque characteristics before dilation, vessel dissection,tissue prolapse, stent apposition and strut distribution after stent implantation were evaluated. Results Fifteen lesions were selected from 32 angiographic lesions as study lesions for OCT imaging after diagnostic coronary angiography. There were 7 lesions in the left anterior descending artery, 5 lesions in the right coronary artery and 3 lesions in the left circumflex coronary artery. Among them,12 (80.0%) were lipid-rich plaques, and 10 (66.7%) were vulnerable plaques with fibrous cap thickness 54.2±7.3 μm. Seven ruptured culprit plaques (46.7%) were found; 4 in UA patients and 3 in NSTEMI patients. Tissue prolapse was observed in 11 lesions (73.3%).Irregular stent strut distribution was detected in 8 lesions (53.3%). Vessel dissections were found in 5 lesions (33.3%). Incomplete stent apposition was observed in 3 stents (20%) with mean spacing between the struts and the vessel wall 172±96 mm (range 117-436 mm).Conclusions 1) It is safe and feasible to perform intravascular OCT to differentiate vulnerable coronary plaque and monitor stent deployment in elderly patients with UA and USTEMI. 2) Coronary plaques in elderly patients with UA and USTEMI could be divided into acute ruptured plaque, vulnerable plaque, lipid-rich plaque, and stable plaque. 3) Minor or critical plaque rupture is one of the mechanisms of UA in elderly patients. 4) Present drug eluting stent implantation is complicated with multiple tissue prolapses which are associated with irregular strut distributions. 5) The action and significance of tissue prolapse on acute vessel flow and in-stent thrombus and restenosis need to be further studied.

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.