One-Pot Facile Encapsulation of Dimethyloxallyl Glycine by Nanoscale Zeolitic Imidazolate Frameworks-8 for Enhancing Vascularized Bone Regeneration.

In the process of bone tissue regeneration, regulation of osteogenesis-angiogenesis coupling is of great importance. Therefore, dimethyloxallyl glycine (DMOG) is loaded by nanoscale zeolitic imidazolate frameworks-8 (ZIF-8) to obtain a drug-loading system that can promote osteogenesis-angiogenesis coupling. Characterization of the drug-loading nanoparticles (DMOG@ZIF-8) reveals that DMOG is successfully loaded into ZIF-8 by two different methods, and the DMOG@ZIF-8 is prepared using the one-pot method (OD@ZIF-8) achieves higher loading efficiency and longer release time than those prepared using the post-loading method (PD@ZIF-8). In vitro studies found that DMOG@ZIF-8 significantly enhances the migration, tube formation, and angiogenesis-related protein secretion of human umbilical vein endothelial cells as well as the extracellular matrix mineralization, alkaline phosphatase activity, and osteogenesis-related protein secretion of bone marrow mesenchymal stem cells. Moreover, OD@ZIF-8 nanoparticles are more efficient than PD@ZIF-8 nanoparticles in induction of osteogenesis-angiogenesis coupling. Then, in vivo cranial critical defect model shows that the addition of OD@ZIF-8 significantly promotes vascularized bone formation as indicated by the results including microcomputed tomographic, histological and immunofluorescence staining, and so on. Taken together, loading ZIF-8 with DMOG may be a promising solution for critical-sized bone defect reconstruction and the one-pot method is preferred in the preparation of such drug-loading system.

Comparison of survival, acute toxicities, and dose-volume parameters between intensity-modulated radiotherapy with or without internal target volume delineation method and three-dimensional conformal radiotherapy in cervical cancer patients: A retrospective and propensity score-matched analysis.

BACKGROUND: To evaluate whether the use of the internal target volume (ITV) delineation method improves the performance of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in terms of survival, acute toxicities, and dose-volume parameters. METHODS: A total number of 477 cervical cancer patients who received concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016 were retrospectively analyzed. They were divided into four groups: the non-ITV (N-ITV) + IMRT, ITV + IMRT, N-ITV + 3DCRT, and ITV + 3DCRT groups, with 76, 41, 327, and 33 patients, respectively. Survival analysis was performed with the Kaplan-Meier and the log-rank tests, and acute toxicity analysis was performed with the chi-squared test and the binary logistic regression test. Using the propensity score matching (PSM) method, 92 patients were matched among the four groups, and their dose-volume parameters were assessed with the Kruskal-Wallis method. RESULTS: The median follow-up time was 49 months (1-119) for overall survival (OS). The 5-year OS rate was 66.4%. The ITV delineation method was an independent prognostic factor for OS (HR [95% CI]: 0.52 [0.27, 0.98], p = 0.044) and progression-free survival (PFS) (HR [95% CI]: 0.59 [0.36, 0.99], p = 0.045). The ITV + IMRT group had the lowest incidence rate (22%) and the N-ITV + IMRT group had the highest incidence rate of grade ≥3 hematological toxicity (HT) (46.1%) among the four groups. The pelvic bone marrow relative V10, V20, and V30 in the N-ITV + IMRT group was higher than those in the ITV + IMRT and N-ITV + 3DCRT groups (p < 0.05). CONCLUSIONS: The use of ITV for IMRT treatment planning was associated with improved overall survival and progression-free survival, with lower HT rate.

Eyelid margin cleaning using Deep Cleaning Device for the treatment of meibomian gland dysfunction-associated dry eye: a preliminary investigation.

OBJECTIVE: To evaluate the safety and effectiveness of eyelid margin cleaning using Deep Cleaning Device for the treatment of meibomian gland dysfunction-associated dry eye. METHODS: This was a prospective, randomized, open-label, investigator-masked, and self-controlled study. We randomly assigned one eye of patients with meibomian gland dysfunction-associated dry eye to the treatment group, and the other eye to the control group. Both groups received artificial tears and lid warming; the treatment group received an additional one-time in-office eyelid margin cleaning using Deep Cleaning Device. Non-invasive tear break-up time (NITBUT) and tear meniscus height (TMH) of each eye, and Standard Patient Evaluation for Eye Dryness II (SPEED II) score of each patient were evaluated before and at one week after treatment. RESULTS: Thirty eyes of 15 patients were enrolled. No adverse effects occurred during the treatment. Compared with the baseline values, the SPEED score decreased significantly at one week after treatment (mean±95% confidence interval, 11.00±0.99 vs. 5.67±1.67, P<0.0001), the NITBUT-first in the treatment group increased significantly at one week after treatment ((4.74±1.27) s vs. (7.49±2.22) s, P=0.01). The NITBUT-first was significantly longer in the treatment group ((7.49±2.22) s) than in the control group ((5.17±0.91) s) at one week after treatment (P=0.042). No significant differences were found in other tear film parameters between the two groups. CONCLUSIONS: Eyelid margin cleaning using the novel Deep Cleaning Device is a convenient, effective, and safe treatment for patients with meibomian gland dysfunction-associated dry eye.

Effects of corneal thickness distribution and apex position on postoperative refractive status after full-bed deep anterior lamellar keratoplasty.

OBJECTIVE: To investigate the effects of corneal thickness distribution and apex position on postoperative refractive status after full-bed deep anterior lamellar keratoplasty (FBDALK). METHODS: This is a retrospective analysis of patients who were diagnosed with advanced keratoconus between 2011 and 2014 in our hospital. The base of the cone in all patients did not exceed the central cornea at a 6-mm range. The FBDALK was performed by a same surgeon. All patients had a complete corneal suture removal and the follow-up records were intact. Patients who had graft-bed misalignment or who were complicated with a cataract or glaucoma were excluded. Uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), and Pentacam examination data were recorded at two years postoperatively. The recorded data included the superior-inferior (S-I) and nasal-temporal (N-T) corneal thickness differences in 2, 4, 6, and 8 mm diameter concentric circles with the corneal apex as the center (S-I2 mm, S-I4 mm, S-I6 mm, S-I8 mm, N-T2 mm, N-T4 mm, N-T6 mm, and N-T8 mm), the linear, X-axis, and Y-axis distance between the corneal pupillary center and the cornea apex, total corneal astigmatism at a zone of 3 mm diameter from the corneal apex (TA3 mm), the astigmatic vector values J0 and J45, and the corneal total higher-order aberration for 3 and 6 mm pupil diameters (HOA3 mm and HOA6 mm). Statistical analysis was performed by SPSS 15.0. RESULTS: A total of 47 eyes of 46 patients met the criteria and were included in this study. The mean follow-up time was (28±7) months. The mean UCVA was 0.45±0.23 (logMAR) (MAR: minimum angle of resolution) and the mean BSCVA was 0.19±0.15 (logMAR), which were all significantly positively correlated with postoperative TA3 mm and HOA3 mm. The mean S-I corneal thickness differences were (44.62±37.74) µm, and the mean N-T was (38.57±32.29) µm. S-I2 mm was significantly positively correlated with J0 (r=0.31), J45 (r=0.42), HOA3 mm (r=0.37), and HOA6 mm (r=0.48). S-I4 mm and S-I8 mm were significantly positively correlated with HOA3 mm (r=0.30, r=0.40) and HOA6 mm (r=0.46, r=0.35). The X-axis distance between corneal pupillary center and corneal apex was significantly positively correlated with J45 (r=0.29). CONCLUSIONS: In patients with advanced keratoconus after FBDALK, the unevenly distributed thickness at corneal pupillary area and the misalignment of corneal apex and pupillary center might cause significant regular and irregular astigmatism, which affected the postoperative visual quality.

Assessments of tear meniscus height, tear film thickness, and corneal epithelial thickness after deep anterior lamellar keratoplasty.

OBJECTIVE: To assess the lower tear meniscus height (LTMH), central tear film thickness (CTFT), and central corneal epithelial thickness (CCET) after deep anterior lamellar keratoplasty (DALK). METHODS: This was a retrospective cross-sectional study of 20 patients who had DALK in one eye over a three-month period. LTMH, CTFT, and CCET of the operated eyes and the unoperated fellow eyes were measured using high-definition optical coherence tomography (HD-OCT). Correlations between three OCT assessments and age, time following surgery, graft size, bed size, and the number of residual sutures were analyzed. RESULTS: Compared to patients with keratoconus, patients with other corneal conditions had significantly higher CCET in the fellow eye (P=0.024). For all patients, CCET in the operated eye was significantly negatively correlated with the number of residual sutures (R=-0.579, P=0.008), and was significantly positively correlated with time following surgery (R=0.636, P=0.003). In the fellow eye, a significant positive correlation was found between age and CCET (R=0.551, P=0.012), and a significant negative correlation between age and CTFT (R=-0.491, P=0.028). LTMH was found to be significantly correlated between operated and fellow eyes (R=0.554, P=0.011). There was no significant correlation between LTMH and age, bed/graft size, time following surgery, or residual sutures (all possible correlations, P>0.05). CONCLUSIONS: Patients with keratoconus tend to have a thinner central corneal epithelium. Corneal epithelium keeps regenerating over time after DALK. DALK did not induce a significant change in tear volume compared with the fellow eye. Postoperative tear function might depend on an individual's general condition, rather than on age, gender, bed/graft size, time following surgery, or residual sutures.

Satisfactory clinical outcome following delayed repositioning of a traumatic post-LASIK flap with dislocation and shrinkage managed by irrigation, stretching, and debridement.

OBJECTIVE: To report surgical management and favorable outcome in a case with delayed repair of traumatic laser in situ keratomileusis (LASIK) flap dislocation with shrinkage and folds. METHODS: A 30-year-old man with a five-year history of bilateral LASIK experienced blunt trauma to his right eye followed by decreased vision for 5 weeks. The surgical management included initially softening the flap by irrigation with balanced salt solution (BSS). The shrinkage folds were carefully and gently stretched by scraping with a 26-gauge cannula accompanied by BSS irrigation. All of the epithelial ingrowth on the flap inner surface and on the bed was thoroughly debrided by scraping and irrigation. After the flap was repositioned to match its original margin, a soft bandage contact lens was placed. RESULTS: At his initial visit, slit-lamp microscopy and optical coherence tomography (OCT) showed shrinkage of the LASIK flap with an elevated margin approximately 3 mm above the original position. The flap covered half of the pupil and had multiple horizontal folds. Two months after surgery, the flap remained well positioned with only faint streaks in the anterior stroma. The uncorrected visual acuity of the right eye was 20/20 with a manifest refraction of Plano. CONCLUSIONS: For delayed repair of traumatically dislocated LASIK flaps, sufficient softening by BSS, stretching the shrinkage folds, and thorough debridement of ingrowth epithelium enable resetting the flap and provide satisfactory results.

Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.

OBJECTIVE: To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). METHODS: We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. RESULTS: Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. CONCLUSION: ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. ADVANCES IN KNOWLEDGE: Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

Dosimetric Evaluation of a Simple Planning Technique for Improving Intensity-Modulated Radiotherapy for Nasopharyngeal Cancer.

PURPOSE: To evaluate the dosimetric outcomes of a simple planning technique for improving intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer (NPC). METHODS: For 39 NPC cases, generally acceptable original plans were generated and were improved by the two planning techniques, respectively: (1) a basal-dose-compensation (BDC) technique, in which the treatment plans were re-optimized based on the original plans; (2) a local-dose-control (LDC) technique, in which the original plans were re-optimized with constraints for hot and cold spots. The BDC, original, and LDC plans were then compared regarding homogeneity index (HI) and conformity index (CI) of planning target volumes (PTVs), organ-at-risk (OAR) sparing and monitor units (MUs) per fraction. The whole planning times were also compared between the BDC and LDC plans. RESULTS: The BDC plans had superior HIs / CIs, by 13-24% / 3-243%, respectively, over the original plans. Compared to the LDC plans, the BDC plans provided better HIs only for PTVnx (the PTV of nasopharyngeal primary tumor) by 11% and better CIs for all PTVs by 2-134%. The BDC technique spared most OARs, by 1-9%. The average MUs of the BDC, original, and LDC plans were 2149, 2068 and 2179, respectively. The average whole planning times were 48 and 69 minutes for the BDC and LDC plans, respectively. CONCLUSIONS: For the IMRT of nasopharyngeal cancer, the BDC planning technique can improve target dose homogeneity, conformity and OAR sparing, with better planning efficiency.

Improving target coverage and organ-at-risk sparing in intensity-modulated radiotherapy for cervical oesophageal cancer using a simple optimisation method.

PURPOSE: To assess the performance of a simple optimisation method for improving target coverage and organ-at-risk (OAR) sparing in intensity-modulated radiotherapy (IMRT) for cervical oesophageal cancer. METHODS: For 20 selected patients, clinically acceptable original IMRT plans (Original plans) were created, and two optimisation methods were adopted to improve the plans: 1) a base dose function (BDF)-based method, in which the treatment plans were re-optimised based on the original plans, and 2) a dose-controlling structure (DCS)-based method, in which the original plans were re-optimised by assigning additional constraints for hot and cold spots. The Original, BDF-based and DCS-based plans were compared with regard to target dose homogeneity, conformity, OAR sparing, planning time and monitor units (MUs). Dosimetric verifications were performed and delivery times were recorded for the BDF-based and DCS-based plans. RESULTS: The BDF-based plans provided significantly superior dose homogeneity and conformity compared with both the DCS-based and Original plans. The BDF-based method further reduced the doses delivered to the OARs by approximately 1-3%. The re-optimisation time was reduced by approximately 28%, but the MUs and delivery time were slightly increased. All verification tests were passed and no significant differences were found. CONCLUSION: The BDF-based method for the optimisation of IMRT for cervical oesophageal cancer can achieve significantly better dose distributions with better planning efficiency at the expense of slightly more MUs.

More accurate definition of clinical target volume based on the measurement of microscopic extensions of the primary tumor toward the uterus body in international federation of gynecology and obstetrics Ib-IIa squamous cell carcinoma of the cervix.

PURPOSE: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). PATIENTS AND METHODS: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. RESULTS: Microscopic extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. CONCLUSION: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.

Dielectrophoretic placement of quasi-zero-, one-, and two-dimensional nanomaterials into nanogap for electrical characterizations.

DEP is one of promising techniques for positioning nanomaterials into the desirable location for nanoelectronic applications. In contrast, the lithography technique is commonly used to make ultra-thin conducting wires and narrow gaps but, due to the limit of patterning resolution, it is not feasible to make electrical contacts on ultra-small nanomaterials for a bottom-up device fabrication. Thus, integrating the lithography and dielectrophoresis, a real bottom-up fabrication can be achieved. In this work, the device with the nanogap in between two nanofinger-electrodes is made using electron-beam lithography from top down and the ultra-small nanomaterials, such as colloidal PbSe quantum dots, polyaniline nanofibers, and reduced-graphene-oxide flakes, are placed in the nanogap by DEP from bottom up. The threshold electric field for the DEP placement of PbSe nanocrystals was roughly estimated to be about 8.3 × 10(4) V/cm under our experimental configuration. After the DEP process, several procedures for reducing contact resistances are attempted and measurements of intrinsic electron transport in versatile nanomaterials are performed. It is experimentally confirmed that electron transport in both PbSe nanocrystal arrays and polyaniline nanofibers agrees well with Prof. Ping Sheng's model of granular metallic conduction. In addition, electron transport in reduced-graphene-oxide flakes follows Mott's 2D variable-range-hopping model. This study illustrates an integration of the electron-beam lithography and the DEP techniques for a precise manipulation of nanomaterials into electronic circuits for characterization of intrinsic properties.

Nano approach investigation of the conduction mechanism in polyaniline nanofibers.

A nanotechnological approach is applied to measurements of the electric field dependence of resistance under a high electric field while in low voltage. With this technique, the conduction mechanism on a mesoscopic scale is explored in a single, nonagglomerated nanofiber. Polyaniline nanofibers are prepared by vigorous mixing of aniline and oxidation agent ammonium persulfate in acid solution. They exhibit a uniform nanoscale morphology rather than agglomeration as that produced via conventional chemical oxidation. The as-synthesized polyaniline nanofibers are doped (dedoped) with a HCl acid (NH(3) base), and their temperature behaviors of resistances follow an exponential function with an exponent of T(-1/2). To measure the conduction mechanism in a single nanofiber, the dielectrophoresis technique is implemented to position nanofibers on top of two electrodes with a nanogap of 100-600 nm, patterned by electron-beam lithography. After the devices are irradiated by electron beam to reduce contact resistances, their temperature behaviors and electric field dependences are unveiled. The experimental results agree well with the theoretical model of charging energy limited tunneling. Other theoretical models such as Efros-Shklovskii and Mott's one-dimensional hopping conduction are excluded after comparisons and arguments. Through fitting, the size of the conductive grain, separation distance between two grains, and charging energy per grain in a single polyaniline nanofiber are estimated to be about 4.9 nm, 2.8 nm, and 78 meV, respectively. The nanotechnological approach, where the nanogap and the dielectrophoresis technique are used for single nanofiber device fabrication, is applied for determination of mesoscopic charge transport in a polyaniline conducting polymer.

[Application study of the 2008 staging system of nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: The 2008 staging system of nasopharyngeal carcinoma (NPC) was generated based on the NPC 92 and AJCC staging system. It remains open to be consummated. This study was to evaluate its rationality as well as compare the stage distribution among the 3 staging systems, by using of MRI imaging. METHODS: MRI data was collected from a cohort of 177 cases of untreated NPC for retrospective review. We accepted the nasal involvement criteria of 2008 staging system, in which the borderline between the nasal cavity and nasopharynx was a line linked between both posterior walls of the maxillary sinus, for all of the 3 systems. RESULTS: Involvement of oropharynx, nasopharynx, soft palatine, prevertebral muscles, post-styloid space, intracranial, orbit, 1st and/or 2nd cervical body are 100% accompanied with other same or more advanced T-stage classifications. The same situations happened in more than 95% of involvement of the medial pterygoid muscle or masticator space beyond it. Cervical lymph node metastasis (LNM) accounted for 76.3%. Proportion of metastatic lymph node extracapsular extension (ECE) and/or bilateral neck LNM elevated as maximum diameter of the node increased, no matter transverse or longitudinal. There were 11 cases of parotid LNM in this group. Advanced stage accounted for 81.4%, 78.5% and 75.7% in 2008, UICC and NPC 92 staging system, respectively, without statistic difference. CONCLUSION: Nasal involvement criteria and T-stage classification of the medial pterygoid muscle defined by NPC 2008 staging system seems reasonable. Stage distribution is also similar to the other 2 systems. However, diameter of the LNM might not be a prognostic factor. Parameters such as how to classify a parotid LNM, or a node which occupies more than one region, require further clarify.

Nanoscale surface electrical properties of zinc oxide films investigated by conducting atomic force microscopy.

In this study, conducting atomic force microscopy was employed to investigate the nanoscale surface electrical properties of zinc oxide (ZnO) films prepared by pulsed laser deposition (PLD) at different substrate temperatures for use as anode materials in polymer light-emitting diodes. The results show that the surface conductivity distribution of ZnO is related to its surface structure. At substrate temperatures of 150-200 degrees C, the conducting regions may cover over 90% of the ZnO thin-film surface, thus providing the best local conductivity. Moreover, heating at substrate temperatures of above 250 degrees C can effectively make the conductivity on the ZnO surface uniform. In particular, at substrate temperatures of around 300 degrees C, the conducting regions where currents are between 1 and 2 muA may cover as much as 83% of the surface, and furthermore, the transmission ratio in the visible range is higher than 80%. This is a rather ideal production temperature for the PLD for ZnO films.