Molecularly engineered truncated tissue factor with therapeutic aptamers for tumor-targeted delivery and vascular infarction

Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy. Among vascular coagulation agents, the extracellular domain of coagulation-inducing protein tissue factor, truncated tissue factor (tTF), is the most widely used. Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation, free tTF cannot be used for cancer treatment on its own but must be combined with other moieties. We here developed a novel, tumor-specific tTF delivery system through coupling tTF with the DNA aptamer, AS1411, which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells. Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors, thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects. This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.

Platelet membrane-based and tumor-associated platelettargeted drug delivery systems for cancer therapy / 医学前沿

Platelets have long been known to play critical roles in hemostasis by clumping and clotting blood vessel injuries. Recent experimental evidence strongly indicates that platelets can also interact with tumor cells by direct binding or secreting cytokines. For example, platelets have been shown to protect circulating cancer cells in blood circulation and to promote tumor metastasis. In-depth understanding of the role of platelets in cancer progression and metastasis provides promising approaches for platelet biomimetic drug delivery systems and functional platelet-targeting strategies for effective cancer treatment. This review highlights recent progresses in platelet membrane-based drug delivery and unique strategies that target tumor-associated platelets for cancer therapy. The paper also discusses future development opportunities and challenges encountered for clinical translation.

The effect of different BIS value on the early postoperative cognitive function and S100βprotein in elderly patients undergoing abdominal surgery / 临床麻醉学杂志

Objective To investigate the effects of different BIS values on postoperative cogni-tive dysfunction (POCD)and S100βprotein(S100β)in the early stage of postoperation.Methods Fifty patients who were scheduled for selective abdominal surgery under general anesthesia (male 34 cases, female 1 6 cases,aged 65 to 75 years,ASA Ⅰ or Ⅱ)were randomly divided into two groups:light anesthesia group (group L,n =25,BIS value was maintained at 50 to 59)and deep anesthesia group (group D,n =25,BIS value was maintained at 30 to 39).BP,HR,SpO 2 ,ECG,PET CO 2 ,inhaled anes-thetic concentration and BIS values were recorded on time points of 5 minutes after the patients ente-ring the operating room (T0 ),before endotracheal (T1 ),intubation (T2 ),incision (T3 ),two hours after incision (T4 ),three hours after incision (T5 )and at the end of surgery (T6 ).The procedure du-ration,anesthesia time,dosages of propofol,fentanyl,midazolam and VAS scores on 1 d after sur-gery were also recorded.Blood samples were collected on time points of 10 min before anesthesia,im-mediately after surgery and 24,48 h after operation.S100β concentration were detected.Mini-mental State Examination (MMSE)score and Trail Making Test (TMT)completion time were recorded on 1 d before surgery and 1,3,7 d after surgery.Results BIS value of group D were lower than group L on T2 ,T3 and T4 .The propofol dosage of group D was significantly greater than that in group L (P <0.05 ).The concentration of serum S100βincreased significantly immediate and 48 h after operation in both groups compared with 10 min before anesthesia(P < 0.05).It was still higher 24 hours after op-eration than before anesthesia.But there was no statistic difference.Compared with the end of surger-y,the concentration of serum S100βin two groups on 24 h after surgery were significantly decreased (P < 0.05 ).The concentration of serum S100β in group L on the end of surgery and 24 h after surgery were higher than that in group D significantly (P <0.05).Compared with 1 d before surgery, postoperative 1 d MMSE scores in two groups and postoperative 3 d MMSE score in group L de-creased significantly (P <0.01).Compared with postoperative 3 d,postoperative 7 d MMSE score in group L increased significantly (P <0.01).Postoperative 1,3 d MMSE score in group D were signifi-cantly higher than group L (P <0.05).Compared with 1 d before surgery,TMT completion time in two groups on 1 d after surgery were significantly prolonged (P <0.01 ).Compared with 1 d after surgery,TMT completion time in two groups on 3 d after surgery were significantly shortened (P <0.01).Compared with 3 d after surgery,TMT completion time in group L on 7 d after surgery was significantly shortened (P <0.01 ).TMT completion time in group D on 1,3 d postoperative were significantly shorter than group L (P <0.05).POCD incidence of group D on 1 d after surgery was lower than that in group L (P < 0.05).Conclusion Different depth of anesthesia can ensure hemo-dynamic balance in old patients during surgery and after surgery.When BIS value was maintained at 30 to 39,it had lower S100βprotein levels,lower incidence of early POCD and a lesser degree of post-operative cognitive dysfunction.

In situ rat intestine absorption of paclitaxel-loaded solid lipid nanoparticles modified with cell-penetrating peptides / 药学学报

To investigate the rat intestinal absorption of stearic acid-octaarginine (SA-R8) modified solid lipid nanoparticles containing paclitaxel (SA-R8-PTX-SLN), compared with the commercially available preparation of PTX (Taxol) and PTX-loaded solid lipid nanoparticles (PTX-SLN), the in situ intestinal absorption of SA-R8-PTX-SLN was investigated by means of single-pass rat intestinal perfusion technique. The absorptions of the preparations were investigated at different intestinal segments, different drug concentrations and in the presence of P-glycoprotein inhibitor (verapamil). The results showed that PTX could be absorbed at each intestinal segment and the three preparations all showed maximum absorptions at the duodenum. The cumulative absorptions of three preparations at each intestinal segment appeared SA-R8-PTX-SLN > PTX-SLN > Taxol (P 0.05). SA-R8 and SLN might both effectively improve the oral absorption of PTX in the intestinal tract.

Investigation on the related prognostic factors of the patients with thyroid microcarrinoma / 中国基层医药

Objective To explore the related prognostic factors of the patients with thyroid microcarcinoma.Methods Clinical data,including clinical,pathologic,and therapeutic factor of 203 patients with thyroid microcarcinoma admitted were analyzed retrospectively.Results The cause specific survival and locoregional failure free survival rates at 10 years were 100.0% and 91.4% , respectively.Univariate analysis showed that multifocality, cervical lymph node metastasis and radioiodine treatment was associated with prognosis.Multivariate analysis revealed that cervical lymph node metastasis was the only independent prognostic factor for locoregional failure free survival.The risk of locoregional recurrence increased 2.5 folds when lymph nodes metastasis occurred at presentation.Conclusion The ratio of thyroid microcarcinoma to thyroid carcinoma increased yearly and the overall survival rate of thyroid microcarcinoma was excellent.Of all the prognostic factors,lymph node metastasis was the most important one related to survival.

Prevention and treatment of recurrent laryngeal nerve injury during operation in patients with thyroid cancer / 中国基层医药

Objective To investigate the causes, prevention and treatment of recurrent laryngeal nerve (RLN) injury during operation in patients with thyroid cancer. Methods Clinical data of 192 patients undergone thyroidectomy operation were reviewed. Results RLN was exposed during operation in 192 patients. There were 3 cases of RLN injury, then RLN anastomosis was happened immediately during operation. It was significantiy improved in pronunciation after operation. 2 ～ 3 d after surgery, transitory hoarseness was observed in 3 patients. Unilateral RLN resection performed in 1 case with cancer involving RLN. Conclusions There were some causes of RLN injury. Exposure of RLN selectively,delicate operation and thyroid gland surgery specialist were the key point for prevention of the injury of RLN. Once RLN injury occured ,repairing should be performed as soon as possible.