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Mitochondrial quality control (MQC) mechanisms are a series of adaptive responses that ensure the relative stability of mitochondrial morphology, quantity, and quality to preserve cellular survival and function. While MQC mechanisms range from mitochondrial biogenesis and fusion/fission to mitophagy, mitochondrial-derived vesicles (MDVs) may represent an essential component of MQC. MDVs precede mitochondrial autophagy and serve as the first line of defense against oxidative stress by selectively transferring damaged mitochondrial substances to the lysosome for degradation. In fact, the function of MDVs is dependent on the cargo, the shuttle route, and the ultimate destination. Abnormal MDVs disrupt metabolite clearance and the immune response, predisposing to pathological conditions, including neurodegeneration, cardiovascular diseases, and cancers. Therefore, MDV regulation may be a potential therapeutic for the therapy of these diseases. In this review, we highlight recent advances in the study of MDVs and their misregulation in various diseases from the perspectives of formation, cargo selection, regulation, and transportation.

Background Migraine is a complex disorder characterized by debilitating headaches. Despite its prevalence, its pathophysiology remains unknown, with subsequent gaps in diagnosis and treatment. We combined machine learning with connectivity analysis and applied a whole-brain network approach to identify potential targets for migraine diagnosis and treatment. Methods Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI(rfMRI), and diffusion weighted scans were obtained from 31 patients with migraine, and 17 controls. A recently developed machine learning technique, Hollow Tree Super (HoTS) was used to classify subjects into diagnostic groups based on functional connectivity (FC) and derive networks and parcels contributing to the model. PageRank centrality analysis was also performed on the structural connectome to identify changes in hubness. Results Our model attained an area under the receiver operating characteristic curve (AUC-ROC) of 0.68, which rose to 0.86 following hyperparameter tuning. FC of the language network was most predictive of the model’s classification, though patients with migraine also demonstrated differences in the accessory language, visual and medial temporal regions. Several analogous regions in the right hemisphere demonstrated changes in PageRank centrality, suggesting possible compensation. Conclusions Although our small sample size demands caution, our preliminary findings demonstrate the utility of our method in providing a network-based perspective to diagnosis and treatment of migraine.

Dissolving microneedles (MNs) have emerged as a promising transdermal delivery system, as they integrate the advantages of both injection and transdermal preparations. However, the low drug-loading and limited transdermal delivery efficiency of MNs severely hinder their clinical applications. Microparticle-embedded gas-propelled MNs were developed to simultaneously improve drug-loading and transdermal delivery efficiency. The effects of mold production technologies, micromolding technologies, and formulation parameters on the quality of gas-propelled MNs were systematically studied. Three-dimensional printing technology was found to prepare male mold with the highest accuracy, while female mold made from the silica gel with smaller Shore hardness could obtain a higher demolding needle percentage (DNP). Vacuum micromolding with optimized pressure was superior to centrifugation micromolding in preparing gas-propelled MNs with significantly improved DNP and morphology. Moreover, the gas-propelled MNs could achieve the highest DNP and intact needles by selecting polyvinylpyrrolidone K30 (PVP K30), polyvinyl alcohol (PVA), and potassium carbonate (K2CO3): citric acid (CA) = 0.15:0.15 (w/w) as the needle skeleton material, drug particle carrier, and pneumatic initiators, respectively. Moreover, the gas-propelled MNs showed a 1.35-fold drug loading of the free drug-loaded MNs and 1.19-fold cumulative transdermal permeability of the passive MNs. Therefore, this study provides detailed guidance for preparing MNs with high productivity, drug loading, and delivery efficiency.

5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) has emerged as a promising therapy for hypertrophic scar (HS). However, the poor permeability of ALA across biological barriers and pro-survival autophagy of fibroblasts largely restricted the efficacy of PDT. Herein, PDT was well equipped with spear and shear to overcome the therapeutic resistance. Specifically, hyaluronidase (HAase) based dissolving microneedles (MN)with improved stiffness and permeability were developed as a spear to deliver ALA into deep lesions by combating the dual barriers of stratum corneum and dense extracellular matrix (ECM). Besides, metformin (Met) MN was applied as a shear to intervene the respiration and autophagic process for amplified PDT. HAase significantly enhanced the in vitro and in vivo transdermal delivery efficiency of ALA, while the combination of HAase and Met successfully amplified the anti-scarring efficacy of PDT by elevating cytotoxicity, promoting permeation, activating signal pathways, and interdicting the autophagy process simultaneously. The pharmacodynamics study revealed that the combination therapy achieved the lowest scar elevation index (SEI), downregulated expression of collagen I and TGF-β1, and decreased LC3 II/I ratio, showing excellent therapeutic efficacy. Therefore, such a fully armed PDT integrating double-prolonged attack on the physiological and pathological barriers offers a promising topical treatment for deep HS.

Rheumatoid arthritis (RA) is a perennial inflammatory condition. Preliminary research indicated that long non-coding (lnc)RNA cancer susceptibility candidate 2 (CASC2) was downregulated in the serum of RA patients. Our study was designed to reveal the roles of lncRNA CASC2 in RA and the latent mechanisms underlying its role. Bioinformatics method (Starbase) and dual-luciferase reporter assay revealed that microRNA (miR)-18a-5p directly interacted with lncRNA CASC2. Furthermore, lncRNA CASC2 and miR-18a-5p expression in the serum samples of RA patients and healthy controls were measured via reverse transcription-quantitative PCR. Compared with the healthy subjects, lncRNA CASC2 was downregulated, whereas miR-18a-5p was upregulated in patients with RA. Overexpression of lncRNA CASC2 decreased the viability of human fibroblast-like synoviocytes (HFLSs) and induced apoptosis, as revealed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry analyses. Furthermore, the Western blotting assay suggested that Bax was upregulated and Bcl-2 was downregulated in lncRNA CASC2 up-regulated HFLSs. Downregulation of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)1, and MMP3 levels by lncRNA CASC2 up-regulation was determined using enzyme-linked immunosorbent assays (ELISAs). However, HFLSs co-transfected with miR-18a-5p mimic exhibited opposite effects compared with the case for the overexpression of lncRNA CASC2. The aforementioned methods were used to verify that a binding site exists between B-cell translocation gene 3 (BTG3) and miR-18a-5p. The effects of miR-18a-5p inhibitor on HFLSs were reversed by BTG3 silencing. Overall, lncRNA CASC2 alleviated RA by adjusting the miR-18a-5p/BTG3 signaling axis and could serve as a novel therapeutic option for RA.

The long-term effect of botulinum neurotoxin A (BoNT-A) on children with cerebral palsy (CP) is unclear, and how the dynamic changes of metabolites impact the duration of effect remains unknown. To tackle this, we collected 120 plasma samples from 91 children with spastic CP for analysis, with 30 samples in each time point: prior to injection and 1, 3, and 6 months after injection. A total of 354 metabolites were identified across all the time points, 39 of which exhibited significant changes (with tentative IDs) (

Background The majority of HBeAg-positive mothers with chronic hepatitis B have high levels of viremia and inactive disease with normal alanine aminotransferase (ALT) during pregnancy. In addition, postpartum disease activation and ALT flare have been reported in the range of 15% − 35%. However, the current International Association Guidelines have not provided clear recommendations and a risk-stratified monitoring schedule. Furthermore, data are lacking on the definition of normal ALT in the postpartum period in mothers with chronic hepatitis B. The clinical features and ALT flare patterns in HBeAg-positive mothers versus HBeAg-negative mothers are not fully explored. Thus, we design a cohort study to investigate the aforementioned area and generate data to assist healthcare providers in the better management of mothers with hepatitis B. Method This study is a single-center and prospective cohort study (n = 360) that consists of two groups of patients including HBsAg-positive mothers (n = 120) and healthy mothers without HBV infections (n = 240). In HBeAg-positive mothers, antiviral therapy during late pregnancy is permitted for the prevention of MTCT but discontinued at delivery if no further indication for the treatment. Mothers are enrolled at the gestational weeks of 12–24. After delivery, both mothers and their infants will be followed up until postpartum week 24. Clinical and laboratory data are collected every 4 weeks during the study except there are no follow-up visits at the postpartum weeks 16 and 20. The primary assessment is the proportion of patients with postpartum ALT flares. The secondary assessments are independent risk factors during pregnancy for predicting postpartum ALT flares and the normal range of postpartum ALT levels in healthy mothers. Discussion We will assess the incidence of postpartum ALT flares in mothers with chronic hepatitis B with subgroup analysis based on HBeAg status, and evaluate the normal range of postpartum ALT in healthy mothers without hepatitis B. In mothers with hepatitis B, the independent risk factors for predicting postpartum ALT flares are also investigated. Trial Registration Number at the Chinese Clinical Trial Registry: ChiCTR2200061130

PurposeTo describe a new technique for repairing wide iridodialysis (>180°) with a double-armed flanged polypropylene suture.SettingPrivate practice, Wuhan, China.DesignCase report.MethodsAdjacent to the iridodialysis side, the sclera was punctured 2 mm exterior to the corneal limbus into the anterior chamber with a 30-G needle, then the root of the de-inserted iris was punctured. A 7-0 polypropylene thread was placed into the anterior chamber through a corneal incision on the opposite side and inserted into the needle. The needle was withdrawn, leaving one side of the suture out of the eye. Then, the sclera was punctured by a new needle 2 mm from the first puncture site and passed through the iris root 2 mm from the original iris puncture point. The other end of the thread was inserted into the needle and taken out of the eye. The suture was tightened to make the iris root adhere to the corneal limbus. Finally, the suture is was cut, and the ends were cauterized and left inside the sclera. This procedure can be repeated until the iridodialysis is solved.ResultsThe abovementioned technique was applied in four cases. At the end of the operations, the pupils of all patients were nearly round, with a diameter of about 3 mm. No patient suffered from intraoperative and postoperative complications.ConclusionsThe double-armed flanged polypropylene suture is a simple and safe operation method that can be applied to repair wide iridodialysis.

Azithromycin (AZI) is a commonly used antibiotic with extremely bitter taste that severely decreases the compliance of patients. Besides, the poor solubility of AZI in alkaline pH makes it difficult to be absorbed in the small intestine. To achieve the dual effects of taste masking and enhanced absorption, AZI-loaded pellets were coated by polymer blend of Eudragit®RL30D and Eudragit®L30D-55. The coated pellets could avoid drug release in the oral environment (pH 5-7) but release rapidly in the gastric environment (pH 1-3). Then, the coated pellets were further formulated into dry suspension to address the problem of dysphagia. The taste-masking effect tests by electronic tongue and human volunteers revealed that the dry suspension was more effective to improve the bitter taste of AZI than the commercial product. Therefore, this study provided an economical and feasible approach for taste masking with good practical application prospect.

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors., Graphical abstract Dissolving microneedles encapsulating TPGS/HA functionalized PLGA nanoparticles provide a highly efficient local treatment for superficial tumor by integrating chemotherapy and photothermal therapy (PTT). The functionalized nanoparticles significantly enhanced the cytotoxicity, and sensitized tumor cells toward chemotherapy through multiple pathways.Image 1

PurposeThis study aimed to investigate the clinical presentation of acute primary angle closure (APAC) during the COVID-19 epidemic lockdown in Wuhan.MethodsConsecutive patients seeking APAC treatment at the Wuhan Aier Eye Hospital during the 76 days (January 23–April 8, 2020) when the lockdown policy was implemented due to the COVID-19 pandemic were compared to those during the same period the following year (January 23–April 8, 2021), when the lockdown policy was not implemented. The cohorts were compared to assess demographic variables and clinical presentations.ResultsA total of 54 patients (64 eyes) were included in the 2020, compared with 46 patients (51 eyes) in the 2021. Demographic factors were similar between the groups. Significantly more patients developed blindness in the 2020 cohort (21.87%) than in the 2021 cohort (7.84%). Patients in the 2020 showed a longer time from symptom to treatment (241.84 ± 211.95 h in 2020 vs. 121.53 ± 96.12 h in 2021; P = 0.001), higher intraocular pressure at presentation (52.63 ± 12.45 mmHg in 2020 vs. 45.16 ± 9.79 mmHg in 2021; P = 0.001), larger pupil diameter (5.47 ± 1.62 mm in 2020 vs. 4.33 ± 1.27 mm in 2021; P = 0.001), and more glaucomatous optic neuropathy diagnoses [20/64 eyes (31.25%) in 2020 vs. 7/51 eyes (13.73%) in 2021; P = 0.03].ConclusionThe time between the onset of APAC symptoms and its treatment during the COVID-19 epidemic lockdown was significantly prolonged, which increased the blindness rate of APAC patients.

Microneedles (MNs) with enhanced delivery efficiency have revolutionized the transdermal drug delivery system for treating systemic illness. However, the bioavailability of MNs was still far from the clinical requirements by only overcoming the stratum corneum barrier. Herein, hyaluronidase (HAase)-powered MNs were developed as a top-down permeation-enhancement strategy to hijack the sequential transdermal barriers for improved bioavailability. HAase MNs with robust mechanical strength showed excellent skin penetration ability and significantly enhanced the transdermal delivery efficacy of macromolecular drugs as compared to that of HAase-absent MNs, resulting in considerable effect to subcutaneous injection in terms of biodistribution, bioavailability, and therapeutical efficacy. As evidenced from the distribution of trypan blue and fluorescence underlying skin, the positive effects exerted by HAase MNs could be ascribed to the depolymerization of HA that would loosen the subcutaneous space and destruct the extracellular matrix barrier to promote drug diffusion and permeation in larger area and greater depth. Notably, the transient interconversion of keratin from α-helix to β-sheet that might assist the drug residues on the skin surface permeate across the stratum corneum during administration might be another reason not to be ignored. As a labor-saving strategy, HAase-powered MNs offers a promising and painless administration route for macromolecules.

AimTo investigate the efficacy and safety of high-calorie formula vs. Chinese daily food on the nutritional status and motor function of undernourished children with cerebral palsy (CP).MethodsIn this prospective, assessor-blind, and randomized controlled trial, we recruited children (1–10 years) with CP and undernutrition based on the WHO and the American Society for Parenteral and Enteral Nutrition criteria from the National Children's Medical Center. Participants were randomly allocated (1:1) to a high-calorie formula group or a Chinese daily food diet group (control group) for 6 months. Indirect calorimetry was used to estimate energy requirements. We compared the nutritional status and gross motor function of participants in both groups based on weight, height, z-scores (weight-for-age, height-for-age, weight-for-height, and BMI-for-age), and the Gross Motor Function Measure (GMFM), respectively, at baseline, 3-, and 6-months follow-up. In addition, the effective rate of nutritional intervention, and adverse events were simultaneously assessed.ResultsFrom July 2020 to December 2021, a total of 119 participants were enrolled and randomized, and 110 participants completed the study (with 54 children in the high-calorie formula group and 56 children in the control group). After 6 months of treatment, the weight, height, z-scores (weight-for-height, weight-for-age, and BMI-for-age), and GMFM of both groups were significantly improved (p < 0.05). There were significant differences in changes in weight, weight-for-age z-scores, and GMFM between the two groups (p < 0.05). During the study period, 16 children experienced at least one mild adverse event [9 (16.7%) in the formula group and 7 (12.5%) in the control group].ConclusionNutritional intervention with a high-calorie formula may be an effective and safe option in children with CP for improving undernutrition and gross motor dysfunction.Clinical trial registrationwww.chictr.org.cn, identifier: ChiCTR2000033878.

To compare the risks of adverse events 3 months after Onabotulinumtoxin-A and Lanbotulinumtoxin-A injections in children with cerebral palsy (CP) and to identify risk factors and associations.A total of 1037 children (682 males, 355 females; mean age 5 years 2 months [SD 3 years]; age range 2 years-17 years 10 months) with CP underwent 1013 Onabotulinumtoxin-A injections and 418 Lanbotulinumtoxin-A injections from 2012 to 2021. Information was recorded in a purpose-built database.The adverse event rates of Onabotulinumtoxin-A and Lanbotulinumtoxin-A were reported as 13.92% and 11.96% respectively. Most adverse events were mild and self-limiting. Children in Gross Motor Function Classification System (GMFCS) levels IV to V had a higher risk of adverse events than those in GMFCS levels I to III (odds ratio [OR] [95% confidence interval {CI}] = 3.65 [1.56, 5.40], p 0.01). The history of recent illness and higher dose increased the likelihood of adverse events (OR [95% CI] = 2.00 [1.55, 3.00] and 2.20 [1.53, 3.07] respectively, p 0.01). Sex, age, and the number of injections had no significant effect on adverse event rates (p 0.05). The incidence of upper respiratory tract infection and lower respiratory tract infection after injections was weakly correlated with the incidence before injections (r = 0.36 and r = 0.27 respectively, p 0.01).Occurrence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with CP. Dose, GMFCS level, and health background were risk factors.The prevalence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with cerebral palsy (CP). The prevalence of adverse events increased with the severity of CP and the injected dose. Sex, age, and number of injections had no significant effect on the prevalence of adverse events.

A facile and effective multifunctional platform with high bacterial detection sensitivity, good antibacterial activity, and excellent dye decomposition efficiency holds great promise for wastewater treatment. To explore the design rationality and mechanism of material platforms with various integrated components into a single molecule for wastewater treatment applications, herein, four kinds of polyelectrolyte photosensitizers with aggregation-induced emission (AIE) fluorescent units are synthesized and systematically studied to investigate the structure-property relationship that influences the level of conjugation and the hydrophobicity-hydrophilicity balance. By improving the strength of the conjugation, the new AIE photosensitizers DBPVEs (including DBPVE-4 and DBPVE-6) generate a reactive oxygen species (ROS), and a decomposition efficiency of around 55% is obtained for dyes when they are exposed to DBPVEs under white light irradiation, which is higher than those of DBPEs (including DBPE-4 and DBPE-6). More importantly, owing to the longer and more flexible aliphatic chains of DBPVE-6 that facilitate efficient intercalation into cell membranes, the staining ability of DBPVE-6 for methicillin-resistant S. epidermidis (MRSE) is greatly enhanced as compared to that of DBPVE-4. It should be noted that the antibacterial experiment indicates that DBPVE-6 displays potent toxicity to MRSE with 99.9% killing efficiency under white light irradiation. This work provides essential theoretical and experimental guidance on the designing of new photosensitizers for wastewater treatment.

Osteoarthritis (OA) is a chronic joint disease with occurrence of articular inflammation and cartilage degeneration. An ideal drug delivery system for effective treatment of OA should integrate inflammation alleviation with cartilage protection. Herein, a lyotropic liquid crystal (LLC) precursor co-loading hyaluronic acid (HA) and celecoxib, formulated as the HLC precursor, was developed for the combined therapeutic efficacy. The in situ gelling property of the HLC precursor effectively prolongs drug retention in the articular cavity to achieve a long-term anti-inflammation effect. Based on the rheological tests, HLC gel with a cubic lattice structure endows it with a spring-like effect to buffer joint shock and shows great potential in providing cartilage protection by resisting mechanical destruction, lubricating joint, and decomposing intensive stress (about 50%). Meanwhile, the pharmacodynamics study on the OA-induced SD rats demonstrated that HLC gel was the most effective to reduce inflammation levels and to protect the cartilage against abrasion and degeneration. Furthermore, the in vivo degradation behavior and the intra-articular irritation results of LLC/HLC gel demonstrated that it was biodegradable and biocompatible. These results collectively demonstrated that HLC gel with anti-inflammation and cartilage protection performance provides a useful approach to treat OA.

Constraint-induced movement therapy (CIMT) combined with repetitive transcranial magnetic stimulation (rTMS) have shown great potential in improving function in schoolchildren with unilateral cerebral palsy attributed to perinatal stroke. However, the prospect of application in preschool children with unilateral cerebral palsy (UCP) attributed to various brain disorders remains unclear. In this prospective, assessor-blinded, randomized controlled study, 40 preschool children with UCP (aged 2.5–6 years) were randomized to receive 10 days of CIMT combined with active or sham rTMS. Assessments were performed at baseline, 2 weeks, and 6 months post-intervention to investigate upper limb extremity, social life ability, and perceived changes by parents and motor-evoked potentials. Overall, 35 participants completed the trial. The CIMT plus active stimulation group had greater gains in the affected hand function (range of motion, accuracy, and fluency) than the CIMT plus sham stimulation group (P < 0.05), but there was no significant difference in muscular tone, social life ability, and perceived changes by parents between the two groups (P > 0.05). In addition, there was no significant difference in hand function between children with and without motor-evoked potential (P > 0.05). No participants reported severe adverse events during the study session. In short, the treatment of CIMT combined with rTMS is safe and feasible for preschool children with UCP attributed to various brain disorders. Randomized controlled studies with large samples and long-term effects are warranted.

BackgroundExercise is one of the effective ways to improve cognition. Different forms of exercises, such as aerobic exercise, resistance exercise, and coordination exercise, have different effects on the improvement of cognitive impairment. In recent years, exergames based on Non-Immersive Virtual Reality (NIVR-Exergames) have been widely used in entertainment and have gradually been applied to clinical rehabilitation. However, the mechanism of NIVR-Exergames on improving motor cognition has not been clarified. Therefore, the aim of this study is to find whether NIVR-Exergames result in a better neural response mechanism to improve the area of the cerebral cortex related to motor cognition under functional near-infrared spectroscopy (fNIRS) dynamic monitoring in comparison with resistance exercise (resistance band stretching).MethodsA cross-over study design was adopted in this study, and 15 healthy young subjects (18–24 years old) were randomly divided into group A (n = 8) and group B (n = 7) according to a computerized digital table method. Task 1 was an NIVR-Exergame task, and Task 2 was resistance band stretching. Group A first performed Task 1, rested for 30 min (i.e., a washout period), and then performed Task 2. Group B had the reverse order. The fNIRS test was synchronized in real time during exercise tasks, and heart rate measurements, blood pressure measurements, and 2-back task synchronization fNIRS tests were performed at baseline, Post-task 1, and Post-task 2. The primary outcomes were beta values from the general linear model (GLM) in different regions of interest (ROIs), and the secondary outcomes were heart rate, blood pressure, reaction time of 2-back, and accuracy rate of 2-back.ResultsThe activation differences of Task 1 and Task 2 in the right premotor cortex (PMC) (P = 0.025) and the left PMC (P = 0.011) were statistically significant. There were statistically significant differences in the activation of the right supplementary motor area (SMA) (P = 0.007), left dorsolateral prefrontal cortex (DLPFC) (P = 0.031), left and right PMC (P = 0.005; P = 0.002) between baseline and Post-task 1. The differences in systolic pressure (SBP) between the two groups at three time points among women were statistically significant (P1 = 0.009, P2 < 0.001, P3 = 0.044).ConclusionIn this study, we found that NIVR-Exergames combined with motor and challenging cognitive tasks can promote the activation of SMA, PMC and DLPFC in healthy young people compared with resistance exercise alone, providing compelling preliminary evidence of the power for the rehabilitation of motor and cognitive function in patients with central nervous system diseases.

Purpose: Reading speed in intermittent exotropia (IXT) children has been minimally examined. We assessed reading speed in school-age children with IXT and determined clinical characteristics of IXT that impacted their reading ability.Methods: A total of 63 school-age (10-16 years) children with intermittent exotropia and a group of 44 age-matched normal children were recruited. All children underwent ophthalmologic and binocular function evaluations. Reading speed was assessed with the International Reading Speed Texts (IReST). We compared reading speed of children with IXT to that of normal counterparts. In addition, the correlation between reading speed and clinical characteristics of IXT (i.e., angle of deviation, binocular function, fusion control) were evaluated.Results: Reading speed in children with IXT (231 ± 51 CPM) was much slower than their normal counterparts (257 ± 33 CPM, p=0.002). For further analysis, we divided the group of IXT patients into slow and non-slow reading groups. The average reading speed in the Slow group was significantly slower than that in the Non-slow group (158±25 CPM vs. 250±37 CPM, p < 0.001). After adjusting for the age and gender, we found a significant correlation between the LogTNO and reading speed in IXT group (r=-0.244, p=0.054). Age, gender and LogTNO were found to be factors associated with reading speed in children with IXT based on a generalized linear model. Conclusion: Our finding suggests that reading speed was slower in school-age children with IXT assessed with the International Reading Speed Texts. When age and gender were adjusted, poor stereo function at near was found to be related with a slower reading speed, and the stereoacuity at near was found to be associated with reading speed in children with IXT.

Purpose. To evaluate whether clinical measures of postoperative binocular functions could predict the long-term stability of postoperative ocular alignment in children with intermittent exotropia.Methods. A retrospective study was performed in thirty-nine children (median: 7 years) who have been surgically treated from intermittent exotropia without overcorrection (less than 10 prism diopters [pd] of exodeviation at 1 month postoperatively). Angles of deviation and binocular functions were measured preoperatively and at 1 month, 6 months, and the final follow-up visit (≥24 months) postoperatively. We examined the relationships between postoperative drift (change of ocular alignment) and binocular functions (sensory fusion, fusional convergence amplitude, and stereoacuity).Results. The surgical success rate (esophoria/tropia ≤5 pd to exophoria/tropia ≤10 pd) dropped to 76.9% at 6 months after surgery and to 53.8% at individuals’ last visit (mean: 37 months). The mean exodrift was 7.7 ± 9.2 pd from the postoperative month 1 to the final visit (p<0.001) on distance fixation. Distance stereoacuity, central fusion, and fusional convergence amplitude significantly improved following surgery (p<0.05). However, no significant correlation was found between their binocular functions measured at the beginning of each follow-up period and the postoperative drift (allp>0.13).Conclusion. Our findings suggest that the clinical measures of sensory fusion, fusional convergence amplitude, and stereoacuity cannot serve as a robust predictor for the long-term stability of postoperative ocular alignment in patients who underwent successful surgery without overcorrection at 1 month postoperatively.

Zielsetzung: Untersuchung, ob klinische Variablen der postoperativen Binokularfunktion die langfristige Stabilität der postoperativen Augenstellung nach Korrektur einer intermittierenden Exotropie bei Kindern vorhersagen können. Methode: Es erfolgte eine retrospektive Studie zu 39 Kindern (medianes Alter: 7 Jahre), die wegen einer intermittierenden Exotropie operativ behandelt worden waren und bei denen keine Überkorrektur erfolgt war (weniger als 10 Prismen-Dioptrien (PDPT) Exodeviation 1 Monat nach der Operation). Präoperativ sowie 1 Monat und 6 Monate nach der Operation und bei der letzten Nachuntersuchung (≥24 Monate) des Patienten wurden die Schielwinkel und Variablen der Binokularfunktion bestimmt. Wir untersuchten die Beziehung zwischen postoperativer Drift (Änderung der Augenstellung) und Variablen der Binokularfunktion (sensorische Funktion, konvergente Fusionsbreite und Stereosehschärfe). Ergebnisse: Die Erfolgsrate der Operation (Esophorie/-tropie ≤5 PDPT bis Exophorie/-tropie ≤10 PDPT) hatte 6 Monate nach der Operation auf 76,9% und zum Zeitpunkt der letzten Nachuntersuchungen der Patienten (im Mittel nach 37 Monaten) auf 53,8% abgenommen. Die mittlere Exodrift betrug zwischen 1 Monat nach der Operation und der letzten Nachuntersuchung bei Fernfixation 7,7 ± 9,2 PDPT (p < 0,001). Die Stereosehschärfe in der Ferne, die zentrale Fusion und die konvergente Fusionsbreite verbesserten sich nach der Operation signifikant (p < 0,05). Allerdings wurde keine signifikante Korrelation zwischen den Binokularfunktionen zu Beginn jeder Nachbeobachtungsphase und der postoperativen Drift beobachtet (alle p > 0,13). Schlussfolgerung: Unsere Beobachtungen weisen darauf hin, dass die klinischen Variablen sensorische Fusion, konvergente Fusionsbreite und Stereosehschärfe bei erfolgreich operierten Patienten, die 1 Monat nach der Operation keine Überkorrektur zeigen, nicht als robuste Prädiktoren für die langfristige Stabilität der postoperativen, korrigierten Augenstellung geeignet sind.

Cerebral palsy (CP) is a motor and postural disorder syndrome caused by the nonprogressive dysfunction of the developing brain. Previous studies strongly indicated that the Nogo-A gene might be related to the pathogenesis of CP. The objective of this research was to explore the relationship between Nogo-A polymorphisms (rs1012603, rs12464595, and rs2864052) and CP in Southern China. The Hardy-Weinberg equilibrium (HWE) testing, allele and genotype frequencies analysis, and haplotype association analysis were applied to the genotyping of 592 CP children and 600 controls. The results showed that the allele and genotype frequencies of rs1012603 of CP group were significantly different from the control group. The haplotype “TTGGG” was significantly associated with an increased risk of CP. The allele frequencies of rs1012603 were significant differences between CP with spastic diplegia, female CP cases, and controls. Furthermore, significant differences in allele and genotype frequencies were also noticed between GMFCS I of CP and controls for rs1012603, and significant differences in allele and genotype frequencies were observed between the ADL (>9) of CP and controls for rs1012603 and rs12464595. This study showed that the SNPs rs1012603 of Nogo-A were significantly correlated with CP, and the correlations were also found in spastic diplegia, GMFCS I of CP, ADL (>9) of CP, and female subgroups, indicating that Nogo-A might mainly affect mild types of CP and there might be sex-related differences.

Objective: To observe the characteristics of brain fMRI during olfactory stimulation in patients with neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS), compare the differences of brain functional activation areas between patients with NMOSD and MS, and explore the characteristics of olfactory-related brain networks of NMOSD and MS.Methods: Nineteen patients with NMOSD and 16 patients with MS who met the diagnostic criteria were recruited, and 19 healthy controls matched by sex and age were recruited. The olfactory function of all participants was assessed using the visual analog scale (VAS). Olfactory stimulation was alternately performed using a volatile body (lavender and rose solution) and the difference in brain activation was evaluated by task-taste fMRI scanning simultaneously.Results: Activation intensity was weaker in the NMOSD group than in the healthy controls, including the left rectus, right superior temporal gyrus, and left cuneus. The activation intensity was stronger for the NMOSD than the controls in the left insula and left middle frontal gyrus (P < 0.05). Activation intensity was weaker in the MS group than the healthy controls in the bilateral hippocampus, right parahippocampal gyrus, right insula, left rectus gyrus, and right precentral gyrus, and stronger in the left paracentral lobule among the MS than the controls (P < 0.05). Compared with the MS group, activation intensity in the NMOSD group was weaker in the right superior temporal gyrus and left paracentral lobule, while it was stronger among the NMOSD group in the bilateral insula, bilateral hippocampus, bilateral parahippocampal gyrus, left inferior orbital gyrus, left superior temporal gyrus, left putamen, and left middle frontal gyrus (P < 0.05).Conclusion: Olfactory-related brain networks are altered in both patients, and there are differences between their olfactory-related brain networks. It may provide a new reference index for the clinical differentiation and disease evaluation of NMOSD and MS. Moreover, further studies are needed.

Background: Nutritional problems are common in children with cerebral palsy (CP), yet the relationship between nutritional status and the severity of CP is unclear.Objective: To describe the nutritional status and characteristics of children with CP, and to explore the relationship between severity of CP and nutritional status in children.Methods: This multicentre cross-sectional study included children with CP in China. Weight and height were measured and converted to z-scores. Gross Motor Function Classification System (GMFCS), Eating and Drinking Ability Classification System (EDACS), Subjective Global Nutritional Assessment (SGNA), social life ability, and blood indicators were tested.Results: All 1,151 participants were given oral-feeding and 50.8% of them demonstrated undernutrition. Compared with those in GMFCS or EDACS levels I–III, the odds of moderate and severe undernutrition were 2.6 and 8.9 times higher in GMFCS levels IV and V, and 4.3 and 12.6 times higher in EDACS levels IV and V, respectively. Except for serum 25-hydroxyvitamin D, no significant differenceswere found in blood indicators among normal, undernourished and overnourished groups.Conclusion: Degrees of undernutrition in children with CP are correlated with the severity of eating and drinking dysfunction and with gross motor impairment. Blood indicators may not reflect nutritional status in children with CP. LAY ABSTRACTCerebral palsy is the most common physical disability in children in the world. Children with cerebral palsy may have a high risk of having malnutrition as a result of the high energy consumption and/or low energy intake. The former is mainly caused by the abnormal muscular tone, and the latter may emerge from the dysphagia and gastrointestinal problems. As for the optimization of nutritional status is integral to the overall health and clinical management of children with cerebral palsy, the nutritional status stands out for its clinical importance in this group. Children with cerebral palsy are affected by different degrees of motor dysfunction, and may also be faced with eating and drinking problems or limited daily life ability, it is not clear whether nutritional status and function are interrelated. What's more, it is believed that the blood tests may indicate the nutritional status, but it is not well understood. In this project we will look at the nutritional status of children with cerebral palsy in China and investigate the relationship between nutritional status and function and blood indicators. This will then allow clinicians and caregivers to formulate future policies to improve nutritional status for this group of children.

Purpose To investigate the longitudinal changes in myopia from onset to stabilization in school-aged children with single-vison lenses (SVLs). Methods The medical records of patients wearing SVLs with long-term follow-up data between 2006 and 2016 were retrospectively reviewed. The patients who were 6-10 years old at the initial visit and 16 years old at the last assessment were included and analysed. The periods of progression and stabilization of myopia were evaluated by plotting fitted curves of the changes in spherical equivalent (SE). Results Seven hundred and seventy-three patients (median initial age 9 years) were accessed over an average of 7 years (IQR, 6-7 years). The initial mean SE was -1.92 ± 1.57 D and increased to -6.05 ± 2.14 D at 16 years old. The average age at myopia stabilization was 14.6 years, and girls slightly stabilized earlier than boys. 73.7% of the 6-year-olds and 85.7% of the 7-year-olds had high myopia at 16 years old, and the risk decreased each year from 7 to 10 years old. Children who had SE greater than -4 D up to 10 years had 89.0% risk of high myopia at 16 years old. Children with SE between -0.5 D and -2 D still had 34% risk of developing high myopia at 16 years old. Conclusion This study provides a comprehensive picture of myopia progression from onset to stabilization in school-aged children with SVLs in China. All children who have myopia onset below 10 years of age were at risk for high myopia, and children who have myopia onset below 8 years of age require more attention.

Osteoarthritis (OA) is a chronic joint disease with occurrence of articular inflammation and cartilage degeneration. An ideal drug delivery system for effective treatment of OA should integrate inflammation alleviation with cartilage protection. Herein, a lyotropic liquid crystal (LLC) precursor co-loading hyaluronic acid (HA) and celecoxib, formulated as the HLC precursor, was developed for the combined therapeutic efficacy. The

Huperzine A loaded multiparticulate tablet with sustained release was developed to reduce dosing frequency and increase swallowing. The sustained release was provided by the ethyl cellulose/Poloxamer 127 (EC/F127) microparticles (MPs). F127 was added to facilitate drug release of EC MPs, and the enhanced dissolution mechanism was investigated regarding to the particle size, water uptake, and wettability of MPs. The greater wettability, which highly relied on the medium and formulation components, generated larger water uptake and faster drug release through improving the penetration of the medium into the internal space of MPs. The EC/F127 MPs were further compressed into tablets for dissolution and pharmacokinetic studies. The results demonstrated that the tablet remained unchanged release profile to the MPs, and exhibited profoundly sustained release with a relatively bioavailability of 125.18% to the commercial tablet. Therefore, the multiparticulate tablet was successfully designed based on the drug release mechanism and high compressibility of MPs.

A hypertrophic scar (HS) is a cutaneous condition characterized by deposits of excessive amounts of collagen that produces a raised scar, causing physical, psychological, and cosmetic problems for the patient. The therapeutic efficacy of conventional transdermal drug delivery systems is often limited because the HS tissue is more compact than normal skin. At present, intralesional multi-injection of triamcinolone acetonide (TA) using a syringe is one of the most commonly used treatments for HS. However, the efficacy of this treatment is highly dependent on the skill of the medical professionals administering the injection. Even with co-administration of local anesthetics, traditional injection still causes pain to the patients, resulting in poor compliance. The purpose of this study was to provide an alternative treatment for HS by establishing a novel intradermal delivery system with a dissolving microneedle array (DMNA). To produce needles of higher mechanical strength for successful insertion into the compact and hard HS tissue, hydroxypropyl-β-cyclodextrin (HP-β-CD) was added into sodium hyaluronic acid (HA), the needle material. The hydrogen interaction between HP-β-CD and HA restricted the mobility of the molecular chains, and subsequently increased the elastic modulus of the complex materials. The HP-β-CD also contributed to improved loading of the hydrophobic drug molecules into the DMNA needle tips. To assess the delivery of TA to the HS site via DMNA, an HS model was established in the ventral skin of New Zealand rabbits' ears. It was found that the value of the scar elevation index was decreased to normal, together with the down regulation of mRNA expressions of Collagen I and transforming growth factor-β1 (TGF-β1) following the administration of DMNA containing TA (TA-DMNA). Western blotting results also revealed decreased protein expressions of both Collagen I and TGF-β1. Hence, TA-DMNA appears to be a promising alternative to multi-injection of TA injection, providing a convenient and low-pain therapeutic strategy for HS treatment.

Glaucoma is a chronic eye disease that causes loss of vision and it is irreversible. Accurate segmentation of optic disc and optic cup is a basic step in screening glaucoma. The most existing deep convolutional neural network (DCNN) methods have insufficient feature information extraction, and hence they are susceptible to pathological regions and low-quality images, with have poor ability to restore context information. Finally, the accuracy of the model segmentation is low. In this paper, we propose GL-Net, a multi-label DCNN model that combines the generative adversarial networks. GL-Net consists of two network structures including a Generator and a Discriminator. In the Generator, we use skip connection to promote the fusion of low-level feature information and high-level feature information, which alleviates the difficulty of restoring detailed feature information during upsampling, and reduces the downsampling factor, effectively alleviating excessive feature information loss. In the loss function, we add the $L_{1}$ distance function and the cross-entropy function to prevent the mode collapse when the model is trained, which makes the segmentation result more accurate. We use transfer learning and data augmentation to alleviate the problem of insufficient data and over-fitting of the model during training. Finally, GL-Net was verified on DRISHTI-GS1 dataset. The experimental results show that GL-Net outperforms some state-of-the-art method, such as M-Net, Stack-U-Net, RACE-net, and BCRF in terms of $F1$ and boundary distance localization error (BLE). Particularly, in the optic cup segmentation, GL-Net outperforms RACE-net by 3.5% and 4.16 pixels in terms of $F1$ and BLE, respectively.

Accurate segmentation of retinal vessels is a basic step in diabetic retinopathy (DR) detection. Most methods based on deep convolutional neural network (DCNN) have small receptive fields, and hence they are unable to capture global context information of larger regions, with difficult to identify pathological. The final segmented retina vessels contain more noise with low classification accuracy. Therefore, in this paper, we propose a DCNN structure named as D-Net. In the encoding phase, we reduced the loss of feature information by reducing the downsampling factor, which reduced the difficulty of tiny thin vessels segmentation. We use the combined dilated convolution to effectively enlarge the receptive field of the network and alleviate the “grid problem” that exists in the standard dilated convolution. In the proposed multi-scale information fusion module (MSIF), parallel convolution layers with different dilation rates are used, so that the model can obtain more dense feature information and better capture retinal vessel information of different sizes. In the decoding module, the skip layer connection is used to propagate context information to higher resolution layers, so as to prevent low-level information from passing the entire network structure. Finally, our method was verified on DRIVE, STARE, and CHASE dataset. The experimental results show that our network structure outperforms some state-of-art method, such as N4-fields, U-Net, and DRIU in terms of accuracy, sensitivity, specificity, and ${AUC_{ROC}}$ . Particularly, D-Net outperforms U-Net by 1.04 %, 1.23 %, and 2.79% in DRIVE, STARE, and CHASE dataset, respectively.

There is a great challenge in regenerating cartilage defects, which usually involve absent bearing capacity and poor adaptation to joint movement, further exacerbating subchondral bone damage. Therefore, ideal tissue-engineering cartilage scaffolds should be endowed with biomimetic and sustained-release function for promoting long-term chondrogenesis while protecting subchondral bone. Herein, in situ self-assembling gel based on glyceryl monooleate (GMO)-hyaluronic acid (HA) composite lyotropic liquid crystal (HLC) was developed as the biomimetic scaffold to deliver kartogenin for long-term cartilage regeneration. Compared to the GMO based (LLC) gel, HLC gel with modified lattice structure exhibited improved rheological properties for better joint protection by increasing mechanical strength, elasticity and lubrication. Besides, HLC gel successfully prolonged drug release and retention in the joint cavity over 4 weeks to provide combined effect of kartogenin and HA for cartilage repair. Pharmacodynamic studies demonstrated that HLC gel was the most effective to promote chondrogenesis and protect subchondral bone, making the damaged bone tissue restored to normal in divergent features as evidenced by the MRI, Micro-CT and histological results. Therefore, the HLC gel with joint protection and controlled drug release can serve as a firm scaffold for providing long-term cartilage repair.

PurposeTo study the longitudinal rehabilitation of binocular visual function in adolescent intermittent exotropia (IXT) after successful surgery and compare the results with those of a normal population. The role of binocular function in ocular alignment stability was also evaluated postoperatively.MethodsIn this prospective study, 30 adolescents with IXT successfully corrected after 1 month were followed for 12 months, and 30 children with normal vision were enrolled as controls. Stereopsis, the fusional vergence amplitude, sensory fusion, and accommodative flexibility were measured to assess binocular function at baseline and 6 and 12 months postoperatively. The controls were tested once when they were enrolled in the study.ResultsThe deviation was −32.00 ± 8.60 prism diopters (PD) at distance fixation and −36.0 ± 9.10 PD at near fixation preoperatively with an average correction of 28.53 ± 3.79 PD and 30.67 ± 1.34 PD at 1 month postoperatively. Distance stereoacuity and near stereoacuity improved from 1 to 12 months postoperatively (p = 0.025 and p = 0.041, respectively). Compared with the controls, the fusional convergence reserve at distance (p = 0.025) and near (p = 0.033) fixations and fusion reserve ratio at distance (p = 0.000) and near (p = 0.000) fixations remained subnormal, whereas sensory fusion (p = 0.237), distance stereopsis (p = 0.120), and the fusional divergence amplitude at a distance (p = 0.168) were normal. However, no significant correlations were found between binocular functions at 1 month postoperatively and the postoperative drift.ConclusionBinocular function significantly improved from before to after successful corrective surgery and continued to improve from 1 to 12 months postoperatively in adolescents with IXT. No significant correlations were found between binocular functions at 1 month postoperatively and ocular alignment stability.

Lanthanide-doped upconversion nanoparticles (UCNPs) are promising bioimaging nanoprobes due to their excellent photostability. As one of the most commonly used lanthanide activators, Tm3+ ions have perfect ladder-type electron configuration and can be directly excited by bio-friendly near-infrared-II (NIR-II) wavelengths. Here, the emission characteristics of Tm3+-doped nanoparticles under laser excitations of different near-infrared-II wavelengths were systematically investigated. The 1064 nm, 1150 nm, and 1208 nm lasers are proposed to be three excitation strategies with different response spectra of Tm3+ ions. In particular, we found that 1150 nm laser excitation enables intense three-photon 475 nm emission, which is nearly 100 times stronger than that excited by 1064 nm excitation. We further optimized the luminescence brightness after investigating the luminescence quenching mechanism of bare NaYF4: Tm (1.75%) core. After growing an inert shell, a ten-fold increase of emission intensity was achieved. Combining the advantages of NIR-II wavelength and the higher-order nonlinear excitation, a promising facile excitation strategy was developed for the application of thulium-doped upconversion nanoparticles in nanoparticles imaging and cancer cell microscopic imaging.

A total of two red oleaginous yeasts, Rhodotorula diobovata and Rhodosporidium babjevae, were investigated for their potential to grow on nitrogen-limited media with sufficient glycerol as carbon source and produce biomass, triacylglycerides (TAGs) and carotenoids. The two yeasts produced equal quantities of biomass by 120 h post-inoculation (h pi), but R. diobovata consumed more glycerol than R. babajavae under the same conditions. The TAG concentrations accumulated by R. diobovata and R. babjevae were greater than 20% dry cell weight (dcw), and the major fatty acid components consisted of palmitic acid, oleic acid and linolenic acid. The highest concentration of total fatty acids in biomass were present during the late of stationary phase were 486.3 mg/g dcw for R. diobovata at 120 h pi, and 243.9 mg/g dcw for R. babjevae at 144 h pi. Both R. diobovata and R. babjevae produced high concentrations of torularhodin, and low amounts of torulene and γ-carotene. Total carotenoid concentrations in R. diobovata biomass were 31.5 mg/g dcw at 120 h pi and 43.1 mg/g dcw at 96 h pi for R. babjevae. The dcw accumulations of carotenoids by R. diobovata and R. babjevae were significantly greater than those reported for other carotenogenic Rhodotorula and Rhodosporidium strains.

To effectively utilize a feature set to further improve fault diagnosis of a rolling bearing vibration signal, a method based on multi-fractal detrended fluctuation analysis (MF-DFA) and smooth intrinsic time-scale decomposition (SITD) was proposed. The vibration signal was decomposed into several proper rotation components by applying this new SITD method to overcome noise effects, preserve the effective signal, and improve the signal-to-noise ratio. Wavelet analysis was embedded in iteration procedures of intrinsic time-scale decomposition (ITD). For better results, an adaptive threshold function was used for signal recovery from noisy proper rotation components in the wavelet domain. Additionally, MF-DFA was used to reveal the multi-fractality present in the instantaneous amplitude of the proper rotation components. Finally, linear local tangent space alignment was applied for feature dimension reduction and to obtain fault characteristics of different types, further improving identification accuracy. The performance of the proposed method is determined to be superior to that of the ITD-MF-DFA method.

Photodynamic therapy (PDT), a clinically approved cancer treatment strategy, features non-invasiveness, few side-effects, high spatial resolution, etc. The advancement of PDT has been significantly restricted by the penetration depth of the excitation light. Herein, an effective fluorogen, TBD, with aggregation-induced emission characteristics (AIEgen) and high reactive-oxygen-species (ROS) generation efficiency was reported and integrated with a near infrared (NIR) light excitable upconversion nanoparticle (UCNP) to construct NIR light excitable UCNP@TBD nanocomposites. The formed nanocomposite has excellent photostability, good biocompatibility, and efficient ROS generation under NIR light excitation via Forster resonance energy transfer (FRET), enabling NIR light excited PDT. Moreover, the proposed NIR light excited PDT can break the impasse between the penetration depth and excitation volume in conventional PDT, effectively improving the anticancer therapeutic outcome. In vitro cancer cell ablation and in vivo tumor growth inhibition validated that the proposed UCNP@TBD nanocomposite is a promising NIR light excitable PDT agent with great potential for future translational research.

The ultra-fine particle processing system (UPPS) previously developed by our lab has been used to prepare various microparticulate formulations. Microspheres prepared by UPPS can achieve sustained release with a reduced initial burst compared to the microspheres prepared by the conventional water-in-oil-in-water (W/O/W) double emulsion technique. However, the in vitro drug release mechanism of the microspheres prepared by UPPS is still uninvestigated. This study aimed to investigate the mechanisms of bovine serum albumin (BSA) released from poly (D,L-lactic-co-glycolic acid) (PLGA) microspheres prepared by UPPS in comparison with microspheres prepared by the W/O/W double emulsion technique. The morphology, in vitro drug release, water uptake, and structural evolution of microspheres prepared by both techniques were evaluated. UPPS microspheres showed solid and compact internal structures without any pores or channels thereby exhibiting a reduced rate of water permeation in the release medium. In addition, the release of BSA in UPPS microspheres was mainly controlled by the erosion of the polymer matrix during the entire process, while BSA was released from W/O/W microspheres by both drug diffusion and matrix erosion. Moreover, the observed surface and internal structural evolution also confirmed their different release mechanisms. This work elaborates the release mechanism of PLGA microspheres prepared by UPPS and facilitates the design of microparticulate formulations. Graphical abstract.

Introduction: DBS is a widely used therapy for PD. There is now a choice between fixed-life implantable pulse generators (IPGs) and rechargeable IPGs, each having advantages and disadvantages. This study aimed to evaluate the preference and satisfaction of Chinese patients with Parkinson's disease (PD) who were treated with deep brain stimulation (DBS).Materials and Methods: Two hundred and twenty PD patients were treated with DBS and completed a self-reported questionnaire to assess their long-term satisfaction and experience with the type of battery they had chosen and the key factors affecting these choices. The survey was performed online and double-checked for completeness and accuracy.Results: The median value of the postoperative duration was 18 months. The most popular way for patients to learn about DBS surgery was through media (79/220, 35.9%) including the Internet and television programs. In total, 87.3% of the DBS used rechargeable IPGs (r-IPG). The choice between rechargeable and non-rechargeable IPGs was significantly associated with affordability (χ(1)2 = 19.13, p < 0.001). Interestingly, the feature of remote programming significantly affected patients' choices between domestic and imported brands (χ(1)2 = 16.81, p < 0.001). 87.7% of the patients were satisfied with the stimulating effects as well as the implanted device itself. 40.6% of the patients with r-IPGs felt confident handling devices within 1 week after discharge. More than half of the patients checked their batteries every week. The mean interval for battery recharge was 4.3 days. 57.8% of the patients spent around 1 h recharging, and 71.4% of them recharged the battery independently.Conclusions: Most patients were satisfied with their choice of IPGs. The patients' economic status and the remote programming function of the device were the two most critical factors in their decision. The skill of recharging the IPG was easy to master for most patients.

Emulsions containing unsaturated fatty acids (UFAs) have potential in the treatment of clinical malnutrition. However, the stability of UFAs is a major problem due to the presence of double bonds, which are susceptible to oxidation, leading to the loss of nutrition and even resulting in side effects. The factors that affect the UFAs are complex, and the protective effect of single antioxidant is not satisfactory. The goal of the study was the development of UFA-enriched oil-in-water (O/W) emulsions with improved stability, simultaneously employing a hydrophilic (catechol) and a hydrophobic (tocopherol) antioxidant, and then to investigate the stabilization mechanisms of catechol and tocopherol for emulsions. The emulsions obtained in this study showed uniform nanoscale droplets and good storage stability for three months under accelerated conditions. More than 93.0% of fatty acids remained unchanged after six months of storage, which demonstrated the protective effects of catechol and tocopherol. The dual antioxidant emulsions were remarkably effective in protecting the UFAs compared to emulsions with a single antioxidant or without any antioxidant. This dual antioxidant emulsion system provides new opportunities for the transmission of oxidation-prone nutrients, and its prospects are optimistic.

Amorphous solid dispersions (ASDs) are inherently unstable because of high internal energy. Evaluating physical and chemical stability during the process and storage is essential. Numerous researches have demonstrated how polymers influence the drug precipitation and physical stability of ASDs, while the influence of polymers on the chemical stability of ASDs is often overlooked. Therefore, this study aimed to investigate the effect of polymers on the physical and chemical stability of spray-dried ASDs using dipyridamole (DP) as a model drug. Proper polymers were selected by assessing their abilities to inhibit drug recrystallization in supersaturated solutions. HPMC E5, Soluplus®, HPMCP-55, and HPMCAS-LP were shown to be effective stabilizers. The optimized formulations were further stored at a high temperature (60 °C) and high humidity (40 °C, 75% RH) for 2 months, and their physical and chemical stability was evaluated using polarizing optical microscopy, FTIR, HPLC, and mass spectrometry (MS). In general, crystallization was observed in all samples, which indicated the physical instability under stressed storage conditions. Also, it was noted that the polymers in ASDs rather than physical mixtures, induced a dramatic drug degradation after being exposed to a high temperature (HPMCP-55 > 80% and HPMCAS-LP > 50%) and high humidity (HPMCP-55 > 40% and HPMCAS-LP > 10%). The MS analysis further confirmed the degradation products, which might be generated from the reaction between dipyridamole and phthalic anhydride decomposed from HPMCP-55 and HPMCAS-LP. Overall, the exposure of ASDs to stressed conditions resulted in recrystallization and even the chemical degradation induced by polymers.

Background Daytime napping has been postulated as both a protective and a risk factor for depression in previous studies. In addition to these conflicting results, research gaps also exist with regard to controlling confounding bias between daytime napping and depression and examining the potential association within the Chinese population. To facilitate the prevention and diagnosis of depression, this study aims to provide insight into the association of daytime napping and depression in 0.5 million Chinese adults by fully controlling confounders, and further examine the modifying effects of socio-economic status (SES) and age. Methods Data were drawn from the baseline of a Chinese cohort study of 0.5 million adults. Depressive status was measured by the Composite International Diagnostic Inventory (CIDI). Logistic regression models were used to examine the association between depression and daytime napping adjusted for SES, sleep-related factors, lifestyle factors and related diseases. Further stratified analyses were conducted to identify the modifying effects of socio-economic status and age. Results The odds ratio of depression by daytime napping was 1.15 (95% CI: 1.01–1.31) in females and 1.42 (95% CI: 1.18–1.71) in males. Factors including living in a rural area (OR = 1.31, 95% CI: 1.13–1.52), receiving less education (OR = 1.42, 95% CI: 1.22–1.66), getting married (OR = 1.24, 95% CI: 1.10–1.40) and being 45–65 years old (OR = 1.29, 95% CI: 1.12–1.49) had a modifying effect on daytime napping and depression that could strengthen the association. Conclusions A significantly positive association was found between depression and daytime napping, as well as daytime dysfunction, snoring and both shorter and longer sleep duration. Lower SES and age could possibly modify the association. Further clinical or epidemiological studies are needed to investigate the mechanism and facilitate the prevention of depression.

Carbon fiber reinforced polymer has been used as a major material for primary load-bearing structural components in aviation industry. But its poor heat resistance is an important factor affecting the machining performance, because high cutting temperature above glass transition temperature of resin matrix (normally 300°C or below) may lead to the degradation of the resin matrix. In this study, orthogonal machining experiments were conducted to investigate the effects of cutting parameters, cutting tool geometric parameters, and material parameters on cutting temperature, and the prediction model of cutting temperature about fiber orientation angle ( θ) was built. Cutting temperature was measured by semiartificial thermocouple method. The experimental results revealed that the influence of cutting parameters on cutting temperature was not affected by fiber orientation angle of carbon fiber reinforced polymer. Cutting tool geometric parameters have little effect on cutting temperature. Unlike metal materials, cutting temperature was greatly influenced by θ. Cutting temperature for θ 90°. The maximum temperature occurred at θ = 90°. The influence of fiber orientation angle was shown in two aspects: changing the springback of unidirectional-carbon fiber reinforced polymer laminates in cutting process, changing material removal mechanism, which affected cutting temperature eventually.

A set of five metal–organic frameworks, namely, [Cd 2 (L) 2 BIP(H 2 O) 2 ·6H 2 O] n (1) , [Ce(L) 1.5 (H 2 O) 2 ·H 2 O] n (2) , [Sm(L) 1.5 (H 2 O) 2 ·3H 2 O] n (3) , [Gd(L) 1.5 (H 2 O) 2 ·3H 2 O] n (4) , [Ho(L) 1.5 (H 2 O) 2 ·3H 2 O] n (5) , have been prepared under hydrothermal conditions (1,4-H 2 L = 1,4-Pheny lenedioxydiacetic acid; 1,4-BIP = 1,4-bis(2-pyridylmethyl)piperazi-ne; C2H5OH = EtOH). The long BIP ligand (N ⋯ N separation of ca. 8.355 A) induces interpenetration of 1 to increase both the framework stability and the density of effective catalytic metal centers. Characterization of all complexes has been carried out by means of IR spectroscopy, single crystal and powdered sample X-ray diffraction (PXRD) through conventional and synchrotron radiation, Thermogravimetric (TG), fluorescent measurement (liquid and solid), DNA molecular docking, cancer cell apoptosis morphology through fluorescent inverted microscope, IC 50 , which the cytotoxic activity of the complexes was tested against two different cancer and one normal cell lines. The results indicate that all the complexes are potential fluorescent light-emitting materials and the flour ( 2 , 3 , 4 , 5 ) complexes present remarkable anti-cancer effect.