Background: Prosthetic valve endocarditis (PVE) is a rare but dangerous complication after Bentall surgery. In addition, cases of Staphylococcus epidermidis involving multiple valves simultaneously and multi-organ embolism during the early postoperative period are rarer. Case presentation: We reported a 42-year-old patient who developed PVE with systemic embolism one month after aortic valve replacement (Bentall surgery). Echocardiography suggested large, mobile vegetations on both the prosthetic aortic valve and native tricuspid valve. The patient immediately received antibiotic treatment after the presence of Staphylococcus epidermidis was revealed by multiple blood cultures. Shortly after that, the patient felt numbness in the right lower extremity and received a vascular ultrasonography examination. The Pathological exam revealed right femoral artery thromboembolism. The patient also developed cerebral and splenic infarction during follow-ups and died of cerebral infarction. Conclusions: We reported a sporadic case of Staphylococcus epidermidis infective endocarditis (IE) involving multiple valves and systemic embolisms early after Bentall surgery in a patient with Marfan’s syndrome. Fatal systemic embolism should be aware of in PVE patients with large vegetations present with dyskinesia, abdominal pain, and limb numbness. The prompt echocardiography and vascular ultrasound are primary and reliable diagnostic methods in this scenario.

In this paper, we propose a new structure-preserving algorithm for computing the singular value decomposition of a quaternion matrix $A$. We first define a quaternion-type matrix and prove that the multiplication of two quaternion-type matrices still be a quaternion-type matrix. Thus, utilizing this fact, we conduct a sequence of quaternion-type unitary transformations on a half of the elements of the complex adjoint matrix $\chi_A$ of $A$ instead of on the whole $\chi_A$. Then, we recover the resulting matrix with the help of the special structures. Compared with direct performing on the complex adjoint matrix, our algorithm needs only half of the computation and storage. This method also provides a novel proof for the existence of the singular value decomposition of a quaternion matrix. Moreover, numerical experiments are given to demonstrate the validity of our approach.

We are concerned with a Dirichlet system, involving the Monge-Ampere operator \det D^2u in a ball in \mathbb{R}^N. Based on the Leray-Schauder degree, we first obtain the existence of radial solutions for a class of differential systems with general nonlinearities. In addition, we prove that such a system admits positive solutions when nonlinearities satisfy sub- or superlinear growth near origin. Finally, by using the lower and upper solution method, and constructing the subsolution and supersolution, we show the existence and multiplicity of nontrivial radial solutions for Dirichlet systems with Monge-Ampere operator and Lane-Emden type nonlinearities with two parameters.

Objective To assess the perception, knowledge, and practices regarding maternal perception of fetal movements (FMs) among women and their healthcare providers in a low-resource setting. Design Qualitative study. Setting The maternity unit of Mnazi Mmoja Hospital, Zanzibar, Tanzania. Population Pregnant and postpartum women, and health providers. Methods Semi-structured interviews, questionnaires and focus group discussions were conducted with 45 Zanzibar women (18 antenatal, 28 postpartum) and 28 health providers. Main outcome measures Descriptive and thematic analyses were conducted to systematically extract subthemes within four main themes 1) knowledge/awareness, 2) behavior/practice, 3) barriers, and 4) improvements. Results Within the main themes it was found that 1) Women were instinctively aware of (ab)normal FM-patterns and healthcare providers had adequate knowledge about FMs. 2) Women often did not know how to monitor FMs or when to report concerns. There was inadequate assessment and management of (ab)normal FMs. 3) Women did not feel free to express concerns. Healthcare providers considered FM-awareness among women as low and unreliable; lack of staff, time and space for FM-education, and no protocol for FM-management. 4) Women and health providers recognized the need for education on assessment and management of (ab)normal FMs. Conclusion Women expressed FMs in an adequate way and perceived abnormalities of these movements better than assumed by health providers. There is a need for more evidence on the effect of improving knowledge and awareness of FMs in order to construct evidence-based guidelines for low resource settings.

Objective: To describe clinical and laboratory characteristics of term deliveries complicated by chorioamnionitis, and to assess their association with adverse neonatal outcomes. Design: Cross-sectional cohort study Setting: The study is based on data from the Swedish Pregnancy Register, enriched with clinical data extracted from medical charts. Population and Sample: A random sample of 500 term singleton deliveries in Stockholm County with registered diagnosis of chorioamnionitis in the Swedish Pregnancy Register between 2014 and 2020. Methods: Logistic regression was used to estimate odds ratios (OR) as a measurement of the association between clinical and laboratory characteristics and neonatal complications Main Outcome Measures: Neonatal infection and asphyxia-related complications. Results: Maternal fever, maternal and fetal tachycardia, and elevated inflammatory laboratory markers were frequent signs of chorioamnionitis. The prevalence of neonatal infection and asphyxia-related complications was 10 and 22%, respectively. First leukocyte count in the second tertile (OR 2.14 [95% CI 1.02-4.49]), maximum CRP level in the third tertile (OR 4.01 [95% Cl 1.66-9.68]), and positive cervical culture (OR 2.22 [95% Cl 1.10-4.48]) were associated with an increased risk of neonatal infection. Maximum level of CRP in the third tertile (OR 1.93 [95% Cl 1.09-3.41]), and fetal tachycardia (OR 1.63 [95% Cl 1.01-2.65]) were associated with increased risk of asphyxia-related complications. Conclusions: In addition to maternal intrapartum fever, maternal and fetal tachycardia, and elevated inflammatory laboratory markers were common signs of chorioamnionitis. Elevated inflammatory laboratory markers were associated with both neonatal infection and asphyxia-related complications, and fetal tachycardia was associated asphyxia-related complications.

Objective This study compares survival of four different surgical approaches including ARH, LRH, RRH and VRH for early-stage cervical cancer in order to define the best effects and survivals for patients. Design Retrospective study. Setting The First Medical Center of the PLA General Hospital. Population 238 women diagnosed early-stage cervical cancer between January 2013 and December 2017 and followed up until September 2020. Methods All patients with early-stage cervical cancer were retrospective collected in the first medical center of the PLA general hospital. Disease free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier’s method, and survival curves were compared using log-rank test. Main outcome measures Outcomes were the comparison of patients’ DFS and OS between the four different radical hysterectomy approaches. Results The intraoperative blood loss and postoperative exhaust time of LRH, RRH and VRH groups are better than that in ARH group. The total 5-year OS was significant difference among the four groups. However, the difference of 5-year DFS was not statistically significant among the four groups. Furthermore, patients with early-stage cervical cancer had a significantly better DFS and OS in ARH and RRH groups than that in LRH and VRH groups. Conclusions This retrospective study demonstrated that both ARH and RRH obtained higher rate of 5-year DFS and 5-year OS compared with LRH and VRH for early-stage cervical cancer, and the survival outcomes between ARH and RRH were similar. Keywords Cervical cancer, ARH, LRH, RRH, VRH, survival.

Variants of Severe-Acute-Respiratory-Syndrome Coronavirus-2 (SARS-CoV-2) has caused tremendous impact globally. It has been widely reported that the Omicron (B.1.1.529) variant is less deadly than the Delta (B.1.617.2) variant, presumably due to immunity from vaccination and previous infection. When measuring the severity of a variant, Case-Fatality-Rate (CFR) is often estimated. The purpose of this work is to calculate the change in CFR of different variants over time from a large number of countries/regions since the start of the pandemic in 2020.

An individual’s fitness cost associated with environmental change depends on the rate of adaptive phenotypic plasticity, and yet our understanding of plasticity rates in an ecological and evolutionary context remains limited. We provide the first quantitative synthesis of existing plasticity rate data, focusing on acclimation of temperature tolerance in ectothermic animals, where we demonstrate applicability of a recently proposed analytical approach. The analyses reveal considerable variation in plasticity rates of this trait among species, with half-times (how long it takes for the initial deviation from the acclimated phenotype to be reduced by 50% when individuals are shifted to a new environment) ranging from 3.7 to 770.2 h. Furthermore, rates differ among higher taxa, being higher for amphibians and reptiles than for crustaceans and fishes, and with insects being intermediate. We argue that a more comprehensive understanding of phenotypic plasticity will be attained through increased focus on the rate parameter.

Objectives: To compare outcomes of telephone and face-to-face consultations for new otology referrals and discuss the wider use of telemedicine in otology. Design: Retrospective cohort study. Setting: UK secondary/tertiary referral unit. Participants: New adult otology referrals to our unit, sampled consecutively between March 2021 and May 2021, reviewed in either a face-to-face or telephone clinic. Main outcome measures: Primary outcome measure was the proportion of patients with a definitive management outcome (discharged or added to waiting list for treatment) versus the proportion of patients requiring follow-up for further assessment or review. Results: 150 new patients referred for a routine otology consultation (75 telephone, 75 face-to-face) were included. 53/75 patients (71%) undergoing a face-to-face consultation received a definitive outcome following initial review, versus 22/75 (29%) telephone patients (2 <0.001, OR 5.8). 52/75 (69%) telephone patients were followed up face-to-face for examination. The mean (SD) number of appointments required to reach a definitive outcome was 1.22 (0.58) and 1.75 (0.73) in the face-to-face and telephone cohorts respectively (p<0.001). Conclusion: Telephone clinics in otology have played an important role as part of the COVID19 response. However, they are currently limited by a lack of clinical examination and audiometry. Remote assessment pathways in otology that incorporate asynchronous review of recorded examinations alongside audiometry, either conventional or boothless, may mitigate this problem, however further research is required.

Objectives: The purpose of this study was to compare the incidences of common upper airway infections and their complications, and of antibiotic prescription rates during 2020, when the COVID-19 pandemic struck, and the previous year. Study design: Retrospective national register study Setting/source population: The Swedish population in 2019 and 2020. Methods: The Swedish Board of Health and Welfare statistics data base, which includes all out- and inpatient diagnoses in specialised care was used to retrieve the number of otitis media, rhinosinusitis, pharyngotonsillitis, acute mastoiditis and peritonsillar abscess diagnoses in various age groups during 2019 and 2020. The number of prescriptions of oral antibiotics used to treat upper airway infections was collected from the Swedish E-Health Authority, which covers all prescriptions in Sweden. Population data were retrieved from Statistics Sweden. Results: There was strong evidence of a substantial decrease (approximately 40%) in otitis media, rhinosinusitis and pharyngotonsillitis cases in the population as a whole in 2020 compared to 2019. For otitis media, the decrease was most pronounced among children, whereas rhinosinusitis and pharyngotonsillitis incidence decreased to a similar extent in adults, as well. Furthermore, there was equally strong evidence that acute mastoiditis decreased by 40% in children and adolescents and that peritonsillitis in adults decreased by 24%. The decrease in infections was accompanied by a corresponding decrease in antibiotic prescriptions. Conclusion: The social distancing measures introduced during 2020 were followed by a significant decrease in upper airway infections and antibiotic prescriptions.

Species turnover is fundamental for understanding the mechanisms that influence large-scale species richness patterns. However, the large-scale spatial variation and the causes in soil animal species turnover remain elusive. In addition, the determinants of species turnover depend on the dispersal ability of guilds. In this study, we explored the large-scale patterns of meso-micro soil fauna turnover pattern and the driving factors based on fourteen sampling sites in East Asia. The patterns of soil fauna species turnover increased significantly with increasing latitude differences in East Asia. The environment explained 54.09, 50.62, and 57.34% of the total variance, and spatial factors explained 13.84, 15.91, and 21.04% of the total variance in species composition of overall, phytophage, and predacity faunas, respectively. Meanwhile, the effects of climate factors in environmental processes were stronger than that of soil factors in these three groups. Our results support the hypothesis that the effect of environment processes on soil animal species turnover is more important than the effect of the neutral. Climatic factors explained more variation for turnover of phytophage faunas, but soil and environment factors explained equally for predacity. Our results provide evidence supporting both environmental filtering and dispersal limitation hypotheses on the reginal and population scales. At last, this study has important theoretical significance and applied value in maintaining and promoting soil biodiversity and ecosystem services on the large scale.

The usual features of the acrocallosal syndrome (ACLS) are agenesis of the corpus callosum, mental retardation, prominent craniofacial deformities, and specific digital abnormalities. We discuss the case of a neonate with ACLS-consistent characteristics. The occurrence of this syndrome may have been caused by maternal exposure to cosmetics-related substances during pregnancy.

Characteristic of Sound Localisation of Unilateral Microtia and Atresia with and without a Non-surgical Bone Conduction Device

The accurate delimitation of species boundaries in non-bilaterian marine taxa is notoriously difficult, with consequences for many studies in ecology and evolution. Anthozoans are a diverse group of key structural organisms worldwide, but the lack of reliable morphological characters and informative genetic markers hampers our ability to understand species diversification. We investigated population differentiation and species limits in Atlantic (Iberian Peninsula) and Mediterranean lineages of the octocoral genus Paramuricea previously identified as P. clavata. We used a diverse set of molecular markers (microsatellites, RNA-seq derived single-copy orthologues [SCO] and mt-mutS [mitochondria]) at 49 locations. Clear segregation of Atlantic and Mediterranean lineages was found with all markers. Species-tree estimations based on SCO strongly supported these two clades as distinct, recently diverged sister species with incomplete lineage sorting, P. cf. grayi and P. clavata, respectively. Furthermore, a second putative (or ongoing) speciation event was detected in the Atlantic between two P. cf. grayi colour morphotypes (yellow and purple) using SCO and supported by microsatellites. While segregating P. cf. grayi lineages showed considerable geographic structure, dominating circalittoral communities in southern (yellow) and western (purple) Portugal, their occurrence in sympatry at some localities suggests a degree of reproductive isolation. Overall, our results show that previous molecular and morphological studies have underestimated species diversity in Paramuricea occurring in the Iberian Peninsula, which has important implications for conservation planning. Finally, our findings validate the usefulness of phylotranscriptomics for resolving evolutionary relationships in octocorals.

Doxorubicin (DOX) is a highly useful antineoplastic in the treatment of different types of cancer; however, its use is limited due to its wide variability between patients in their susceptibility to the cardiotoxic effects of anthracyclines. Purpose: The aim of this study was to determine the effect of single nucleotide variants (SNV) and the nutritional status on the population pharmacokinetics of DOX, and their repercussions on cardiotoxicity in pediatric patients with leukemia. Patients and methods: Seventy pediatric patients treated with DOX were studied, in whom 189 biological samples (1 to 3 samples per patient) were obtained at different random times, for 20 hours. Results: Body mass index, age ≤ 7 years and female sex were associated with a decrease in DOX clearance. Low height was associated with an increase in pharmacokinetics parameters of DOX. The Wild type (WT) genotype of ABCC1 rs3743527 variant was associated with an increase in clearance (CL), and the homozygous variant (HV) genotype of NCF4 rs1883112 SNV was associated with a decrease in peripheral compartment (V2) of the peripheral compartment. Conclusion: The SNV of the ABCC1 and NCF4 genes influence the increase and decrease in DOX CL, in addition, characteristics such as sex and height were associated with the decrease and increase in DOX CL respectively. The pharmacokinetic parameters show an influence on the development of cardiotoxicity by DOX. The decrease in CL and V2 were associated with systolic disfunction. The decrease in the intercompartmental clearance (Q) and in the volume distribution (V2) were associated with diastolic disfunction. In clinical practice, these results may contribute to the effective and safe use of DOX in pediatric cancer patients.

Pediatric GIST (gastrointestinal stromal tumors) are mostly KIT/ PDGFRA-WT and harbor mutations in SDH (succinate dehydrogenase), making them TKI (tyrosine kinase inhibitor) resistant due to the absence of gain-of-function tyrosine kinase mutations. Due to rarity of GIST in children, there have been few clinical trials available for patients with advanced disease, resulting in limited treatment options and a lack of pediatric-specific consensus guidelines. Here, we report the case of a patient with progressive, metastatic SDHB-mutant GIST that displayed a significant clinical response with a combination of Olaparib and TMZ (temozolomide).

The sulfur cycle is one of the geochemical element cycles in which microorganisms play a key driving role. The microbial function of soil S cycling in response to desert degradation, however, remains largely unknown. We used metagenomics to analyze the characteristics of microbial communities and their functional genes involved in the S cycles under natural water gradients with three typical halophytes shrubs in the Ebinur Lake Basin Desert, China. Our results showed that the rhizosphere effect, water gradient, and halophyte type played a major role in shaping the S cycle. On the whole, in the rhizosphere type and low water environment, the functional genes involved in the S cycle had high abundance, and the SOX system in Alhagi sparsifolia had a high expression level. In the S cycle network structure, as the soil water content decreased, the complexity in S gene networks increased, showing the characteristics of clustering and high connectivity. Indicates the strengthening mode in microbial interactions with the water content. Interestingly, the negative correlation of the network changed with the water content, and there was more competition among communities under the low water gradient and more cooperation under the high water gradient. Through the correlation between environmental factors and the network, nitrate (NO 3 −) and soil available S (AS) constrained most S gene ecology networks. The key species involved in the S cycle were halophilic microorganisms. These results can enhance the understanding of soil S biogeochemical processes and contribute to the mitigation of desertification by improving soil conservation.

Understanding how evolutionary pressures relating to climate changes have shaped the genetic background of present day domestic animals is a fundamental pursuit in biology. Here, we generated whole genome sequence data from native goat populations in Iraq and Pakistan countries. Together with published data from worldwide modern, historical remains and wild caprid species (including ibex like species, bezoar and markhor goats) we explore genetic population structure, ancestry components and signatures of natural positive selection of native goat populations in Southwest Asia (SWA) region. Our results revealed that the genetic structure of SWA goats was deeply influenced by the gene flow from eastern Mediterranean area during the Chalcolithic period, which may reflect the adaptation to the gradual warming and aridity in this region. Furthermore, a comparative genomic analysis revealed adaptive introgression of KITLG locus from the Nubian ibex (Capra nubiana) into African and SWA goats. The frequency of the selected allele at this locus was found significantly higher among the goat populations located close to the north-east of Africa. The Nubian ibex is a wild relative of the domestic goat that is well adapted to the arid mountains of north Africa and the Middle East. These results provide new insights into the genetic composition and history of goat populations in SWA region.

Rydberg-atom electrometers have the remarkable advantages of self-calibration and high sensitivity. Based on the classical electromagnetic theory, a localized electric field enhancement structure of a hybrid rectangular resonator is proposed to improve the sensitivity of quantum microwave measurement. It should be noted that the prototype of the hybrid rectangular resonator is fabricated and measured at 9.925 GHz. The results of full-wave simulations show that the uniform and high electric field enhancement in the TE101 fundamental mode is realized. The transient process of resonance is simultaneously simulated, and the time to settle steady state is given as about 104 ns. As indicated through experimental results that the structure can reach 24 dB (enhancement factor of 15.8). As a result, the method proposed in this study, based on atomic measurement capabilities, enables us to improve the measurement sensitivity further and promotes the practical development of quantum microwave measurement technology.

Affective video content analysis is an active topic in the field of affective computing. In general, affective video content can be depicted by feature vectors of multiple modalities, so it is important to effectively fuse information. In this work, a novel framework is designed to fuse information from multiple stages in a unified manner. In particular, a unified fusion layer is devised to combine output tensors from multiple stages of the proposed neural network. With the unified fusion layer, a bidirectional residual recurrent fusion block is devised to model the information of each modality. Moreover, the proposed method achieves state-of-the-art performances on two challenging datasets, i.e., the accuracy value on the VideoEmotion dataset is 55.8%, and the MSE values on the two domains of EIMT16 are 0.464 and 0.176 respectively. The code of UMFN is available at: https://github.com/yunyi9/UMFN.

Objective: This systematic review aimed to systematize different designs of exercise-based pulmonary rehabilitation (PR) for children with asthma and explore which designs are optimal. Methods: PubMed, EMBASE, Cochrane Library, Web of Science Core Collection and MEDLINE were searched up until April 01, 2021, which was conducted for any relevant randomized controlled trials (RCTs) of exercise-based PR in childhood asthma. Language is limited to English. Network meta-analyses and standard meta-analyses were performed using STATA (version 16.0), quality analyses were performed using RevMan (version 5.3). Results: A total of 24 RCTs involving 1031 patients were included. 14 studies were endurance training, which was the most commonly used form of exercise, and 7 studies rehabilitation sites were conducted in hospitals. A network meta-analysis showed that compared with other forms of exercise, interval training significantly improved the PAQLQ (Pediatric Asthma Quality of Life Questionnaire), including activity scores [MD=3.02, 95% CI (1.74,4.30)], symptom scores [MD=2.68, 95% CI (2.04,3.32)], emotional scores [MD=2.47, 95% CI (0.91,4.03)], and total scores [MD=2.68, 95% CI (1.79,3.57)]. Interval training [MD=188.97, 95% CI (-59.27, 437.21)] also had a more significant effect on the 6MWT (6-minute walk test). No adverse events were found in this study. Exercise training had no significant effect on FEV 1(the forced expiratory volume at 1s to predicted value ratio) [WMD=0.59, 95% CI (-2.00, 3.19)], however, the combined of endurance training and respiratory training was found to significantly improve both FVC (the forced vital capacity to predicted value ratio) [MD=5.37, 95% CI (0.07,10.67)] and FEF25-75% (the forced expiratory flow between 25% and 75% of vital capacity ratio) [WMD=11.31, 95% CI (2.13, 20.48)]. Conclusions: Exercise-based PR is a safe and effective for childhood asthma. Interval training may be a core component of improving quality of life and exercise capacity in childhood asthma, the combination of respiratory training and endurance training has significant effects on lung function.This result should be viewed with caution, and high-quality RCTs are still needed to confirm its clinical efficacy,

Background: Observational studies suggest that asthma/wheezing improve after adenotonsillectomy (AT). However, there is a paucity of RCT specifically studying the effects of AT in asthma/wheezing. Therefore, we conducted a post-hoc analysis of the Childhood Adenotonsillectomy Trial, the largest RCT of AT in children with obstructive sleep apnea (OSA) to test the hypothesis that AT would result in fewer wheezing episodes. Methods: In the CHAT study, 464 children with OSA, aged 5 to 9 years, were randomized to early AT (n=226) or watchful waiting with supportive care (WWSC) (n= 227). For this post-hoc analysis children were categorized as having “any wheezing” vs. “no wheezing” at baseline and at 7 months of follow-up. A multivariate analysis was conducted to evaluate the association between “any wheezing” at follow-up and treatment group after controlling for several potential confounders. Results: Children in the “any wheezing” group were predominantly black, had more allergic rhinitis, eczema, second-hand smoke exposure, more siblings and siblings with asthma, lower maternal education and family income than those in the “no wheezing group”. At baseline, wheezing characteristics were similar between AT and WWSC arms. At follow-up (at 7 months of the intervention) those in the AT arm had significatively less wheezing than those in the WWSC (22.4% vs. 43.8%, p=0.00001). However, the multivariate analysis of “any wheezing” vs. “no wheezing” at follow-up showed that the treatment arm was not associated with wheezing. Conclusion: This study demonstrated that AT has not effect on wheezing at 7 months of follow-up.

Through wind tunnel experiments, we measured the structure of surface drifting sand flux and sand transport rate on a bed surface that contained widely but uniformly spaced and non-erodible ridges. We found that under the condition of no ridges, the sand transport rate within the height of 0~70 cm on the bed surface decreases in a power function law with the increase of height, increases with the increase of friction velocity, and the proportion of sand transport rate at different high layers increases with the increase of height. The variation of sand transport rate with height can be divided into two cases for all the ridge heights and spacings: one shows that sand transport rate decreases exponentially with height, while the other shows that sand transport rate increases with height under a certain height, and above the certain height decreases exponentially with the increase of height, known as “elephant nose” effect which seems similar to the structure of drifting sand flux in Gobi desert. For all the ridge heights and spacings, the total sand transport rate in the height of 0~70 cm increases with the increase of friction velocity in a power function law, and increases with the increase of ridge spacing. When the friction velocity and ridge spacing are both large, the total sand transport rate of some ridge structures are larger than that with no ridges. Our results will contribute to the study on recognize the process and mechanism of soil wind erosion in ridge farmland.

Aims: The aim of this study was to evaluate the safety/tolerability, and pharmacokinetics (PKs) of rhEGF eyedrops after administration of a single and multiple doses in healthy subjects. Methods: A phase 1, randomized, double-blind, placebo-controlled, and single ascending dose (SAD) and multiple ascending dose (MAD) study were conducted in 3 dose groups (10, 50, and 100 μg/mL). The subjects randomly received rhEGF eyedrops or their placebo in a 3:1 ratio. Serial blood and tear samples for PK analysis were collected up to 36 h and 180 h post-dose in SAD and MAD study, respectively. In addition, the serum and tear EGF concentrations were measured. Immunogenicity evaluations were conducted using serum anti-EGF antibody level. Results: A total of 50 subjects were enrolled and 48 subjects completed the study. Adverse drug reactions were mild and transient. There were no serious adverse events in this study. The tear EGF concentrations rapidly increased and returned to baseline after 4 hours without serum EGF level change after the administration of rhEGF eyedrops. Conclusion: rhEGF eyedrops were safe and well-tolerated in healthy subjects in a dose range of 10-100 μg/mL, which indicated it was suitable for further studies for corneal injury patients.