Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.

Construction of prediction models for prolonged length of postoperative hospital stay in patients undergoing thoracoscopic lobectomy / 中华麻醉学杂志

Objective:To construct the prediction model for the prolonged length of postoperative hospital stay in the patients undergoing thoracoscopic lobectomy.Methods:The patients of both sexes, aged ≥18 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, who received elective thoracoscopic lobectomy with general anesthesia from March 2016 to February 2019 in our hospital, were selected, their clinical data were collected, and the patients were pathologically diagnosed with non-small-cell lung cancer after operation.Basic information (sex, age, smoking history), previous history (dyslipidemia, hypertension, diabetes, cardiovascular and cerebrovascular diseases, peripheral vascular diseases, chronic obstructive pulmonary diseases), allergy history, other tumor history, surgical resection site, anesthetic factors (intraoperative use of non-steroidal anti-inflammatory drugs and glucocorticoids, duration of anesthesia, intraoperative epidural anesthesia + postoperative epidural analgesia) and postoperative complications (pleural effusion, pneumothorax, atelectasis) was collected.The patients were divided into 2 groups according to whether the length of postoperative hospital stay was prolonged: normal group (≤ 7 days) and prolonged group (>7 days).Logistic regression analysis was used to identify the predictors for prolonged length of postoperative hospital stay.The regression model for prediction of prolonged length of postoperative hospital stay was constructed based on the TensorFlow deep learning framework, and the efficacy of prediction was evaluated.A deep neural network was further established based on the TensorFlow framework to construct a classification prediction model for prolonged length of postoperative hospital stay, and the efficacy of prediction was assessed, further comparing it with the prediction model constructed by the traditional machine learning method.Results:A total of 428 patients were finally enrolled in the study.The results of multivariate logistic regression analysis showed that age and anesthesia duration were the risk factors for the prolonged length of postoperative hospital stay, and female, other tumor history and resection of right middle lobe were the protective factors ( P<0.05).The performance of the regression model proved ineffective, getting 2.16 mean absolute error and 11.05 mean square error on the training set, 2.14 mean absolute error and 11.73 mean square error on the test set.The classification model achieved better score with accuracy 75.58%, F1-measure 0.553 and area under the receiver operating characteristic curve 0.702 on the test set, however, it showed no better performance than that of 4 other prediction models established by 4 traditional machine learning methods, specifically Logistic Regression, Random Forest, Gradient Boosting and Support Vector Machine. Conclusions:Sex, age, surgical resection site, other tumor history and duration of anesthesia can serve as the predictors, and a classification prediction model for prolonged length of postoperative hospital stay is constructed based on a deep neural network in the patients undergoing thoracoscopic lobectomy.

Safety analysis of delayed use of nasointestinal tube / 中国医师杂志

Objective:To investigate the indwelling time of nasointestinal tube and the safety of delayed use, and to analyze the main influencing factors.Methods:216 patients with indwelling nasointestinal tube were analyzed retrospectively by designing a survey from 2018 to 2020. Receiver operating characteristic curve (ROC) analysis method was used to analyze the threshold of pipe blocking time.Results:Among the 216 patients, the shortest indwelling time was 7 days and the longest was 120 days. The incidence rate of tube blockage, aspiration and accidental extubation was 6.02%(13/216), 2.78%(6/216) and 1.39%(3/216), respectively. Statistical analysis of 13 patients with tube occlusion showed that the incidence of tube occlusion was related to the indwelling time and the speed of pumping (χ 2=46.056, 36.564, P<0.05). In addition, the duration of nasointestinal tube use not only affected the incidence of tube occlusion, but also was related to the incidence of aspiration. With the prolongation of catheter insertion time, the rate of tube occlusion and the incidence of aspiration also increased significantly (χ 2=13.190, P<0.05). ROC curve was used to analyze the correlation between the indwelling time of the feeding tube and the occlusion. The area under the ROC curve was 0.933 (95% CI: 0.886-0.981, P<0.001), the Youden index was 0.829, and the cut-off value of the best indwelling time was 52.5 d. The sensitivity and specificity of the method for determining the occurrence of pipe blockage were 92.3% and 90.6%. Conclusions:It is safe and feasible to extend the indwelling time of nasointestinal tube appropriately, which can reduce the discomfort caused by frequent replacement of nasointestinal tube in patients with long-term enteral nutrition, and reduce the medical cost at the same time. However, when the indwelling time exceeds the threshold, the probability of tube blockage increases significantly, so we should maintain the catheter or replace it in time.

Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity

The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases. Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40L interaction. Despite this progress, many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered. In this review we summarize the impact of the OX40-OX40L interaction on T cell subsets, including Th1, Th2, Th9, Th17, Th22, Treg, Tfh, and CD8 T cells, to gain a comprehensive understanding of anti-OX40 mAb-based therapies. The potential therapeutic application of the OX40-OX40L interaction in autoimmunity diseases and cancer immunotherapy are further discussed; OX40-OX40L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases. We also explore the rationale of targeting OX40-OX40L interactions in cancer immunotherapy. Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells. When combined with other therapeutic treatments, such as anti-PD-1 or anti-CTLA-4 blockade, cytokines, chemotherapy, or radiotherapy, the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced. These data collectively suggest great potential for OX40-mediated therapies.

Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma

Due to the critical correlation between inflammation and carcinogenesis, a therapeutic candidate with anti-inflammatory activity may find application in cancer therapy. Here, we report the therapeutic efficacy of celastrol as a promising candidate compound for treatment of pancreatic carcinoma naïve neutrophil membrane-coated poly(ethylene glycol) methyl ether--poly(lactic--glycolic acid) (PEG-PLGA) nanoparticles. Neutrophil membrane-coated nanoparticles (NNPs) are well demonstrated to overcome the blood pancreas barrier to achieve pancreas-specific drug delivery . Using tumor-bearing mice xenograft model, NNPs showed selective accumulations at the tumor site following systemic administration as compared to nanoparticles without neutrophil membrane coating. In both orthotopic and ectopic tumor models, celastrol-loaded NNPs demonstrated greatly enhanced tumor inhibition which significantly prolonged the survival of tumor bearing mice and minimizing liver metastases. Overall, these results suggest that celastrol-loaded NNPs represent a viable and effective treatment option for pancreatic carcinoma.

Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer

Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin (DOX) and Toll-like receptor 7 agonist imiquimod (IMQ) in low molecular weight heparin (LMWH)-d--tocopheryl succinate (TOS) micelles (LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles (LT-DOX) generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles (LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1 (PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8 CTLs/T and CD4 T/T. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer.

Controversy and agreement of lymph node dissection in radical resection for esophageal cancer / 中华消化外科杂志

Currently esophagectomy is still the main procedure for the treatment of esophageal cancer.Optimal lymph node dissection in esophagectomy is the most important link.However,the issues about lymphadenectomy have always been controversial,including two-field or three-field dissection,numbers of harvest lymph nodes and sentinel lymph node,while some consensuses on lymph node dissection are formed in clinical practice under controversy.

Perioperative Venous Thromboembolism (VTE) Prophylaxis in Thoracic Cancer Patients: Chinese Experts Consensus - Interpretation of Clinical Significance of D-dimer / 中国肺癌杂志

The risk of perioperative venous thromboembolism (VTE) is pretty high in thoracic cancer patients. Perioperative VTE influences the recovery of patients after operation and quality of life in the future, even seriously leading to death. To strengthen the knowledge and attention of thoracic surgeons on perioperative VTE in thoracic cancer patients, China National Research Collaborative Group on VTE in Thoracic Surgery released the edition of VTE prophalaxis in thoracic cancer patients: Chinese experts consensus in 2018. This article is to interpret the diagnostic value and risk prediction value of D-dimer in VTE in detail, and briefly introduce the role of other biomarkers in VTE of tumor patients. The consensus interpretation aims to deepen the understanding of thoracic surgeons on the clinical significance of D-dimer in VTE.

Implantable sandwich PHBHHx film for burst-free controlled delivery of thymopentin peptide

Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin (TP5). To this end, implantable sandwich poly (hydroxybutyrate--hydroxyhexanoate) (PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. release studies revealed that sandwich films had nearly no burst release. release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4/CD8 values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.

Therapeutic effect of acupoint catgut embedding on gastrointestinal dysfunction after surgery in patients with severe traumatic brain injury: a prospective randomized controlled clinical trial / 中国中西医结合急救杂志

Objective To evaluate the therapeutic effect of acupoint catgut embedding on gastrointestinal dysfunction after surgery in patients with severe traumatic brain injury.Methods Sixty-eight consecutively hospitalized patients with gastrointestinal dysfunction after surgery in patients with severe traumatic brain injury admitted to the Department of Intensive Care Unit (ICU) in the First Affiliated Hospital of Zhejiang University of Chinese Medicine from January 2015 to December 2015 were enrolled.Six of those patients were withdrawn from the course of observation,and actually only 62 patients entered the study.They were divided into an observation group (32 cases) and a control group (30 cases) by random number table.All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days.The observation group was additionally treated with acupoint catgut embedding.The control group took mosapride tablets via a nasogastric tube 5 mg,3 times a day.Intra-abdominal pressure (IAP),gastric residual volume (GRV),time for reaching standard enteral nutrition,serum diamine oxidase(DAO),D-Lactate activity,incidence of hospital-acquired pneumonia (HAP),hospitalization days in ICU,28-day mortality and adverse reactions of acupoint catgut embedding were observed in the two groups.Results After treatment,the levels of IAP,DAO,D-lactic acid were lower than those before treatment,GRV was less than that before treatment in the two groups,and after treatment for 7 days the changes were more significant in the observation group [IAP (cmH2O,1 cmH2O =0.098 kPa):12.42±3.11 vs.17.70 ± 2.98,GRV (mL):129.54 ± 57.54 vs.242.91 ± 99.29,DAO (U/L):9.06± 2.84 vs.13.60 ± 7.16,D-Lactate (mg/L):16.47 ± 5.39 vs.26.29 ± 9.62,all P ＜ 0.01].Days of mechanical ventilation (days:6.97 ± 4.13 vs.9.23 ± 4.61),time for reaching standard enteral nutrition (days:4.25 ± 3.15 vs.5.50 ± 3.12) and hospitalization days in ICU (days:9.50± 4.03 vs.12.20 ± 6.38) in observation group were significantly shorter than those in control group (all P ＜ 0.05).The incidence of HAP [15.6％ (5/32) vs.40.0％ (12/30)] and 28-day mortality [3.1％ (1/32) vs.6.7％ (2/30)] in observation group were obviously lower than those in control group.The patients in observation group had no significant adverse reactions of acupoint catgut embedding.Conclusions Acupoint catgut embedding therapy is not only easy to operate,but also can effectively improve gastrointestinal motility and intestinal barrier function in patients with gastrointestinal dysfunction after surgery of severe head injury,thus it is beneficial to reaching the enteral nutritional goal in less time,reducing the incidence of HAP,shortening the hospitalization time in ICU and promoting the recovery of the patients.

Preparation and evaluation of a phospholipid-based injectable gel for the long term delivery of leuprolide acetaterrh

A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-a-month injection of LA-loaded SPME (SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.

Comparison of the lymph node dissection and complications between video-assisted thoracoscopic (VATS) esophagectomy and conventional esophagectomy via right thoracotomic / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Video-assisted thoracoscopic (VATS) esophagectomy has been performed for more than 10 years in China. However, compared with the conventional esophagectomy via right thoracotomy, whether VATS esophagectomy has more advantages or not in the lymph node (LN) dissection and prevention of perioperative complications is still controversial and deserves to be further investigated. The aim of this study was to explore whether there are significant differences in this issue between the two surgical modalities or not.</p><p><b>METHODS</b>The results of lymph node dissection and perioperative complications as well as other parameters in the patients treated by VATS esophagectomy and those by conventional esophagectomy via right thoracotomy at our department from May 1, 2009 to July 30, 2013 were compared using SPSS 16.0 in order to investigate whether there was any significant difference between these two treatment modalities in the learning curve stage of VATS esophagectomy.</p><p><b>RESULTS</b>One hundred and twenty-nine cases underwent VATS esophagectomy between May 1, 2009 and July 30, 2013, and another part 129 cases with the same preoperative cTNM stage treated by conventional esopahgectomy via right thoracotomy were selected in order to compare the results of lymph node dissection and perioperative complications as well as other parameters between those two groups of patients. There were no significant differences in the sex, age, lesion locations and cTNM stage between these two groups. The total LN metastatic rate in the VATS esophagectomy group was 35.7% and that of the conventional esophagectomy group was 37.2% (P > 0.05). The total average number of dissected lymph nodes was 12.1 vs. 16.2 (P < 0.001). The average dissected LN stations was 3.2 vs. 3.6 (P = 0.038). The total average number of dissected LN along the left recurrent laryngeal nerve was 2.0 vs. 3.7 (P = 0.012). The total average number of dissected LN along the right recurrent laryngeal nerve was 2.9 vs. 3.4 (P = 0.231). However, there was no significant difference in the total average number of dissected LN in the other thoracic LN stations, and in the perioperative complications between the two groups. The total postoperative complication rate was 41.1% in the VATS group versus 42.6% in the conventional group (P = 0.801). The cardiopulmonary complication rate was 25.6% vs. 27.1% (P = 0.777). The death rate was the same in the two groups (0.8%). The VATS group had less blood infusion (23.2% vs. 41.8%, P = 0.001) and shorter hospital stay (15.9 days vs. 19.2 days, P = 0.049) but longer operating time (161.3 min vs. 127.8 min, P < 0.01).</p><p><b>CONCLUSIONS</b>In the learning curve stage of VATS esophagectomy, compared with the conventional esophagectomy, less LN number and stations can be dissected in the VATS group due to un-skillful VATS manipulation, especially it is more difficult in the LN dissection along the left recurrent laryngeal nerve. Therefore, it is more suitable to select patients with early esophageal cancer without obvious enlarged lymph nodes for VATS esophagectomy in the learning curve stage.</p>

Study on Serum Pharmacochemistry of Ke-Luo-Xin Capsule / 世界科学技术-中医药现代化

This article was aimed to study the main effective substances and characteristics of Ke-Luo-Xin (KLX) capsule. HPLC-DAD system was applied in the establishment of HPLC finger prints of serum of rats after taking KLX capsule. And then, serum samples taken KLX capsule, blank blood serum, and single crude drugs were com-pared. Constituents absorbed into the serum were determined by HPLC-DAD system. The results showed that meth-ods for serum HPLC fingerprinting had good precision, reproducibility and stability. A total of 13 constituents migrat-ing to the blood were detected, of which 9 were prototype constituents, 4 were metabolites. Prototype constituents in-cluded aloeemodin and chrysophanic acid. It was concluded that 13 constituents migrating to the blood may be the main effective substances of KLX capsule.

Self-provided well water solubility of total solid rapid determination method of research / 国际检验医学杂志

Objective To establish a method for determination of total soluble solids (TDS) in self-provided well water .Methods The conductivity meter which has a function of determination of total soluble solid ,and was used to directly determinate the total soluble solids in self-provided well water .Results Compared with national standard method ,the results have no significant differ-ence .The relative standard deviation (RSD) was 0 .17% -0 .22% ,and the recovery rates of standard was 97 .5% -98 .6% .Conclu-sion The method is quick ,simple ,sensitive ,accurate and suitable for rapid determination of large quantities of waters .

Exploration of lymph node metastasis and appropriate lymph node dissection modes in patients with clinical stage I non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the pattern of lymph node metastasis and evaluate the modes and extent of mediastinal lymph node dissection in patients with ≤ 3 cm, clinical stage I primary non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Data of 270 eligible patients who underwent pulmonary resection with systematic lymph node dissection in our hospital between March 2012 and August 2013 were retrospectively analyzed in order to investigate the relationship between the clinicopathological features and lymph node metastatic patterns. Patients with multiple primary carcinomas or non-primary pulmonary malignancies and those who received any chemotherapy or radiotherapy or did not undergo systematic nodal dissection were excluded. The criteria of systematic nodal dissection included the removal of at least six lymph nodes from at least three mediastinal stations, one of which must be subcarinal. The data were analyzed and compared using Chi-square test.</p><p><b>RESULTS</b>The postoperative morbidity rate was 14.8% and no death occurred in this series. The imaging findings showed 34 cases of pure ground glass opacity lesions, 47 partial solid nodules, and 189 solid nodules. Apart from 34 p-GGO lesions, among the other 236 cases, ≤ 1 cm lesions were in 22 cases, 1 cm- ≤ 2 cm lesions in 138 cases, and >2 cm- ≤ 3 cm lesions in 76 cases based on radiologic findings. The pathological types included adenocarcinoma (n = 245), squamous cell carcinoma (n = 18) and other rare types (n = 7). The overall lymph node metastasis rate was 18.9% (51/270), and the incidence of lymph node involvement was 0(0/34) in cancers with p-GGO, 2.1% (1/47) in mixed solid nodules, 26.5% (50/189) in solid nodules, 18.2% (4/22) in nodules ≤ 1 cm, 14.5% (20/138) in 1 cm < nodules ≤ 2 cm, and 35.5% (27/76) in 2 cm < nodules ≤ 3 cm. The metastasis rates of non-specific tumor-draining region lymph nodes detected in the patients with positive and negative lobe-specific lymph node involvement were 20.0%-50.0% vs. 0-2.9% (P < 0.001).</p><p><b>CONCLUSIONS</b>Usually NSCLC with p-GGO nodules has no lymph node metastasis, therefore, systematic nodal dissection may be not necessary. The larger the tumor size is, the higher the lymph node metastatic rate is for mixed or solid nodules. Intraoperative frozen-section examination of the lobe-specific lymph nodes should be performed routinely in patients with ≤ 2 cm stage I NSCLC, and systematic nodal dissection should be done if positive, but it may be not necessary if negative. However, the effectiveness of the systematic selective lymph node dissection still needs to be further confirmed.</p>

Kidney-targeted drug delivery systems

Kidney-targeted drug delivery systems represent a promising technology to improve drug efficacy and safety in the treatment of renal diseases. In this review, we summarize the strategies that have been employed to develop kidney-targeted drug delivery systems. We also describe how macromolecular carriers and prodrugs play crucial roles in targeting drugs to particular target cells in the kidney. New technologies render it possible to create renal targeting conjugates and other delivery systems including nanoparticles and liposomes present promising strategies to achieve the goal of targeting drugs to the kidney.

A detachable coating of cholesterol-anchored PEG improves tumor targeting of cell-penetrating peptide-modified liposomes

Cell-penetrating peptides (CPPs) have been widely used to enhance the membrane translocation of various carriers for many years, but the non-specificity of CPPs seriously limits their utility in vivo. In this study, cholesterol-anchored, reduction-sensitive PEG (first synthesized by our laboratory) was applied to develop a co-modified liposome with improved tumor targeting. Following optimization of the formulation, the in vitro and in vivo properties of the co-modified liposome were evaluated. The co-modified liposome had a much lower cellular uptake and tumor spheroid uptake, but a much higher tumor accumulation compared to CPP-modified liposome, indicating the non-specific penetration of CPPs could be attenuated by the outer PEG coating. With the addition of exogenous reducing agent, both the in vitro and in vivo cellular uptake was markedly increased, demonstrating that the reduction-sensitive PEG coating achieved a controllable detachment from the surface of liposomes and did not affect the penetrating abilities of CPPs. The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.

Role of conventional pulmonary function tests and stair climbing test in the prediction of postoperative cardiopulmonary complications in non-small cell lung cancer patients after surgery / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate and compare the value of stair climbing tests and conventional pulmonary function tests in the prediction of postoperative cardiopulmonary complications in non-small cell lung cancer patients underwent surgery.</p><p><b>METHODS</b>From April 1, 2010 to Jan. 30, 2012, a total of 162 patients with thoracic carcinoma underwent stair climbing test (SCT) and conventional pulmonary function tests (PFT) preoperatively. The correlation of postoperative cardiopulmonary complications with the SCT and PFT parameters were analyzed retrospectively using chi-square test, independent sample t test and binary logistic regression analysis.</p><p><b>RESULTS</b>Of the 162 patients, 19 without operation were excluded, due to an advanced stage (9 cases), poor cardiopulmonary function (5 cases), rejecting operation (4 cases) and exploration alone (1 case). 143 cases were eligible and evaluated eventually. Forty-one of the 143 patients (28.7%) had postoperative cardiopulmonary complications, but no death occurred. The patients were stratified into groups based on the time of stair climbing 5 stories (18.36 m, t, <92 s, ≥ 92 s). Exercise oxygen desaturation (EOD) during the stair climbing test (<5%, ≥ 5%) and the difference between the pulse at resting state and the pulse at end of stair climbing test (ΔP, <55 beats/min, ≥ 55 beats/min), respectively. The rate of postoperative cardiopulmonary complications was significantly higher in the group with t ≥ 92 s, EOD ≥ 5% and ΔP < 55 beats/min (38.5%, 42.0% and 35.1%, respectively) than that in the group with t<92 s, EOD<5% and ΔP ≥ 55 beats/min (16.9%, 21.5% and 18.2%, respectively). Binary logistic regression analysis showed that postoperative cardiopulmonary complications were independently correlated with EOD and lung function which did not meet the requirement of the lung resection operation mode.</p><p><b>CONCLUSIONS</b>A symptom-limited stair climbing test is a safe, simple and low-cost method to evaluate the cardiopulmonary function preoperatively. It can predict the occurrence of postoperative cardiopulmonary complications in non-small cell lung cancer patients. Conventional pulmonary function tests and stair-climbing test can be recommended to be routinely performed in all patients with non-small cell lung cancer before thoracic surgery.</p>

Simultaneous determination of human plasma protein binding of bioactive flavonoids in Polygonum orientale by equilibrium dialysis combined with UPLC-MS/MS / 药物分析学报

A simple and selective ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) assay was developed for the determination of the human plasma protein binding of four bioactive flavonoids (such as orientin and vitexin) in Polygonum orientale. Protein precipitation was used for sample preparation. Equilibrium dialysis technique was applied to determine the plasma protein binding under physiological conditions. The separation was achieved through a Waters C18 column with a mobile phase composed of 0.1%formic acid in acetonitrile and 0.1%aqueous formic acid using step gradient elution at a flow rate of 0.35 mL/min. A Waters ACQUITY?TQD system was operated under the multiple reaction monitoring (MRM) mode of positive electrospray ionization. All of the recovery, precision, accuracy and stability of the method met the requirements. Good correlations (r40.99) of the four compounds were found, which suggested that these compounds can be simultaneously determined with acceptable accuracy. Results showed that the plasma protein bindings of the four bioactive flavonoids were in the range of 74-89% over the six concentrations studied. The binding parameters containing protein binding affinity, protein binding dissociation constant, and protein binding site were studied. The maximum ability to bind with protein was also determined in the assay in order to understand the drug-protein binding of each compound better.

The complexes of adenovirus and anionic liposomes: preparation and in vitro characterization / 药学学报

This study is to report the preparation of complexes of Ad5 and anionic liposomes (AL-Ad5), the amplification of adenoviruses with enhanced green fluorescent protein (eGFP) reporter gene performed by HEK 293 cells, the adenoviral vectors purified by cesium chloride gradient centrifugation, and the titer of adenovirus determined by cytopathic effect (CPE) method, hexon capsid immunoassay and quantitative-PCR (Q-PCR), separately. The prescription and experiment conditions were optimized by central composite design (CCD). The complexes of Ad5 and AL-Ad5 were formulated by the calcium-induced phase change method. The morpholopy, particle size and zeta potential were detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. Additionally, the bicolourable fluoresce-labeled complexes (F(labeled)-AL-Ad5) were prepared and their intracellular location in MDCK cells was detected by confocal laser scanning microscopy (CLSM). The results indicate that the complexes of AL-Ad5 exhibited a uniform distribution with a particle size of 211 +/- 10 nm and a zeta potential of -41.2 +/- 2.2 mV. The result of CLSM demonstrates that the intracellular location of red fluoresce-labeled adenovirus was consistent with that of green fluoresce-labeled liposomes suggesting that the naked adenovirus was well encapsulated by the anionic liposomes in complexes of AL-Ad5.