Comparison of photodynamic therapy with two different parameters combined with subconjunctival injection of bevacizumab for corneal neovascularization.

BACKGROUND: To the best of our knowledge, no studies have been performed to determine the optimal parameters of photodynamic therapy (PDT) combined with subconjunctival injection of bevacizumab for corneal neovascularization. This study aimed to compare the effect of photodynamic therapy with two different sets of parameters combined with subconjunctival injection of bevacizumab for corneal neovascularization. METHODS: Patients with stable corneal neovascularization (CNV) unresponsive to conventional treatment (topical steroid) were included in this study. Patients were divided into two groups, receiving PDT with two different sets of parameters (group 1 receiving fluence of 50 J/cm2 at 15 min after intravenous injection of verteporfin with, group 2 receiving fluence of 150 J/cm2 at 60 min after intravenous injection of verteporfin with). Subconjunctival injection of bevacizumab was performed immediately after PDT. All patients were followed for 6 months. Best-corrected visual acuity and intraocular pressure were evaluated, and slit-lamp biomicroscopy as well as digital photography were performed. Average diameter and cumulative length of corneal neovascular were measured to evaluate the corneal neovascularization. RESULTS: Seventeen patients (20 eyes) were included in this study. At the last visit, the vision was improved in 12 eyes (60 %), steady in 4 eyes (20 %) and worsen in 4 eyes (20 %). The intraocular pressure (IOP) of all patients remained in normal range. A significant decrease in corneal neovascularization was showed in all the eyes after treatment. At 6 months after the combined treatment, the average diameter and cumulative length of vessels significantly decreased to 0.041 ± 0.023 mm (P < 0.05) and 18.78 ± 17.73 mm (P < 0.05), respectively, compared with the pretreatment data (0.062 ± 0.015 mm, 31.48 ± 18.21 mm). The reduction was more remarkable in group 2 compared to group 1.In group 1, the average diameter was 0.062 ± 0.013mm before and 0.056 ± 0.017mm after, the cumulative length of vessels was 38.66 ± 22.55mm before and 31.21 ± 17.30 after. In group 2, the date were 0.061 ± 0.016mm before and 0.029 ± 0.020mm after, 25.60 ± 8.95 mm before and 8.61 ± 8.26 mm. The reported complications included epithelial defect in four eyes, small white filaments in two eyes and corneal epithelial erosion in two eyes. CONCLUSION: The PDT combined with subconjunctival injection of bevacizumab was effective for the chronic corneal neovascularization. A more promising treatment outcome was observed when PDT was performed at 60 min after intravenous injection of verteporfin with fluence of 150 J/cm2. No serious complications or systemic events were observed throughout the follow-up period.

Characteristics of the Peripapillary Structure and Vasculature in Patients With Myopic Anisometropia.

Purpose: To evaluate the interocular differences of the peripapillary structural and vascular parameters and that of association with axial length (AL) in participants with myopic anisometropia using swept-source optical coherence tomography. Methods: This prospective cross-sectional study included 90 eyes of 45 participants. Each participant's eyes were divided into the more and less myopic eye respectively according to spherical equivalent. The ß- and γ-parapapillary atrophy (PPA) areas, Bruch's membrane opening distance, border length, and border tissue angle were measured manually. Peripapillary choroidal vascularity index and choroidal thickness (CT) values in superior, nasal, inferior, and temporal were calculated using a custom-built algorithm based on MATLAB. Results: The interocular difference in AL and spherical equivalent was 0.62 ± 0.26 mm and -1.50 (-2.13, -1.25) diopters (D), respectively. The interocular difference in spherical equivalent was highly correlated with that of the AL. The ß- and γ-PPA areas were significantly greater in more myopic eyes. The mean and inferior peripapillary choroidal vascularity index and all regions of peripapillary CT were significantly lower in the more myopic eyes. The interocular difference in AL was significantly positively correlated with the interocular differences in γ-PPA area and border length and negatively correlated with the interocular differences in temporal choroidal vascularity index and mean, inferior, and temporal peripapillary CT. There was an independent correlation between the interocular differences in AL and the interocular differences in γ-PPA area, inferior, and temporal peripapillary CT. Conclusions: Significant differences between both groups were detected in most peripapillary parameters, especially in peripapillary CT. The γ-PPA area, border length, and peripapillary CT were significantly correlated with the elongation of AL. Translational Relevance: The current study characterized and analyzed the peripapillary parameters in myopic anisometropia, which helped to monitor myopic progression.

A vault-prediction formula for implantable collamer lens based on preoperative parameters: a retrospective clinical study.

OBJECTIVES: The aim of the present study was to predict the vault of implantable collamer lens (ICL) using a formula established based on the preoperative parameters. METHODS: This retrospective study included data on 226 eyes from 114 patients(the median age and range was 27.5 ± 5.7; 18-46 years) who underwent EVO-ICL surgery between May 2021 and April 2022. Preoperative parameters, such as anterior chamber depth (ACD) horizontal angle-to-angle diameter (ATA), Crystalline lens rise (CLR), and vault (1 week after surgery) were measured by anterior segment optical coherence tomography. The axial length of eyes (AL) and white-to-white (WTW) values were measured using an IOLmaster and calipers under a slit lamp separately. RESULT: The mean WTW, ACD, horizontal ATA diameter, CLR, AL, and vault 1 week after surgery were 11.42 ± 0.37 mm, 3.25 ± 0.25 mm, 11.72 ± 0.44 mm, 45.78 ± 175.42 µm, 27.61 ± 1.93 mm, and 586.51 ± 254.54 µm respectively. Multivariate regression analysis showed that the ICL-width, ACD (ß = 0.293), ATA (ß =-0.657), CLR (ß =-0.157), and the anterior chamber angle in temporal side (T:ACA) (ß=-0.277) were predictors of the vault size (adjusted-R2 = 0.39, P < 0.001). CONCLUSION: The formula built based on these preoperative parameters could be used to predict the vault before surgery. The predictors indicated that the pre-operative parameters of eye such as ACD, ATA, CLR and T:ACA play an important role in choosing optimal ICL size.

Development and validation of a new multivariable prediction model to estimate risk of abnormal vault.

PURPOSE: To develop and validate a new multivariable prediction model to estimate risk of abnormal vault after EVO Implantable Collamer Lens (EVO-ICL) implantation using the preoperative parameters. METHODS: This retrospective study comprised 282 eyes of 143patients who underwent EVO-ICL surgery between May 2021 and April 2022. We measured preoperative parameters before surgery and vaults in 1 week after the operation using swept-source optical coherence tomography (SS-OCT). Risk factors for abnormal vault were determined by univariate and multivariate logistic regression analyses, and a nomogram was developed to forecast the risk of abnormal vault after EVO-ICL implantation. We assessed the performance of nomogram in terms of discrimination and calibration, including concordance index (C-index), receiver operating characteristic curve (ROC), area under the ROC curve (AUC), and decision curve analysis (DCA). Bootstrap resampling was used as an internal verification method. RESULTS: The logistic regression analysis revealed the independent risk factors for abnormal vault were white-to-white(WTW), anterior chamber angle(ACA), pupil size, and ICL-size, all of them were used to establish a nomogram based on multivariate logistic regression to predict the risk of abnormal vault. The C-indexes and AUC were 0.669 (95%CI, 0.605, 0.733). The calibration curves of the nomogram showed relatively small bias from the reference line, implicating an acceptable degree of confidence. The DCA indicates the potential clinical significance of the nomogram. CONCLUSIONS: We developed a new multivariable prediction model to estimate risk of abnormal vault. The model shows good prediction effect and can provide assistance for clinical decision of ICL size.

Short-term postoperative changes in the choroidal vascularity index in patients with a unilateral epiretinal membrane.

BACKGROUND: To investigate short-term choroidal structural and vascular changes after epiretinal membrane (ERM) surgery. METHODS: In this retrospective study, 65 patients with unilateral ERM underwent pars plana vitrectomy combined with cataract surgery and were examined one day before surgery and one week, one month, and three months after surgery. Choroidal thickness (CT) and choroidal vascular index (CVI) were evaluated using horizontal enhanced depth imaging optical coherence tomography (EDI-OCT) scans and were further calculated using semi-automatic algorithms using MATLAB R2017a. RESULTS: Preoperatively, CVI was higher in eyes with ERM (61.70 ± 5.17%) than in fellow eyes (59.99 ± 5.26%). CVI increased significantly at one week after surgery (62.14 ± 5.02%) and decreased at 1 and 3 months after surgery (60.76 ± 4.97% and 60.4 ± 4.83%, respectively). The change was pronounced in the nasal region (p < 0.001) and central region (p < 0.05). CT in the temporal macula increased at 1 week (239.65 ± 72.98 µm) after surgery and decreased at 1 and 3 months after surgery (222.15 ± 71.91 µm and 222.33 ± 65.72 µm, respectively; p < 0.01). CONCLUSIONS: Short-term postoperative variations in the choroid have been demonstrated in eyes with ERM. This may be related to the release of macular traction. CVI assessment using EDI-OCT may be a useful tool for investigating choroidal structural changes accompanying ERM and postoperative period.

Current state of knowledge on intelligent-response biological and other macromolecular hydrogels in biomedical engineering: A review.

Because intelligent hydrogels have good biocompatibility, a rapid response, and good degradability as well as a stimulus response mode that is rich, hydrophilic, and similar to the softness and elasticity of living tissue, they have received widespread attention and are widely used in biomedical engineering. In this article, we conduct a systematic review of the use of smart hydrogels in biomedical engineering. First, we introduce the properties and applications of hydrogels and compare the similarities and differences between traditional hydrogels and smart hydrogels. Secondly, we summarize the intelligent hydrogel types, the mechanisms of action used by different hydrogels, and the materials for preparing different types of hydrogels, such as the materials for the preparation of temperature-responsive hydrogels, which mainly include gelatin, carrageenan, agarose, amylose, etc.; summarize the morphologies of different hydrogels, such as films, fibers and microspheres; and summarize the application of smart hydrogels in biomedical engineering, such as for the delivery of proteins, antibiotics, deoxyribonucleic acid, etc. Finally, we summarize the shortcomings of current research and present future prospects for smart hydrogels. The purpose of this paper is to provide researchers engaged in related fields with a systematic review of the application of intelligent hydrogels in biomedical engineering. We hope that they will get some inspiration from this work to provide new directions for the development of related fields.

Rapid prototyping enzyme homologs to improve titer of nicotinamide mononucleotide using a strategy combining cell-free protein synthesis with split GFP.

Engineering biological systems to test new pathway variants containing different enzyme homologs is laborious and time-consuming. To tackle this challenge, a strategy was developed for rapidly prototyping enzyme homologs by combining cell-free protein synthesis (CFPS) with split green fluorescent protein (GFP). This strategy featured two main advantages: (1) dozens of enzyme homologs were parallelly produced by CFPS within hours, and (2) the expression level and activity of each homolog was determined simultaneously by using the split GFP assay. As a model, this strategy was applied to optimize a 3-step pathway for nicotinamide mononucleotide (NMN) synthesis. Ten enzyme homologs from different organisms were selected for each step. Here, the most productive homolog of each step was identified within 24 h rather than weeks or months. Finally, the titer of NMN was increased to 1213 mg/L by improving physiochemical conditions, tuning enzyme ratios and cofactor concentrations, and decreasing the feedback inhibition, which was a more than 12-fold improvement over the initial setup. This strategy would provide a promising way to accelerate design-build-test cycles for metabolic engineering to improve the production of desired products.

The effectiveness and safety of the rapid titration strategy of background controlled-release oxycodone hydrochloride for patients with moderate-to-severe cancer pain: A retrospective cohort study.

Background: Oxycodone hydrochloride is a semisynthetic narcotic analgesic agent. This study aimed to explore optimal titration strategy of controlled-release (CR) oxycodone hydrochloride in patients with cancer pain. Methods: 258 patients, who used regular strong opioids (morphine and CR oxycodone hydrochloride) for cancer pain across 25 three grade class hospitals in China during January 15th 2017 to April 30th 2017, were retrospectively studied. The patients were divided into 4 groups according to treatment regimens titrated. The pain remission rate and numeric rating scale (NRS) of cancer pain was recorded at 0, 12, 24, 36, 48, 60, 72 h after opioid titration. The incidence of adverse events (AEs) with therapy were also observed. Results: 12 h after treatment, pain remission rate of Group B, C and D was significantly higher (P < 0.001) than Group A. For the complete remission rate, there were also significant differences among the four groups (P < 0.001). No significant difference was found among four groups for pain remission rate at 24, 72 h after treatment. Multiple comparison of NRS scores showed that the both Group B and C varied significantly with Group D (P = 0.028, P = 0.05, respectively), showing superior analgesic effect over Group D. AEs were significantly different among groups (P < 0.01), with the most frequent AEs in Group A, lowest in Group B. Conclusion: The rapid titration strategy of background CR oxycodone hydrochloride was effectiveness and safety in patients with moderate-to-severe cancer pain.

Medial tibial plateau sustaining higher physiological stress than the lateral plateau: based on 3D printing and finite element method.

BACKGROUND: Medial compartment knee osteoarthritis (KOA) accounts for most KOA cases, and increased trabecular bone volume fraction (BV/TV) is one of the pathological changes in the tibial plateau of KOA. How BV/TV changes before and after the menopause and its effects on medial compartment KOA are yet to be clarified. METHODS: Twenty femurs from twenty 12-week-old rats were included. The operated group underwent ovariectomy (to represent the osteoporosis condition), called the O group, and the non-operated group was the normal control, called the N group. Micro-CT scans of the femoral condyles were acquired 12 weeks after the surgery, and the volume of interest (VOI) of medial-, inter-, and lateral-condyle trabeculae were three-dimensional (3D) printed for uniaxial compression mechanical test and simulated by the finite element (FE) method. RESULTS: The results demonstrated that the O group indicated poorer trabecular architecture than the N group in three parts of the femoral condyle, especially in the intercondyle. Within the group, the BV/TV, trabecular thickness (Tb.Th), and trabecular number (Tb.N) ratios between the medial and lateral condyles were greater than 1 in both N and O groups. The medial condyle trabeculae's mechanical properties were higher than those of the lateral condyle, and this superiority appears to be broadened under osteoporotic conditions. FE modelling well reproduced these mechanical differentiations. CONCLUSIONS: According to Wolff's law, the higher BV/TV and mechanical properties of the medial femoral condyle may be due to inherent imbalanced loading on the knee component. Alterations in BV/TV and their corresponding mechanical properties may accompany KOA.

Genetic Variation Analysis of Porcine Circovirus Type 4 in South China in 2019 to 2021.

Porcine circovirus type 4 (PCV4) is a novel virus associated with porcine dermatitis and nephropathy syndrome (PDNS)-like signs identified firstly in China in 2019. However, the details of the molecular epidemiology of PCV4 are unclear at this time. A total of forty-two related sequences were selected from the GenBank database to explore the spread of PCV4 and its rule in genetic evolution. Of the selected strains, 41 were from south China in 2019 to 2021 and the other was a foreign representative strain. Phylogenetic tree construction, nucleotide and amino acid (aa) sequence alignment, gene recombination and antigen structure prediction were performed on the collected sequences using bioinformatics softwares. The 42 PCV4 strains were divided into two subgenotypes: PCV4a (35/42) and PCV4b (7/42), according to the constructed genetic evolution tree. PCV4a is the main epidemic strain, and it can be further divided into two different gene clusters: PCV4a-1 (22/35) and PCV4a-2 (13/35). The pairwise comparison analysis showed that the complete genome sequence similarity of the 42 PCV4 strains ranged between 97.9% and 100%, and the aa sequences of the Cap proteins of 42 PCV4 strains had three major heterogenic or hypervariable regions-27-28, 96 and 212-all located near the antigenic epitope of the Cap protein. The results of this study can provide some basis for further studying the spread and epidemic growth of PCV4, and the prevention and control of PCV4 infection in China.

Construction of luminescent Escherichia coli via expressing lux operons and their application on toxicity test.

Recombinant luminescent Escherichia coli strains could be used to detect the toxicity of pure or mixed contaminants as a light-off sensor. In this work, the lux operon of Photobacterium phosphoreum T3 was identified for the first time. Recombinant luminescent E. coli strains were constructed via expressing the lux operons of P. phosphoreum T3 and Vibrio qinghaiensis Q67 in E. coli MG1655, and the optimal protectant containing 10% (w/v) trehalose and 4% sucrose was used to prepare the freeze-dried recombinant luminescent E. coli cells. Then, these freeze-dried E. coli cells were subjected to acute toxicity detection. The results showed that luminescent E. coli strains displayed sensitive toxic responses to BPA, nFe2O3, Cd, Pb, As, and Hg, for example, the EC50 values of BPA and nFe2O3 to luminescent E. coli strains ranged from 1.54 to 50.19 mg/l and 17.50 to 21.52 mg/l, respectively. Indeed, luminescent E. coli strains exhibited more sensitive responses to Cd, Pb, and Hg than the natural strain Q67. The results suggested that recombinant luminescent E. coli strains could be used for the detection of acute toxicity. Furthermore, the combined toxicities of BPA and nFe2O3, Hg, and Pb were measured, and the joint effects of these mixtures were evaluated with luminescent E. coli. The results indicated that the joint effects of BPA and nFe2O3 suggested to be synergistic or additive to luminescent E. coli, while the joint effects of heavy metals and nFe2O3 exhibited additivities. The cellular endocytosis for Fe2O3 nanoparticles was not observed, which could explain the additive instead of synergistic effects between heavy metals and nFe2O3. KEY POINTS: • Sequence of the lux operon from P. phosphoreum T3 was reported for the first time. • Recombinant luminescent E. coli was more sensitive to Cd, Pb, and Hg than Q67. • Joint effects of BPA and nFe2O3 were synergistic or additive to luminescent E. coli.

Progress in the application of sustained-release drug microspheres in tissue engineering.

Sustained-release drug-loaded microspheres provide a long-acting sustained release, with targeted and other effects. There are many types of sustained-release drug microspheres and various preparation methods, and they are easy to operate. For these reasons, they have attracted widespread interest and are widely used in tissue engineering and other fields. In this paper, we provide a systematic review of the application of sustained-release drug microspheres in tissue engineering. First, we introduce this new type of drug delivery system (sustained-release drug carriers), describe the types of sustained-release drug microspheres, and summarize the characteristics of different microspheres. Second, we summarize the preparation methods of sustained-release drug microspheres and summarize the materials required for preparing microspheres. Third, various applications of sustained-release drug microspheres in tissue engineering are summarized. Finally, we summarize the shortcomings and discuss future prospects in the development of sustained-release drug microspheres. The purpose of this paper was to provide a further systematic understanding of the application of sustained-release drug microspheres in tissue engineering for the personnel engaged in related fields and to provide inspiration and new ideas for studies in related fields.

Effects of Exercise on Optic Nerve and Macular Perfusion in Glaucoma and Normal Subjects.

PRCIS: Using optical coherence tomography angiography, we found an increase in the blood flow in regional macular without significant changes in the optic disk in patients with glaucoma after a moderate exercise regime. PURPOSE: To investigate the effect of moderate exercise on optic nerve and macular perfusion in glaucoma patients. METHODS: Overall, 25 eyes of 25 patients with primary open angle glaucoma and 22 eyes of 22 normal subjects were included in the glaucoma and control groups, respectively. Foveal avascular zone parameters, whole and regional vessel density (VD) in the superficial layer of macula, VDs in the radial peripapillary capillary layer of the optic nerve head, intraocular pressure, and cardiovascular parameters were measured using optical coherence tomography angiography before, immediately after, and 30 minutes after a 20-minute run at moderate speed. RESULTS: In the glaucoma group, macular superficial VD of the whole image, parafovea, and superior and nasal regions were higher after 30 minutes of rest (44.049±5.704, 47.238±5.741, 48.692±6.648, and 47.852±5.078) than immediately after exercise (43.229±5.867, 46.334±5.984, 47.840±6.895, 46.793±5.238, P <0.05). The VD in the temporal and nasal regions was higher 30 minutes after exercise (45.105±5.512 and 47.852±5.078) than before exercise (44.265±5.803 and 46.750±5.639, P <0.05). The intraocular pressure decreased immediately after exercise (14.20±2.51 and 14.51±2.96 mmHg for glaucoma and controls, respectively) but was restored after 30 minutes of rest (15.84±3.57 mmHg for glaucoma and 16.50±2.25 mmHg for controls) in both groups ( P <0.001). Cardiovascular parameters were similar in both groups. CONCLUSION: Moderate physical exercise for 20 minutes increased blood flow in the macula region without significant change to the optic nerve and lowered intraocular pressure in glaucoma and normal subjects. The benefit of these findings to glaucoma patients needs further study.

Characteristics of the Optic Nerve Head in Myopic Eyes Using Swept-Source Optical Coherence Tomography.

Purpose: To investigate the characteristics of the optic nerve head (ONH) in myopia using swept-source optical coherence tomography (SS-OCT). Methods: Participants were divided into three groups according to the axial length (AL). The optic disc morphology, retinal nerve fiber layer (RNFL) thickness, and radial peripapillary capillary (RPC) vessel density (VD), optic disc tilt, rotation, Bruch's membrane opening distance (BMOD), border length (BL), border tissue angle, focal lamina cribrosa (LC) defects, ß- and γ-zone peripapillary atrophy (PPA), microvasculature dropout (MvD), choroidal thickness (CT), and the choroidal vascularity index (CVI) were compared. Linear regression analysis evaluated relationships between spherical equivalent, AL, and ONH parameters. Results: One hundred five, 98, and 118 eyes were included in groups 1, 2, and 3, respectively. With AL increasing, the mean, superior and temporal CT, central mean and temporal, pericentral mean, inferior and nasal RPC VD, and temporal CVI decreased, whereas the mean and temporal RNFL thickness, optic disc, RIM and ß-PPA area, presence and area of γ-PPA, BMOD and BL increased. Compared to other groups, group 3 depicted a larger cup area, more focal LC defect and total and juxtapapillary MvD; a lower central superior, inferior and nasal, pericentral superior, and temporal RPC VD. Group 1 demonstrated more tilted disc, larger inferior and nasal CT, mean, superior, inferior, and nasal CVI. Conclusions: Myopia eyes have larger ONH changes, PPAs, regional RNFL, and MvD, but smaller regional CTs, RPC VD, and CVIs. SS-OCT may be useful in detecting ONH variations during myopia.

Choroidal Vascularity Index Changes After Exercise in Patients With Glaucoma.

Purpose: To investigate the changes in choroidal vascular structures after exercise in patients with glaucoma using an image binarisation algorithm with enhanced-depth imaging optical coherence tomography. Methods: Thirty-four eyes of 19 patients with primary open-angle glaucoma and 40 eyes of 20 normal subjects were included in the glaucoma and control groups, respectively. All subjects were evaluated before, immediately after, and 30 min after 20-min running at moderate speed. The subfoveal choroidal area was segmented into the luminal area (LA) and stromal area (SA), and the choroidal vascularity index (CVI) was measured by calculating the ratio of LA to the total choroidal area (TCA). The mean intraocular pressure (IOP), subfoveal choroidal thickness, CVI, SA, CA, and TCA were compared within and between both groups. The correlation between CVI, IOP, and other vascular indexes was investigated. Results: In the glaucoma group, a significantly lower CVI was found immediately after exercise and recovered 30 min after exercise. Higher TCA and LA levels were demonstrated 30 min after exercise compared to immediately after exercise. In both groups, IOP decreased immediately after exercise but was restored after a 30-min rest. In the glaucoma group, there was a higher correlation between CVI and other choroidal vascular parameters than in the control group. There was no difference in IOP or choroidal parameters between the groups at different time points. Conclusion: In patients with glaucoma, CVI decreased significantly immediately after exercise, indicating that the choroidal layer is affected by exercise and an unhealthy vascular regulatory mechanism.

Characteristics of macular microvasculature before and after idiopathic macular hole surgery.

AIM: To evaluate the macular microvasculature before and after surgery for idiopathic macular hole (MH) and the association of preoperative vascular parameters with postoperative recovery of visual acuity and configuration. METHODS: Twenty eyes from 20 patients with idiopathic MH were enrolled. Optical coherence tomography angiography (OCTA) images were obtained before, 2wk, 1, and 3mo after vitrectomy with internal limiting membrane peeling. Preoperative foveal avascular zone (FAZ) area and perimeter and regional vessel density (VD) in both layers were compared according to the 3-month best-corrected visual acuity (BCVA). RESULTS: The BCVA improved from 0.98±0.59 (logMAR, Snellen 20/200) preoperatively to 0.30±0.25 (Snellen 20/40) at 3mo postoperatively. The preoperative deep VD was smaller and the FAZ perimeter was larger in the 3-month BCVA<20/32 group (all P<0.05). A significant reduction was observed in FAZ parameters and all VDs 2wk postoperatively. Except for deep perifoveal VD, all VDs recovered only to their preoperative values. The postoperative FAZ parameters were lower during follow-up. Decreases in preoperative deep VDs were correlated with worse postoperative BCVA (Pearson's r=-0.667 and -0.619, respectively). A larger FAZ perimeter (Spearman's r=-0.524) and a lower deep perifoveal VD preoperatively (Pearson's r=0.486) were associated with lower healing stage. CONCLUSION: The status of the deep vasculature may be an indicator of visual acuity in patients with a closed MH. Except for the deep perifoveal region, VD recovers only to preoperative levels.

Anlotinib Monotherapy for Refractory Metastatic Colorectal Cancer: A Double-Blinded, Placebo-Controlled, Randomized Phase III Trial (ALTER0703).

BACKGROUND: Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC. MATERIALS AND METHODS: This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1-14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety. RESULTS: A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4-4.5) over placebo group (1.5 months; 95% CI, 1.4-1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27-0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8-9.7 vs. 7.2 months; 95% CI, 6.2-8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%). CONCLUSION: Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients. IMPLICATIONS FOR PRACTICE: In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.

Transition element doped octahedral manganese molecular sieves (Me-OMS-2) as diclofenac adsorbents.

Diclofenac (DCF) control measures have become an area of increased interest for environmental researchers due to the high environmental concentration and risk of DCF. Adsorption seems to be promising for DCF removal from the aqueous phase because of its specific superiority in comparison with biodegradation, membrane separation, and advanced oxidation or reduction. In this study, OMS-2 and metal-doped OMS-2 ((Me-OMS-2, with Me = Co, Cu or Ce) were prepared and tested as adsorbents for the removal of DCF. It was evident that the maximum adsorption capacity and rate of Ce-OMS-2 were much higher than those of the other adsorbents, which could be attributed to its large specific surface area and stereoscopic aperture structure. The experimental data are fitted the pseudo-second-order model, the Elovich equation and the Langmuir model well; moreover, the process is an endothermic and spontaneous thermodynamic process, during which the entropy increased, based on the experimental results, indicating that chemisorption was dominant during the DCF adsorption process onto Ce-OMS-2. By the integral of the peak deconvoluted from the XPS spectrum, the ratio of Mn3+/Mn4+ increased from 0.393 to 0.407, revealing that Mn(IV) is rarely reduced into Mn(III) during the DCF adsorption process.

HS-GC-IMS-Based metabonomics study of Baihe Jizihuang Tang in a rat model of chronic unpredictable mild stress.

The aim of this study was to investigate the differences in volatile organic compounds (VOCs) obtained from the feces of a Baihe Jizihuang Tang (BHT)-treated rat depression model. Rats were subjected to chronic unpredictable mild stress (CUMS), and the differences in VOCs were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), NIST software, principal component analysis, and orthogonal partial least squares discriminant analysis. Eleven biomarkers were identified on the basis of VOC migration time, and their relative peak intensities were analyzed. A metabonomic model was established using multivariate statistical analysis. The study demonstrated the metabonomics of CUMS rats and the intervention effect of BHT and also highlighted the potential therapeutic effects of the traditional Chinese medicine (TCM) Jingfang for the clinical treatment of complex diseases, which was in line with the holistic and systemic approaches of TCM. This study augments the use of metabonomics based on HS-GC-IMS in research studies. Using this method, there is no need to pre-process samples by extraction or derivatization, and the VOC component of the sample can be detected directly and rapidly. In conclusion, this study establishes a simple, convenient, and fast technique, which can help identify clinical biomarkers for rapid medical diagnosis.

Cobalt tetracarboxyl phthalocyanine-manganese octahedral molecular sieve (OMS-2) as a heterogeneous catalyst of peroxymonosulfate for degradation of diclofenac.

A composite of cobalt tetracarboxyl phthalocyanine and amino-functionalized manganese octahedral molecular sieve (CNOMS-2) was synthesized in a simple way, and applied for degrading diclofenac in aqueous media by catalyzing of peroxymonosulfate heterogeneously. The experiment results revealed that the CNOMS-2/PMS system was highly efficient for DCF degradation in the pH range of 5-9, and the mechanism involved the generation of OH, SO4⁻ and 1O2 by the activation of PMS. The main reactive oxygen species was found to be 1O2 by radical scavenging experiments and electron paramagnetic resonance (EPR) spectroscopy. Further, a carboxylation product of DCF at m/z 340 was found to be a prominent intermediate of the reaction in this system specially, as determined by LC-MS/MS. The reusability and ion leaching concentrations under different pH were also examined to determine the application prospects of the catalyst.