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Objective: This study aims to explore the temporal trend of Low Anterior Resection Syndrome (LARS) and its symptoms after laparoscopic anterior resection for rectal cancer. Methods: A retrospective cohort study design was employed. The study included primary rectal (adenocarcinoma) cancer patients who underwent laparoscopic anterior resection at Tongji Hospital, Huazhong University of Science and Technology, between January 1, 2010, and December 31, 2020. Complete medical records and follow-up data at 3, 6, 9, 12, and 18 months postoperatively were available for all patients. A total of 1454 patients were included, of whom 1094 (75.2%) were aged ≤65 years, and 597 (41.1%) were females. Among them, 1040 cases (71.5%) had an anastomosis-to-anus distance of 0-5cm, and 86 cases (5.9%) received neoadjuvant treatment. All patients completed the Chinese version of the LARS questionnaire and their LARS occurrence and specific symptom information were recorded at 3, 6, 9, 12, and 18 months postoperatively. Considering past literature and clinical experience, further subgroup analyses were performed to explore the potential impact factors on severe LARS, including anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma. Results: The occurrence rates of LARS at 3, 6, 9, 12, and 18 months postoperatively were 78.5% (1142/1454), 71.4% (1038/1454), 55.0% (799/1454), 45.7% (664/1454), and 45.7% (664/1454), respectively (χ 2 =546.180 , P <0.001). No statistically significant difference was observed between the 12-month and 18-month time points ( P >0.05). When compared with the symptoms at 3 months, the occurrence rates of gas incontinence [1.7% (24/1454) vs. 33.9% (493/1454)], liquid stool incontinence [3.9% (56/1454) vs. 41.9% (609/1454)], increased stool frequency [79.6% (1158/1454) vs. 95.9% (1395/1454)], stool clustering [74.3% (1081/1454) vs. 92.9% (1351/1454)], and stool urgency [46.5% (676/1454) vs. 78.7% (1144/1454)] in the LARS symptom spectrum were significantly alleviated at 12 months (all P <0.05) and remained stable beyond 12 months (all P >0.05). With the extension of postoperative time, the incidence rates of severe LARS exhibited a decreasing trend in different subgroups, of anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma, and reached stability at 12 months postoperatively (all P >0.05). Conclusion: LARS and its specific symptom profile showed a trend of gradual improvement over time up to 1 year postoperatively, and stabilized after more than 1 year. Increased stool frequency and stool clustering are the most common features of abnormal bowel dys function, which improve slowly after surgery.

We evaluated the effects of supplementing bacterial direct-fed microbial (DFM) on performance, apparent total-tract digestibility, rumen fermentation, and immune parameters of lactating dairy cows. One hundred fourteen multiparous Holstein cows (41 ± 7 DIM) were used in a randomized complete block design with an experiment comprising 14 d of a covariate (pre-experimental sample and data collection) and 91 d of an experimental period. Cows were blocked based on energy-corrected milk (ECM) yield during the covariate period and the following treatments were randomly assigned within each block: (1) control (CON), corn silage-based total mixed ration without DFM; (2) PRO-A, basal diet top-dressed with a mixture of Lactobacillus animalis and Propionibacterium freudenreichii at 3 × 10 9 cfu/d; and 3) PRO-B, basal diet top-dressed with a mixture of L. animalis, P. freudenreichii, Bacillus subtilis, and Bacillus licheniformis at 11.8 × 10 9 cfu/d. Milk yield, dry matter intake (DMI), and body weight were measured daily, while milk samples for component analysis were taken on 2 consecutive days of each week of data collection. Feces, urine, rumen, and blood samples were taken during the covariate period, wk 4, 7, 10, and 13 for estimation of digestibility, N-partitioning, rumen fermentation, plasma nutrient status and immune parameters. Treatments had no effect on DMI and milk yield. Fat-corrected milk (3.5% FCM) and milk fat yield were improved with PRO-B, while milk fat percent and feed efficiency (ECM/DMI) tended to increase with PRO-B compared with PRO-A and CON. Crude fat digestibility was greater with PRO-B compared with CON. Feeding CON and PRO-A resulted in higher total volatile fatty acid concentration relative to PRO-B. Percentage of neutrophils tended to be reduced with PRO-A compared with CON and PRO-B. The mean fluorescence intensity (MFI) of anti-CD44 antibody on granulocytes tended to be higher in PRO-B compared with CON. The MFI of anti-CD62L antibody on CD8+ T cells was lower in PRO-A than PRO-B, with PRO-A also showing a tendency to be lower than CON. This study indicates the potential of DFM to improve fat digestibility with consequential improvement in fat corrected milk yield, feed efficiency and milk fat yield by lactating dairy cows. The study findings also indicate that dietary supplementation with DFM may augment immune parameters or activation of immune cells, including granulocytes and T cells; however, the overall effects on immune parameters are inconclusive., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Hypothesis: Horseshoe vortices are known to emerge around large-scale obstacles, such as bridge pillars, due to an inertia-driven adverse pressure gradient forming on the upstream-side of the obstacle. We contend that a similar flow structure can arise in thin-film Stokes flow around micro-obstacles, such as used in textured surfaces to improve wettability. This could be exploited to enhance mixing in microfluidic devices, typically limited to creeping-flow regimes., Experiments: Numerical simulations based on the Navier-Stokes equations are carried out to elucidate the flow structure associated with the wetting dynamics of a liquid film spreading around a 50 μm diameter micro-pillar. The employed multiphase solver, which is based on the volume of fluid method, accurately reproduces the wetting dynamics observed in current and previous (Mu et al., Langmuir, 2019) experiments., Findings: The flow structure within the liquid meniscus forming at the foot of the micro-pillar evinces a horseshoe vortex wrapping around the obstacle, notwithstanding that the Reynolds number in our system is extremely low. Here, the adverse pressure gradient driving flow reversal near the bounding wall is caused by capillarity instead of inertia. The horseshoe vortex is entangled with other vortical structures, leading to an intricate flow system with high-potential mixing capabilities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function ( P =0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Background: The objective was to determine how molasses and Lactobacillus plantarum affect chemical composition, fermentation quality, aerobic stability, and the microbial community of an ensiled mixture of amaranth (Amaranthus hypochondriaus, AF) and rice straw. Treatments were control (C, no addition), L. plantarum (L; 2 × 10 5  cfu g -1 fresh weight), molasses (M; 40 g kg -1 fresh matter), and their combination (LM). All treatments were ensiled for 1, 3, 5, 7, and 30 days., Results: All additives improved fermentation quality with greater lactic acid (LA), acetic acid, and lower pH than C silage over the ensiling period. The LM silage combination optimized fermentability, manifested as greater LA contents and a more rapid pH reduction during the first 7 days of ensiling than L or M silages. After 30 days of ensiling, inoculant L. plantarum increased Lactobacillus abundance and reduced bacterial diversity and Enterobacteriaceae abundance compared with silage treated with molasses. Molasses addition reduced the relative concentration of structural carbohydrates (neutral and acid detergent fiber, and hemicellulose) after 30 days of ensiling. Finally, there was spoilage after 2 days and 4 days of aerobic exposure in C and LM silages respectively, whereas L silage had not spoiled after 4 days., Conclusions: Although the combination of L. plantarum and molasses further optimized fermentation characteristics, L silage had better aerobic stability. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

The neutral particles generated by charge exchange reactions can play an important role in erosion of first wall materials in fusion devices. In order to measure the flux and energy of neutral particles to the first wall, a low-energy neutral particle analyzer (LENPA) based on the time-of-flight method has been developed and successfully applied on the Experimental Advanced Superconducting Tokamak (EAST)' to measure the neutrals with an energy of 20-3000 eV. The LENPA works in the counting mode, and the signal of photons is used as the reference for the flight time of neutrals. The energy spectrum of low-energy neutral particles on EAST has been obtained for the first time. The new diagnostics can help in understanding the neutral particle generation and deposition on the first wall materials in tokamaks under different plasma conditions.

This study aimed to examine the effect of eicosapentaenoic acid (EPA) on skeletal muscle hypertrophy induced by muscle overload and the associated intracellular signaling pathways. Male C57BL/6J mice were randomly assigned to oral treatment with either EPA or corn oil for 6 weeks. After 4 weeks of treatment, the gastrocnemius muscle of the right hindlimb was surgically removed to overload the plantaris and soleus muscles for 1 or 2 weeks. We examined the effect of EPA on the signaling pathway associated with protein synthesis using the soleus muscles. According to our analysis of the compensatory muscle growth, EPA administration enhanced hypertrophy of the soleus muscle but not hypertrophy of the plantaris muscle. Nevertheless, EPA administration did not enhance the expression or phosphorylation of Akt, mechanistic target of rapamycin (mTOR), or S6 kinase (S6K) in the soleus muscle. In conclusion, EPA enhances skeletal muscle hypertrophy, which can be independent of changes in the AKT-mTOR-S6K pathway.

A quartz crystal microbalance (QMB) diagnostic system has been established in Experimental Advanced Superconducting Tokamak (EAST) for real-time and in situ measurements of erosion and deposition rates of plasma-facing materials at the first wall. A ∼70 nm aluminum (Al) film has been coated on the QMB crystal surface to measure the erosion rate by charge exchange neutral particles. Dual sensors of the QMB system have been used with a closed sensor for reference. The stability and light sensitivity of the QMB system have been tested in the lab, demonstrating its feasibility on the application of EAST experiments. The QMB system with cooling water has been successfully applied in the 2018 EAST campaign. The net erosion thickness measured by the QMB has been well validated by thickness measurements using the Rutherford backscattering spectrometry. The developed QMB systems can help us to understand the physics processes of material erosion and deposition at main chamber walls for long pulse operations in EAST.

Objective: To explore the clinical effect of nutritional and psychological intervention combined with pulmonary rehabilitation exercise on patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 260 patients with COPD admitted to the Sixth Affiliated Hospital of Kunming Medical University from October 2014 to October 2017 were included. They were divided into mild, moderate, severe and extremely severe groups according to forced expiratory volume in one second predicted (FEV(1)%prep) of pulmonary function. The patients were divided into control group and comprehensive management group according to the random number table method. The control group was given routine treatment including smoking quitting persuasion, vaccination, oxygen therapy and standardized medication. The comprehensive management group was given additional nutritional support, psychological intervention and pulmonary rehabilitation exercise. The data of the lung function indexes (FEV(1)%prep, FEV(1)/FVC, PaO(2), PaCO(2)), nutritional indexes [body mass index (BMI), albumin (ALB), nutrition risk screening (NRS)2002], anxiety and depression scores, 6-minute walking distance (6MWD), modified medical research council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George's score, and frequency of acute exacerbations were compared between two groups after 12 months of treatment. Results: After 12 months' treatment, PaO(2) in the comprehensive management group was significantly higher than that in the control group [(51.1±7.2) vs (47.0±9.1) mmHg] (1 mmHg=0.133 kPa); Nutritional risk (NRS2002) decreased obviously [(1.1±1.1) vs (2.2±1.0)]; anxiety score [(4.1±2.2) vs (5.6±2.7)]; depression score [(4.1±2.0) vs (5.5±2.6)] and St. George's score [(36.8±20.8) vs (48.6±19.5)] decreased significantly ( P< 0.05). And the 6MWD was significantly farther [(368.4±72.0) vs (343.4±75.0) m] in management group. The frequency of acute exacerbations was significantly reduced in the mild, moderate and severe groups ( P< 0.05). But there was no significant difference in FEV(1)%prep, FEV(1)/FVC, PaCO(2), BMI, ALB, mMRC score and CAT score. Conclusion: Nutritional and psychological intervention combined with pulmonary rehabilitation exercise can reduce the nutritional risk and the frequency of acute exacerbations in patients with COPD, relieve anxiety and depression state and improve the quality of life.

Objective: To evaluate the feasibility and effectiveness of the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis in the treatment of upper urinary tract urothelial carcinoma (UTUC), and to review the experience of renal autotransplantation for UTUC treatment., Methods: One case of applying the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis to the UTUC treatment was reported, and related literature was reviewed. The patient was a sixty-four-year old man who received right radical nephroureterectomy for right ureteral carcinoma 1 year before and diagnosed as left ureteral carcinoma(G2, high grade) this time. In order to preserve his renal function and avoid the shortness of common kidney-sparing surgery, a totally extraperitoneal procedure, including retroperitoneoscopic nephrectomy, ureterectomy, renal autotransplantation and Boari flap-pelvis anastomosis, was performed to the patient., Results: The operation was completed successfully without perioperative complications. The renal function recovered to preoperative level within 1 week. No deterioration of renal function during the follow-up and no tumor recurrence was observed under cystoscopy at the 3-month postoperative consult., Conclusion: The totally extraperitoneal renal autotransplantation with Boari flap-pelvis anastomosis is a feasible and effective treatment for UTUC. The innovative procedure has several advantages compared to the former ones. The extraperitoneal procedure results in significantly less pain, shorter hospital stay, decreased overall time to recovery and lower bowel complications risk without warm ischemia time extension. Meanwhile, the Boari flap-pelvis anastomosis simplifies the follow -up protocols and creates an easy route for cystoscopy and topical therapy. From the systematic clinical analysis, as well as the related literature review, it's been concluded that the renal autotransplantation can be a reasonable option for the patients who have UTUC in solitary kidney or have bilateral UTUC. This type of treatment possesses advantages of preservation of renal function and total resection of malignant lesions. But long-term data and large cohort study on renal function or tumor recurrence are still absent which will be necessary to confirm the advantages of this approach.

Purpose: The effects of adipose insulin resistance on cardiovascular risk factors in polycystic ovary syndrome (PCOS) remain largely unknown. We aimed to investigate associations between adipose insulin resistance and cardiovascular risk factors in PCOS., Methods: A total of 207 PCOS and 47 non-PCOS women were recruited from a large reproductive medicine center in this cross-sectional study. The PCOS diagnosis was based on the Rotterdam Criteria. The subjects received a standard oral glucose tolerance test. Adipose insulin resistance was evaluated using a validated index (adipose-IR = fasting insulin × free fatty acid concentrations)., Results: The women with PCOS showed a higher adipose-IR index, and the adipose-IR index was tightly associated with the blood pressure, glucose and lipid parameters. A total of 98.0% of the women with PCOS in the highest adipose-IR quartile showed cardiovascular risk factors (obesity, hypertension, glucose intolerance or dyslipidemia), and this percentage was significantly higher than the percentage of those in the lowest quartile (32.7%). In addition, the percentages of women with three (31.4%) and four (13.7%) cardiovascular risk factors were significantly elevated in the highest adipose-IR quartile. The multivariable logistic regression analysis indicated that each 1-SD increment in the adipose-IR index resulted in higher risks of obesity (OR = 3.18, 95% CI = 2.12-4.76), hypertension (OR = 1.89, 95% CI = 1.31-2.73), glucose intolerance (OR = 2.45, 95% CI = 1.73-3.48), and dyslipidemia (OR = 2.18, 95% CI = 1.57-3.01). The C-reactive protein (CRP) level was positively associated with the adipose-IR index in women with PCOS (r = 0.45, P < 0.001)., Conclusions: The adipose-IR index was associated with cardiovascular risk factors in women with PCOS. Chronic inflammation may induce insulin resistance in the adipose tissue of women with PCOS.

Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.

To understand the erosion effect of neutral particles on the first wall, a low energy neutral particle analyzer (LENPA), based on the time-of-flight method, has been developed for the Experimental Advanced Superconducting Tokamak (EAST). The LENPA to be installed in the EAST mid-plane mainly consists of a chopper sub-system, a 3 m long flight tube, two sets of detector assemblies, and data acquisition and processing, vacuum, power supply, and control sub-systems. The neutral outflux is gated in bunches of 1 μ s time scale by a slotted rotating disc which is driven by a vacuum compatible motor modified from a turbomolecular pump. A He-Ne laser beam is projected through the disc slit to record the instants of chopper slits opening with an avalanche photodiode module. An on-axis electron multiplier detects chopped neutrals, and a central perforated Cu-Be plate is employed to channel the emitted secondary electrons into an off-axis electron multiplier. The radiation peaks of on-axis electron multiplier caused by UV photons projected through the central hole of the Cu-Be plate provide an alternative way to record the chopper slits' opening time. With an additional 4 TB fast memory card, 1 GS/s sampling rate has been realized by using a GaGe acquisition card continuously. The LENPA data from the EAST together with neutral particle material erosion experiments will be used to benchmark the simulation results for better predictions on future fusion reactors, such as ITER and China Fusion Engineering Test Reactor (CFETR).

Objectives To investigate the mortality and causes of death in Chinese patients with systemic lupus erythematosus. Methods We collected the clinical data of all consecutive adult systemic lupus erythematosus patients at the Rheumatology department of Peking University First Hospital between January 2007 and December 2015. The primary causes of death were identified, the standardized mortality ratio and years of life lost were calculated, and the survival and variables associated with mortality were determined by Kaplan-Meier and Cox regression analysis respectively. Results The mean age of all 911 patients (814 females and 97 males) was 37.8 ± 14.7 years, the median disease duration at recruitment was 2.6 (0.5-7.0) years, and the median follow-up duration was 3.0 (1.4-5.1) years. Among the 911 patients who were successfully followed up, 45 patients died. Infection (31.1%) was the leading cause of death followed by renal failure, pulmonary arterial hypertension and cerebrovascular diseases. The overall age and sex-adjusted standardized mortality ratio was 3.2 (95% confidence interval 2.4-4.0), and the years of life lost for women and men were 29.8 and 9.4 respectively. Overall survival at 1, 5 and 10 years was 98.2%, 95.3% and 93.7% respectively. Older age at disease onset, infection, autoimmune hemolytic anemia, thrombocytopenia and pulmonary arterial hypertension were independent risk factors for the mortality of systemic lupus erythematosus patients, and longer disease duration at recruitment was an independent protective factor. Conclusions Mortality of systemic lupus erythematosus patients in China was substantial, especially in females, with infection the leading cause of death. Older age at disease onset, infection, autoimmune hemolytic anemia, thrombocytopenia and pulmonary arterial hypertension were associated with poor outcomes.

Objective: To analyze the relationship between the breast cancer molecular classification and the prognosis of patients underwent breast-conserving therapy and to discuss the safety of the breast conserving surgery from the choice of operation in terms of breast cancer molecular classification. Methods: Clinical data of 618 patients with breast-conserving therapy in Tianjin Medical University Cancer Institute and Hospital from August 2005 to August 2010 were analyzed retrospectively. According to the molecular classification when breast cancer was diagnosed, patients were subdivided into five groups, including Luminal A, Luminal B1, Luminal B2, HER-2-positive and Triple-negative. Clinicopathological characteristics and prognosis were compared among five groups and the influencing factors of local recurrence, distant metastasis and overall survival were analyzed. Results: Among 618 patients, there were 148 cases Luminal A, 231 cases Luminal B1, 63 cases Luminal B2, 40 cases HER-2-positive and 136 cases Triple-negative. The age, family history, TNM stage, calcification, histological grade, pathological type and response to endocrine therapy of these 5 molecular types of breast cancer patients were significantly different (all P <0.05). The 5-year local regional recurrence-free survival rates of Luminal A, Luminal B1, Luminal B2, HER-2-positive and Triple-negative were 99.3%, 98.7%, 98.4%, 94.9% and 95.9%, respectively, without significant differences ( P =0.104). The 5-year distant metastasis-free survival rates of these 5 types were 97.3%, 95.7%, 93.7%, 87.5% and 91.4%, respectively, with significant differences ( P =0.013). Moreover, the 5-year overall survival rates of these 5 types were 98.6%, 97.8%, 98.4%, 92.5% and 95.6%, respectively, without significant differences ( P =0.153). Multifactor analysis showed that radiotherapy ( HR =0.036, P =0.049) and the number of lymph node metastases ( HR =10.72, P =0.004) were independent factors of local recurrence of breast cancer patients underwent breast-conserving therapy. The age ( HR =0.369, P =0.046), status of surgical margin ( HR =5.486, P =0.007), number of lymph node metastases ( HR =2.882, P =0.023) and molecular typing ( HR =5.191, P =0.008) were independent factors of distant metastasis of above breast cancer patients. None of the factors were found to be independent factors of the overall survival of these breast cancer patients. Conclusions: Breast conserving therapy does not increase the risks of local recurrence and death of HER-2-positive and Triple-negative breast cancer patients. Therefore, breast conserving therapy can be accepted by patients with HER-2-positive and Triple-negative breast cancer.

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Sex hormone receptors play critical roles in development and reproduction. However, it is not known whether they exist in Raillietina tapeworms, and if they do, whether they have a similar function to that in vertebrates. We examined the immunohistochemical distributions of androgen receptors (ARs), estrogen receptors (ERs), and progesterone receptors (PRs) in the tissues of two tapeworm species: Raillietina echinobothrida and Raillietina tetragona. Immunopositive ARs were found in the entire reproductive system of R. echinobothrida, including the testes, ovaries, and oocysts, and weakly immunopositive ERs and PRs were found in the testes, ovaries, and oocysts. Immunopositive ARs were also found throughout the entire reproductive system of R. tetragona, including the testes, ovaries, and oocysts, and weakly immunopositive ERs were in the testes and oocysts; the PRs were distributed in an immunonegative manner. The results show that androgens and their receptors play critical roles in reproductive system development in the two tapeworms. The immunoreactivity and tissue localizations of the sex hormone receptors suggest that, in both species, they have similar functions as in vertebrates, and modulate reproduction.

Objective: To explore the impact of immediate breast reconstruction on the onset of adjuvant chemotherapy and on the postoperative complications. Methods: We retrospectively analyzed the clinical data from female breast cancer patients treated by either modified radical mastectomy with immediate breast reconstruction(IBR) ( n =108) or modified radical mastectomy alone( n =115), followed by adjuvant chemotherapy at our department between January 2011 and December 2012. Results: There was no significant difference in the overall complication rates between the IBR group and modified radical mastectomy group (49.1% vs. 52.2%, P =0.87). However, more secondary surgery was applied in the IBR group than the modified radical mastectomy group (13.0% vs. 1.7%, P =0.001). However, the incidence of hematoma in the modified radical mastectomy group was significantly higher than the IBR group (17.4% vs. 4.6%, P =0.003). There was a significant difference in the onset of adjuvant chemotherapy between the IBR group and modified radical mastectomy group (21 days vs. 11days, P <0.001). Conclusions: Immediate breast reconstruction has no significant impact on the overall complication rate, but increases the incidence of secondary surgery, especially after the initiation of chemotherapy. In addition, it slightly delays adjuvant chemotherapy in the patients.

The search for novel image contrasts has been a major driving force in the magnetic resonance (MR) research community, in order to gain further information on the body's physiological and pathological conditions.Chemical exchange saturation transfer (CEST) is a novel MR technique that enables imaging certain compounds at concentrations that are too low to impact the contrast of standard MR imaging and too low to directly be detected in MRS at typical water imaging resolution. For this to be possible, the target compound must be capable of exchanging protons with the surrounding water molecules. This property can be exploited to cause a continuous buildup of magnetic saturation of water, leading to greatly enhanced sensitivity.The goal of the present review is to introduce the basic principles of CEST imaging to the general molecular imaging community. Special focus has been given to the comparison of state-of-the-art CEST methods reported in the literature with their positron emission tomography (PET) counterparts.

The aim of this study was to investigate the abilities of cartilage-derived morphogenetic protein 1 (CDMP1) transgenic cell sheets in repairing rabbit cartilage defects. Rabbit CDMP1 transgenic bone marrow mesenchymal stem cell (BMSC) sheets (CDMP1-BMSCs) were cultured on temperature-sensitive culture dishes, and CDMP1 expression and type II collagen protein in the cell sheets were detected. Tissue-engineered cell sheets were constructed and transplanted into defect rabbit thyroid cartilage, to investigate the expression of engineered cartilage collagen protein and proteoglycan (GAG). The experiment was divided into three groups; A) BMSC sheet, B) Ad-CMV-eGFP-transfected cell sheet, and C) Ad-CMV-hCDMP1-IRES-eGFP-transfected cell sheet. The expression of CDMP1 was detected in the transgenic cell sheets. The engineered cartilage exhibited positive immunohistochemical and Alcian blue staining. The expression levels of type II collagen protein and GAG in group A were positive, whereas those in group B and group C were negative (P < 0.05). The CDMP1-BMSC sheets had a good cartilage differentiation activity, and could effectively repair rabbit laryngeal cartilage defects.

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Worldwide, water scarcity threatens delivery of water to urban centers. Increasing water use efficiency (WUE) is often recommended to reduce water demand, especially in water-scarce areas. In this paper, agricultural water use efficiency (AWUE) is examined using the super-efficient data envelopment analysis (DEA) approach in Xi'an in Northwest China at a temporal and spatial level. The grey systems analysis technique was then adopted to identify the factors that influenced the efficiency differentials under the shortage of water resources. From the perspective of temporal scales, the AWUE increased year by year during 2004-2012, and the highest (2.05) was obtained in 2009. Additionally, the AWUE was the best in the urban area at the spatial scale. Moreover, the key influencing factors of the AWUE are the financial situations and agricultural water-saving technology. Finally, we identified several knowledge gaps and proposed water-saving strategies for increasing AWUE and reducing its water demand by: (1) improving irrigation practices (timing and amounts) based on compatible water-saving techniques; (2) maximizing regional WUE by managing water resources and allocation at regional scales as well as enhancing coordination among Chinese water governance institutes.

Epileptogenesis is a dynamic process initiated by insults to the brain that is characterized by progressive functional and structural alterations in certain cerebral regions, leading to the appearance of spontaneous recurrent seizures. Within the duration of the trauma to the brain and the appearance of spontaneous recurrent seizures, there is typically a latent period, which may offer a therapeutic window for preventing the emergence of epilepsy. Previous animal studies have shown that curcumin can attenuate acute seizure severity and brain oxidative stress, but the effect of curcumin on epileptogenesis has not been studied. We examined the effect of continued administration of curcumin during the latent period on epileptogenesis and the deleterious consequences of status epilepticus in adult rats in a post-status epilepticus model of temporal lobe epilepsy induced by kainic acid. We demonstrate that, while administration of curcumin treatment during the latent period does not prevent occurrence of spontaneous recurrent seizures after status epilepticus, it can attenuate the severity of spontaneous recurrent seizures and protect against cognitive impairment. Thus, treatment with curcumin during the latent period following status epilepticus is beneficial in modifying epileptogenesis., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Epidermal growth factor receptor (EGFR) signaling regulates cell growth and survival, and its overactivation drives cancer development. One important branch of EGFR signaling is through activation of GTPase Rac1, which further promotes cell proliferation, survival and cancer metastasis. Here, we show that EGFR activates Rac1 via inducing the accumulation of its specific guanine nucleotide exchange factor, T-cell lymphoma invasion and metastasis 1 (Tiam1) in non-small-cell lung cancer and colon cancer cells. Conversely, elevated Tiam1 is required for EGFR-induced tumorigenesis. In human lung adenocarcinoma and colon cancer specimens, Tiam1 expression strongly correlates with EGFR expression. We further reveal that AKT, a key downstream protein kinase of EGFR, phosphorylates Tiam1 at several consensus sites, facilitates the interaction of Tiam1 with scaffold proteins 14-3-3 and leads to an increase of Tiam1 stability. Subsequently, Tiam1 is dephosporylated and destabilized by PP2A. Together, our study identifies a bidirectional (phosphorylation and dephosphorylation) regulatory mechanism controlling Tiam1 stability and provides new insights on how EGFR signaling triggers Rac1 activation and cancer development.

Parkinsons Disease (PD) is a neurodegenerative disorder of the dopaminergic neurons in the substantia nigra. Much of the scientific literature on the Parkinson's disease has been focused on the evaluation and management of motor conditions in PD. Much less stress has been laid on evaluating and managing the cognitive disturbances found comorbidly in this condition. Studies have suggested that the cognitive dysfunction observed in PD can range anywhere from individual cognitive deficits to the clinical picture of minimal cognitive impairment to as much as a full-blown dementia like clinical picture. Perhaps because of this poor understanding, the treatments for this comorbidity have not been able to be adequately developed. Right now, only rivastigmine is the approved drug of choice for treatment of dementia associated with PD. In this review we aim at elaborating the individual cognitive deficits associated with PD instead of focusing on full-blown dementia. Our aim at focusing on individual symptoms is important because these symptoms should be evaluated even at the most beginning stages of PD rather than waiting for the patient to report for the symptoms. Therefore, we will aim at elaborating the prevalence, symptomatology and implications for treatment for these cognitive dysfunctions individually. Because covering all the domains of cognitive dysfunctions are not possible here, we will focus on three cognitive impairments which are most commonly observed in the PD patients. These are the (1) Executive function deficits (2) Memory deficits and (3) visuospatial deficits. We will, finally, have an overview of the condition of minimal cognitive deficits observed in PD.

FoxN1 is cell-autonomously expressed in skin and thymic epithelial cells (TECs), essential for their development. Inborn mutation of FoxN1 results in hair follicle and TEC development failure, whereas insufficient postnatal FoxN1 expression induces thymic atrophy, resulting in declined T lymphopoiesis. Although upregulating FoxN1 expression in the aged FoxN1-declined thymus rejuvenates T lymphopoiesis, whether its over- and ectopic-expression in early life is beneficial for T lymphopoiesis is unknown. Using our newly generated Rosa26-STOP(flox)-FoxN1 mice, in which over- and ectopic-expression of FoxN1 can be induced by various promoter-driven Cre-mediated deletions of the roadblock STOP(flox) in early life, we found that K14Cre-mediated inborn FoxN1 overexpression induced neonatal lethality, exhibited abnormal permeability in the skin and abnormal nursing. Ubiquitous deletion of the STOP(flox) mediated by progressive uCreER(T) leakage in juvenile mice affected thymus and bone marrow normality, resulting in an increased ratio of medullary/cortical TECs, along with declined T and B lymphopoiesis. Although the K5CreER(T)-mediated FoxN1 overexpression mice had a normal lifespan, induction of K5CreER(T) activation in juveniles adversely influenced total thymoycte development and produced ichthyosis-like skin. Therefore, FoxN1 has temporal and tissue-specific activity. Over- and ectopic-expression of FoxN1 in early life adversely influence immature TEC, T and B cell, and skin epithelial development.

Periodontitis is a common chronic inflammatory disease initiated by bacteria, resulting in bone resorption, tooth loss, and systemic inflammation. Long-chain omega-3 fatty acids such as docosahexaenoic acid (DHA) reduce periodontitis in animals. We aimed to determine whether DHA supplementation with low-dose aspirin would reduce periodontitis in humans. We conducted a double-blind placebo-controlled parallel trial lasting 3 mo. Fifty-five adults with moderate periodontitis were randomized to 2,000 mg of DHA or identical soy/corn oil capsules. All participants received 81 mg of aspirin but received no other treatments. We analyzed the primary outcome of per-pocket change in pocket depth using mixed models among teeth with pocket depth ≥5 mm. Secondary outcomes assessed with generalized estimating equations included gingival index, plaque index, and bleeding on probing. Gingival crevicular fluid samples were analyzed for changes in high-sensitivity C-reactive protein (hsCRP) and interleukins 6 and 1β (IL-6 and IL-1β). Plasma was analyzed for changes in systemic inflammatory markers, including hsCRP. We confirmed adherence with erythrocyte fatty acid measurement. Forty-six participants completed the trial. While similar at baseline, the proportion of DHA in red blood cell plasma membranes increased from 3.6% ± 0.9% to 6.2% ± 1.6% in the intervention group but did not change among controls. DHA supplementation decreased mean pocket depth (-0.29 ± 0.13; p = .03) and gingival index (-0.26 ± 0.13; p = .04). Plaque index and bleeding on probing did not change. Significant adjusted differences were found between DHA and control for both gingival crevicular fluid hsCRP (-5.3 ng/mL, standard error [SE] = 2.4, p = .03) and IL-1β (-20.1 pg/mL, SE = 8.2, p = .02) but not IL-6 (0.02 pg/mL, SE = 0.71, p = .98) or systemic hsCRP (-1.19 mg/L, SE = 0.90, p = .20). In this randomized controlled trial, aspirin-triggered DHA supplementation significantly improved periodontal outcomes in people with periodontitis, indicating its potential therapeutic efficacy (clinicaltrials.gov NCT01976806)., (© International & American Associations for Dental Research.)

Reasons for Performing Study: As part of investigation into laryngeal stability and reanimation using functional electrical stimulation, the cricothyroid muscle might be utilised to increase laryngeal cross-sectional area in horses with recurrent laryngeal neuropathy. For optimal electrode placement and muscle recruitment, the neuroanatomy and excitability of the equine cricothyroid muscle needs to be defined., Objectives: To describe the anatomy, innervation and function of the equine cricothyroid muscle and its contribution to laryngeal diameter., Methods: Seventeen equine larynges were collected at necropsy and 12 were grossly dissected. Seven larynges (five grade 1, two grade 4) were prepared for immunohistochemistry following gross dissection and 5 larynges were prepared for special staining: acetylcholinesterase staining of motor endplates (n = 3) and Sihler's staining (n = 2). Three larynges were stimulated following in situ cadaver dissection and 2 larynges were removed and stimulated ex vivo., Results: Three neuromuscular compartments, each innervated by a primary nerve branch of the external branch of the cranial laryngeal nerve, were identified in all larynges. Stimulation of each neuromuscular compartment resulted in ventral displacement of the thyroid cartilage with respect to the cricoid cartilage, thereby increasing dorsoventral height of the rima glottis., Conclusions: The equine cricothyroid muscle has 3 distinct neuromuscular compartments with discrete innervation, fibre type distribution and muscle fibre sizes. All neuromuscular compartments tense the vocal cords by increasing dorsoventral height of the rima glottis through ventral displacement of the thyroid cartilage with respect to the cricoid cartilage., Potential Relevance: Simultaneous functional electrical stimulation of the cricothyroid and dorsal cricoarytenoid muscles may enhance laryngeal cross-sectional area in horses with recurrent laryngeal neuropathy., (© 2012 EVJ Ltd.)

Glutamate is the major mediator of excitotoxic neuronal death following cerebral ischemia. Under severe ischemic conditions, glutamate transporters can functionally reverse to release glutamate, thereby inducing further neuronal injury. Hypothermia has been shown to protect neurons from brain ischemia. However, the mechanism(s) involved remain unclear. Therefore, the aim of this study was to investigate the mechanism(s) mediating glutamate release during brain ischemia-reperfusion injury under hypothermic conditions. Neuron/astrocyte co-cultures were exposed to oxygen-glucose deprivation (OGD) at various temperatures for 2h, and cell viability was assayed 12h after reoxygenation. PI and MAP-2 staining demonstrated that hypothermia significantly decreased neuronal injury. Furthermore, [(3)H]-glutamate uptake assays showed that hypothermia protected rat primary cortical cultures against OGD reoxygenation-induced injury. Protein levels of the astrocytic glutamate transporter, GLT-1, which is primarily responsible for the clearance of extracellular glutamate, were also found to be reduced in a temperature-dependent manner. In contrast, expression of GLT-1 in astrocyte-enriched cultures was found to significantly increase following the addition of neuron-conditioned medium maintained at 37 °C, and to a lesser extent with neuron-conditioned medium at 33 °C. In conclusion, the neuroprotective effects of hypothermia against brain ischemia-reperfusion injury involve down-regulation of astrocytic GLT-1, which mediates the reverse transport of glutamate. Moreover, this process may be regulated by molecules secreted by stressed neurons., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

The utility of multivariate analysis in in vitro metabolite identification studies was examined with nefazodone, an antidepressant drug with a well-established metabolic profile. The chromatographic conditions were purposefully chosen to reflect those utilized in high-throughput screening for microsomal stability of new chemical entities. Molecular ion, retention time information on groups of human liver microsomal samples with/without nefazodone was evaluated by principal component analysis (PCA). Resultant scores and loadings plots from the PCA revealed the segregation and the ions of interest that designated the drug and its corresponding metabolites. Subsequent acquisition of tandem mass spectrometry (MS/MS) spectra for targeted ions permitted the interrogation and interpretation of spectra to identify nefazodone and its metabolites. A comparison of nefazodone metabolites identified by PCA versus those found by traditional metabolite identification approaches resulted in very good correlation when utilizing similar analytical methods. Fifteen metabolites of nefazodone were identified in beta-nicotinamide adenine dinucleotide phosphate (NADPH)-supplemented human liver microsomal incubations, representing nearly all primary metabolites previously reported. Of the 15 metabolites, eight were derived from the N-dealkylation and N-dephenylation of the N-substituted 3-chlorophenylpiperazine motif in nefazodone, six were derived from mono- and bis-hydroxylation, and one was derived from the Baeyer Villiger oxidation of the ethyltriazolone moiety in nefazodone.

Sihler's stain is a whole mount nerve staining technique that renders other soft tissue translucent or transparent while staining the nerves. It permits mapping of entire nerve supply patterns of organs, skeletal muscles, mucosa, skin, and other structures after the specimens are fixed in neutralized formalin, macerated in potassium hydroxide, decalcified in acetic acid, stained in Ehrlich's hematoxylin, destained in acetic acid, and cleared in glycerin. The unique advantage of Sihler's stain over other anatomical methods is that all the nerves within the stained specimen can be visualized in their three-dimensional positions. To date, Sihler's stain is the best tool for demonstrating the precise intramuscular branching and distribution patterns of skeletal muscles, which are important not only for anatomists, but also for physiologists and clinicians. Advanced knowledge of the neural structures within mammalian skeletal muscles is critical for understanding muscle functions, performing electrophysiological experiments and developing novel neurosurgical techniques. In this review, Sihler's stain is described in detail and its use in nerve mapping is surveyed. Special emphasis is placed on staining procedures and troubleshooting, strengths and limitations, applications, major contributions to neuroscience, physiological and clinical significance, and areas for further technical improvement that deserve future research.

Strains of Sweet potato feathery mottle virus (SPFMV; Potyvirus; Potyviridae) infecting sweet-potato (Ipomoea batatas) in Oceania, one of the worlds' earliest sweetpotato-growing areas, and in southern Africa were isolated and characterized phylogenetically by analysis of the coat protein (CP) encoding sequences. Sweetpotato plants from Easter Island were co-infected with SPFMV strains C and EA. The EA strain isolates from this isolated location were related phylogenetically to those from Peru and East Africa. Sweetpotato plants from French Polynesia (Tahiti, Tubuai, and Moorea) were co-infected with SPFMV strains C, O, and RC in different combinations, whereas strains C and RC were detected in New Zealand. Sweetpotato plants from Zimbabwe were infected with strains C and EA and those from Cape Town, South Africa, with strains C, O, and RC. Co-infections with SPFMV strains and Sweet potato virus G (Potyvirus) were common and, additionally, Sweet potato chlorotic fleck virus (Carlavirus) was detected in a sample from Tahiti. Taken together, occurrence of different SPFMV strains was established for the first time in Easter Island, French Polynesia, and New Zealand, and new strains were detected in Zimbabwe and the southernmost part of South Africa. These results from the Southern hemisphere reflect the anticipated global distribution of strains C, O, and RC but reveal a wider distribution of strain EA than was known previously.

Transforming growth factor-beta (TGF-beta)-mediated signals play complicated roles in the development and progression of breast tumour. The purposes of this study were to analyse the genotype of TGF-beta1 at T29C and TGF-beta1 phenotype in breast tumours, and to evaluate their associations with IGFs and clinical characteristics of breast cancer. Fresh tumour samples were collected from 348 breast cancer patients. TGF-beta1 genotype and phenotype were analysed with TaqMan and ELISA, respectively. Members of the IGF family in tumour tissue were measured with ELISA. Cox proportional hazards regression analysis was performed to assess the association of TGF-beta1 and disease outcomes. Patients with the T/T (29%) genotype at T29C had the highest TGF-beta1, 707.9 pg mg(-1), followed by the T/C (49%), 657.8 pg mg(-1), and C/C (22%) genotypes, 640.8 pg mg(-1), (P=0.210, T/T vs C/C and C/T). TGF-beta1 concentrations were positively correlated with levels of oestrogen receptor, IGF-I, IGF-II and IGFBP-3. Survival analysis showed TGF-beta1 associated with disease progression, but the association differed by disease stage. For early-stage disease, patients with the T/T genotype or high TGF-beta1 had shorter overall survival compared to those without T/T or with low TGF-beta1; the hazard ratios (HR) were 3.54 (95% CI: 1.21-10.40) for genotype and 2.54 (95% CI: 1.10-5.89) for phenotype after adjusting for age, grade, histotype and receptor status. For late-stage disease, however, the association was different. The T/T genotype was associated with lower risk of disease recurrence (HR=0.13, 95% CI: 0.02-1.00), whereas no association was found between TGF-beta1 phenotype and survival outcomes. The study suggests a complex role of TGF-beta1 in breast cancer progression, which supports the finding of in vitro studies that TGF-beta1 has conflicting effects on tumour growth and metastasis.

Sweet potato virus G (SPVG, genus Potyvirus, family Potyviridae) was detected in sweetpotato (Ipomoea batatas) storage roots sold in the local markets and storage roots or cuttings sampled directly from farmers' fields. Using serological and molecular methods, the virus was detected for the first time in Java, New Zealand, Hawaii, Tahiti, Tubuai, Easter Island, Zimbabwe, and South Africa, and also in an imported storage root under post-entry quarantine conditions in Western Australia. In some specimens, SPVG was detected in mixed infection with Sweet potato feathery mottle virus (genus Potyvirus). The coat protein (CP) encoding sequences of SPVG were analyzed for 11 plants from each of the aforementioned locations and compared with the CP sequences of 12 previously characterized isolates from China, Egypt, Ethiopia, Spain, Peru, and the continental United States. The nucleotide sequence identities of all SPVG isolates ranged from 79 to 100%, and amino acid identities ranged from 89 to 100%. Isolates of the same strain of SPVG had nucleotide and amino acid sequence identities from 97 to 100% and 96 to 100%, respectively, and were found in sweetpotatoes from all countries sampled except Peru. Furthermore, a plant from Zimbabwe was co-infected with two clearly different SPVG isolates of this strain. In contrast, three previously characterized isolates from China and Peru were phylogenetically distinct and exhibited <90% nucleotide identity with any other isolate. So far, the highest genetic diversity of SPVG seems to occur among isolates in China. Distribution of SPVG within many sweetpotato growing areas of the world emphasizes the need to determine the economic importance of SPVG.

Reason for Performing Study: Studies are required to define more accurately and completely the neuroanatomy of the equine dorsal cricoarytenoid muscle as a prerequisite for developing a neuroprosthesis for recurrent laryngeal neuropathy., Objectives: To describe the anatomy, innervation, fibre types and function of the equine dorsal cricoarytenoid muscle., Methods: Thirty-one larynges were collected at necropsy from horses with no history of upper airway disease and 25 subjected to gross dissection. Thereafter, the following preparations were made on a subset of larynges: histochemical staining (n = 5), Sihler's and acetylcholinesterase staining for motor endplates (n = 2). An additional 6 larynges were collected and used for a muscle stimulation study., Results: Two neuromuscular compartments (NMC), each innervated by a primary nerve branch of the recurrent laryngeal nerve, were identified in all larynges. Stimulation of the lateral NMC produced more lateral displacement of the arytenoid cartilage than the medial NMC (P<0.05). The medial NMC tended to rotate the arytenoid cartilage dorsally. Motor endplates were identified at the junction of the middle and caudal thirds of each NMC. If fibre type grouping was present it was always present in both NMCs., Conclusions: The equine dorsal cricoarytenoid muscle has 2 distinct muscle NMCs with discrete innervation and lines of action. The lateral NMC appears to have a larger role in increasing cross-sectional area of the rima glottidis., Potential Relevance: This information should assist in planning surgical reinnervation procedures and development of a neuroprosthesis for recurrent laryngeal neuropathy.

We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-gamma ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination.

d-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) has great potential in pharmacology and nanotechnology. The present work investigated the molecular behaviour of TPGS at the air-water interface, its effect on a model bio-membrane composed of dipalmitoylphosphatidylcholine (DPPC) lipid monolayer, and the interaction between the TPGS coated nanoparticles with the lipid model membrane. Paclitaxel loaded polymeric nanoparticles with TPGS as surfactant stabiliser were fabricated and characterised in terms of their drug incorporation capability and release kinetics. The result showed that TPGS exhibited notable effect on the surface properties of air-water interface as well as the lipid monolayer. The inter-particle force and the interaction between nanoparticles and lipid monolayer varied with the surface substance. The penetration of various nanoparticles into the model membrane indicated that an optimal balance between hydrophilicity and hydrophobicity on nanoparticle surface is needed to achieve an effective cellular uptake of nanoparticles. The results also demonstrate that the drug incorporation capability and the release characteristics of drug-loaded nanoparticles can be influenced by surfactant stabiliser.

Micelles from the mixture of poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) and d-alpha-tocopheryl polyetheyene glycol 1000 succinate (TPGS) were prepared loaded with the poorly soluble anticancer drug camptothecin (CPT). The solubilization of CPT by the mixed micelles was more efficient than with earlier described micelles made of PEG-PE alone. CPT-loaded mixed micelles were stable upon storage and dilution and firmly retained the incorporated drug. The cytotoxicity of the CPT-loaded mixed micelles against various cancer cells in vitro was remarkably higher than that of the free drug. PEG-PE/TPGS mixed micelles may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

Paclitaxel (Taxol) is one of the best antineoplastic drugs found from nature in the past decades. Like many other anticancer drugs, there are difficulties in its clinical administration due to its poor solubility. Therefore an adjuvant called Cremophor EL has to be employed, but this has been found to cause serious side-effects. However, nanoparticles of biodegradable polymers can provide an ideal solution to the adjuvant problem and realise a controlled and targeted delivery of the drug with better efficacy and fewer side-effects. The present research proposes a novel formulation for fabrication of nanoparticles of biodegradable polymers containing d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) to replace the current method of clinical administration and, with further modification, to provide an innovative solution for oral chemotherapy. In the modified solvent extraction/evaporation technique employed in this research, the emulsifier/stabiliser/additive and the matrix material can play a key role in determining the morphological, physicochemical and pharmaceutical properties of the produced nanoparticles. We found that vitamin E TPGS could be a novel surfactant as well as a matrix material when blended with other biodegradable polymers. The nanoparticles composed of various formulations and manufactured under various conditions were characterised by laser light scattering (LLS) for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray photoelectron spectroscopy (XPS) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. The drug encapsulation efficiency (EE) and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography (HPLC). It was concluded that vitamin E TPGS has great advantages for the manufacture of polymeric nanoparticles for controlled release of paclitaxel and other anti-cancer drugs. Nanoparticles of nanometer size with narrow distribution can be obtained. A drug encapsulation efficiency as high as 100% can be achieved and the release kinetics can be controlled.

The D-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was applied in the present investigation as surfactant stabiliser to fabricate paclitaxel-loaded PLGA nanospheres in the solvent evaporation/extraction technique with successful achievement. Laser light scattering system (LLS), scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were employed to characterise the nanopsheres fabricated in various recipes under various preparation conditions for size and size distribution, surface morphology, thermogram property and surface chemistry. Encapsulation efficiency and in vitro release was measured by the high-performance liquid chromatography (HPLC). The outcomes were discussed with respect to the development of polymeric nanospheres delivery system of the anticancer drug, paclitaxel (Taxol((R))). The produced nanospheres were found in fine spherical shape with smooth surfaces and without aggregation or adhesion. There was no significant difference in morphology between the vitamin E TPGS emulsified and PVA emulsified PLGA nanospheres. However, it was found that, in comparison with the traditional chemical emulsifier PVA, the TPGS could significantly improve the encapsulation efficiency of the drug in the PLGA nanospheres, which could be as high as 100%. The size of the vitamin E TPGS emulsified nanospheres ranged from 300 to 800 nm and the size distribution was narrow with polydispersity of 0.005-0.045. XPS investigation demonstrated that there were residual surfactant molecules remained on the surface although the TPGS could be washed out relatively thoroughly in the process of nanospheres formation. This finding was also confirmed by FTIR-PAS investigation of the nanospheres. The in vitro release indicated that the release property of paclitaxel from the nanospheres strongly depends on the emulsifier type employed in the fabrication. Our research shows that vitamin E TPGS could be an ideal and effective emulsifier.