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Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

Hyaluronic acid (HA) is a natural polysaccharide that has gained much attention due to its biocompatibility, enzyme degradation capacity and active tumor targeting capacity. Its receptor, CD44, is overexpressed in many kinds of cancers and is associated with tumor progress, infiltration and metastasis. Therefore, many researchers have developed various HA-based drug delivery systems for CD44-mediated tumor targeting. In this review, we systemically overview the basic theory of HA, its receptor and hyaluronidase, then we categorize the studies in HA-based drug delivery systems according to the functions of HA, including tumor-targeting materials, enzyme-sensitive biodegradable modality, pH-sensitive component, reduction-sensitive component, and the gel backbone. Finally, the perspective is discussed. Key words: Hyaluronic acid, Tumor-active targeting, CD44, Tumor microenvironment, Reduction-sensitive, Enzyme-sensitive, Nanoparticles

Abstract: Fetal hemoglobin (HbF) expression is partially governed by the trans-acting quantitative trait loci BCL11A and MYB and a cis-acting locus linked to the HBB gene cluster. Our previous analysis of the Genotype-Tissue Expression database suggested that BCL2L1 was associated with HbF gene expression. In erythroid progenitors from patients with sickle cell disease, BCL2L1 messenger RNA (mRNA) levels were positively correlated with HBG mRNA and total HbF concentration (r 2 = 0.72, P = .047 and r 2 = 0.68, P = .01, respectively). Inhibition of BCL2L1 protein activity in HbF-expressing HUDEP-1 cells decreased HBG expression in a dose-dependent manner. Overexpression of BCL2L1 in these cells increased HBG expression fourfold (P < .05) and increased F cells by 13% (P < .05). Overexpression of BCL2L1 in erythroid progenitors derived from primary adult CD34+ cells upregulated HBG expression 11-fold (P < .05), increased F cells by 18% (P < .01), did not significantly affect cell differentiation or proliferation, and had a minor effect on survival. Although the mechanism remains unknown, our results suggest that BCL2L1 is associated with HbF gene activation.

AIM: To observe the clinical effect of external rectus muscle amputation in the treatment of divergence insufficiency. METHODS: A retrospective analysis of 37 cases of insufficiency in our hospital from February 2011 to October 2017. The clinical manifestations were hyperopic esotropia with ipsilateral diplopia, myopia implicit esotropia without diplopia, and the monocular and binocular movements were normal. Preoperative refractive, strabismus, near stereopsis, negative fusion force examination, and then single or double external rectus muscle surgery.RESULTS: Double vision disappeared after all cases, and there was no recurrence in diplopia after one year of follow-up. The preoperative long-term internal strabismus was +15△-+28△, with an average of 18.4△±5.7△, the near-internal strabismus was +5△-+16△, the average was 10.3△±3.6△, The difference value of long distance and short distance strabismus was 8.1△±2.3△; one week after surgery, the distance strabismus was -5.4△±1.5△, the near-distance squint was -7.2△±1.6△, the difference value was 1.8△±0.6△; the one year postoperative strabismus was -1.9△±1.2△, the close squint was -3.4△±1.4△, the difference value was 1.5△±0.8△. The long-distance strabismus one week after operation and one year after operation was significantly lower than that before operation(PP△-9△, with an average of 5.1△±1.8△, and the near-negative fusion force was 15△-24△, with an average of 19.4△±3.2△. The long-near negative fusion force was 10.1△±3.3△, 19.7△±4.1△ at 1wk after operation, and the long-distance negative fusion force was 11.2△±3.6△, 20.2△±4.8△ for one year after operation. There was a statistically significant difference between the patients with preoperative and one week postoperative negative fusion(q=4.551, P=0.013). There was no significant difference between the one week and one year after surgery(q=0.713, P=0.115).There was no significant difference in the patients' brachytherapy before and after one week and one year after operation(P>0.05).CONCLUSION: Divergence insufficiency of external rectus muscle surgery can effectively reduce the difference of long-distance strabismus after surgery, eliminate the symptoms of diplopia in patients, and improve the near stereoscopic sharpness and long-distance negative fusion force.

Abstract Background The risk of venous thromboembolism (VTE) during pregnancy and puerperal periods is significantly higher than during the non-pregnant period and is one of the major causes of maternal mortality. Developed countries have promulgated guidelines for risk assessment and prevention of maternal VTE, and standardized management has led to a significant reduction in maternal mortality. However, there is a paucity of relevant research related to pregnancy and puerperal VTE in China. Methods/design We will perform a prospective cohort study and recruit 13,000 pregnant women from 2018 to 2020 in Beijing, China. VTE risk assessment will be conducted using the Royal College of Obstetricians and Gynaecologists (RCOG) pregnancy and puerperal VTE risk-assessment-scoring tool during early and late pregnancy, as well as during the puerperal period. Venous ultrasonography of lower extremities, routine blood tests, and coagulation parameters will be examined. These VTE risk assessments will be performed again if patients have VTE-related symptoms during their pregnancies, or if any of the following occur: (1) patients are hospitalized over 7 days due to any pregnancy complications; (2) patients are placed under strict bed rest for ≥ 3 days to prevent miscarriage. For patients with a confirmed diagnosis of VTE, treatment and follow-up plans will be decided jointly by the obstetricians, vascular surgeons, and pulmonologists. All patients in the study will be followed up by dedicated healthcare providers for up to 42 days postpartum. Statistical analyses will be performed to test the feasibility of the RCOG scoring tool for the Chinese population. The RCOG scoring tool will then be revised based upon the characteristics of the Chinese population, and the revised assessment scoring tool will then be tested in the cohort to evaluate its efficacy. Finally, a pregnancy and puerperal VTE risk-assessment tool will be proposed based on our study results. Discussion This study will establish a preliminary VTE risk-assessment tool that is applicable to pregnant and puerperal women in China and provide guidelines for further thrombophylactic interventions. Furthermore, we wish to draw increased attention to pregnancy-associated VTE to reduce VTE-related mortality. Trial registration Chi CTR1800015848 (04/24/2018).

Arrhythmogenic cardiomyopathy (ACM) is a heritable myocardial disease characterized by life-threatening ventricular arrhythmias and sudden cardiac death. Cardiomyocyte death is an essential pathogenic mechanism in ACM, but the cell death landscape has never been elucidated. Our study aimed to address this problem based on RNA-sequencing (RNA-seq) data. Myocardial RNA-seq data from arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and normal controls were obtained from the Gene Expression Omnibus database (GSE107475, GSE107311, GSE107156, GSE107125). Signature gene sets of cell death processes, immune cells, and pathways were collected. Single-sample gene-set enrichment analysis calculated the enrichment scores for these signature gene sets. The RNA-seq data of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from an ACM patient were used for validation (GSE115621). Weighted gene coexpression network analysis (WGCNA) was applied to identify coexpression modules. Immunogenic cell death, apoptosis, necroptosis, and pyroptosis were significantly up-regulated in ARVC. Positive correlations of these four up-regulated cell death processes with immune cells and pathways were found within the ARVC myocardium. In the ARVC sample cluster with higher cell death levels, central memory CD4 T cell, memory B cell, type 1 T helper cell, mast cell, natural killer T cell, and plasmacytoid dendritic cell were more substantially infiltrated. Similarly, immune pathways were more up-regulated in this cluster. Positive linear correlations were found between cell death, immune responses, and myocardial fibrosis within the ARVC samples. Eventually, WGCNA identified a shared coexpression module related to these mechanisms. This study first demonstrated the landscape of cell death processes in the ACM (ARVC) myocardium and their positive correlations with immune responses and myocardial fibrosis. These mechanisms have potential interactions and jointly contribute to the pathogenesis of ACM.

Detecting high-speed and maneuvering targets is challenging in early warning radar applications. Modern early warning radar has many functions such as detection, tracking, imaging, and recognition which need a high signal-to-noise ratio (SNR). Thus, long-time coherent integration is a necessary method to realize high SNR requirements. However, high-speed and maneuverable motion cause range and Doppler migration, which brings about serious coherent integration loss. Traditional integration methods usually have the drawbacks of model mismatching and high computational complexity. This paper establishes a novel long coherent processing interval (CPI) integration algorithm that detects maneuvering and weak targets which have a low reflection cross-section (RCS) and low echo SNR. The range and Doppler migration problems are solved via a layer integration by blending the association in a tracking-before-detection (TBD) technique. Compact SNR gain is achieved with a target information transmission mechanism and an updated constant false alarm ratio (CFAR) threshold. The algorithm is applicable in multiple target scenarios by considering different velocity ambiguities and maneuvers. A simulation and real-measured experiments confirm the effectiveness of the algorithm.

Under the condition of low signal-to-noise ratio, the target detection performance of radar decreases, which seriously affects the tracking and recognition for the long-range small targets. To solve it, this paper proposes a target detection algorithm using convolutional neural network to process graphically expressed range time series signals. First, the two-dimensional echo signal was processed graphically. Second, the graphical echo signal was detected by the improved convolutional neural network. The simulation results under the condition of low signal-to-noise ratio show that, compared with the multi-pulse accumulation detection method, the detection method based on convolutional neural network proposed in this paper has a higher target detection probability, which reflects the effectiveness of the method proposed in this paper.

Objective: This study aimed to construct a prognostic ferroptosis-related signature for thyroid cancer and probe into the association with tumor immune microenvironment.Methods: Based on the expression profiles of ferroptosis-related genes, a LASSO cox regression model was established for thyroid cancer. Kaplan-Meier survival analysis was presented between high and low risk groups. The predictive performance was assessed by ROC. The predictive independency was validated via multivariate cox regression analysis and stratified analysis. A nomogram was established and verified by calibration curves. The enriched signaling pathways were predicted via GSEA. The association between the signature and immune cell infiltration was analyzed by CIBERSORT. The ferroptosis-related genes were validated in thyroid cancer tissues by immunohistochemistry and RT-qPCR.Results: A ferroptosis-related eight gene model was established for predicting the prognosis of thyroid cancer. Patients with high risk score indicated a poorer prognosis than those with low risk score (p = 1.186e-03). The AUCs for 1-, 2-, and 3-year survival were 0.887, 0.890, and 0.840, respectively. Following adjusting other prognostic factors, the model could independently predict the prognosis (p = 0.015, HR: 1.870, 95%CI: 1.132–3.090). A nomogram combining the signature and age was constructed. The nomogram-predicted probability of 1-, 3-, and 5-year survival approached the actual survival time. Several ferroptosis-related pathways were enriched in the high-risk group. The signature was distinctly associated with the immune cell infiltration. After validation, the eight genes were abnormally expressed between thyroid cancer and control tissues.Conclusion: Our findings established a prognostic ferroptosis-related signature that was associated with the immune microenvironment for thyroid cancer.

Aims: To evaluate whether low level left vagus nerve stimulation (LLVNS) in early stage of myocardial infarction (MI) could effectively prevent ventricular arrhythmias (VAs) and protect cardiac function, and explore the underlying mechanisms.Methods and Results: After undergoing implantable cardioverter defibrillators (ICD) and left cervical vagal stimulators implantation and MI creation, 16 dogs were randomly divided into three groups: the MI (n = 6), MI+LLVNS (n = 5), and sham operation (n = 5) groups. LLVNS was performed for 3 weeks. VAs, the left ventricular function, the density of the nerve fibers in the infarction area and gene expression profiles were analyzed. Compared with the MI group, dogs in the MI+LLVNS group had a lower VAs incidence (p < 0.05) and better left ventricular function. LLVNS significantly inhibited excessive sympathetic nerve sprouting with the evidences of decreased density of TH, GAP43 and NF positive nerves (p < 0.05). The gene expression profiling found a total of 206 genes differentially expressed between MI+LLVNS and MI dogs, mainly involved in cardiac tissue remodeling, cardiac neural remodeling, immune response and apoptosis. These genes, including 55 up-regulated genes and 151 down-regulated genes, showed more protective expressions under LLVNS.Conclusions: This study suggests that LLVNS was delivered without altering heart rate, contributing to reduced incidences of VAs and improved left ventricular function. The potential mechanisms included suppressing cardiac neuronal sprouting, inhibiting excessive sympathetic nerve sprouting and subduing pro-inflammatory responses by regulating gene expressions from a canine experimental study.

In this paper, two joints of circular tubed steel-reinforced concrete (CTSRC) column were designed. The load-displacement hysteretic curve and skeleton curve of this new type of joint are obtained by the pseudostatic test under low cycle cyclic load on the top of the column. The results show that this new type of joint has good seismic energy dissipation performance. On the basis of the test, a three-fold skeleton curve model considering three characteristic points of yield, limit, and failure is proposed, and the expression of skeleton curve model is given. The load and unload stiffness degradation law of specimens under reciprocating load is studied, and the expression of stiffness degradation law is given. The hysteresis law of the new type joint specimens is described in detail. The validity of the model is verified by comparing the experimental curve with the model curve. The model can be used in the elastic-plastic seismic time-history analysis on the joint of circular tubed steel-reinforced concrete (CTSRC) column.

A new type joint of Circular Tubed Steel-Reinforced Concrete (CTSRC) columns was designed in this paper. The structural characteristics, manufacturing process, and mechanical properties of raw materials of the new joint were introduced. In order to simulate the earthquake action, two joint specimens were subjected to low-cycle cyclic loading at the end of the column. Based on the in-depth study of the failure characteristics, load-displacement hysteretic curve, skeleton curve, ductility index, load-strain hysteretic curve in the core area of the joint, energy dissipation performance, strength and stiffness degradation performance, and shear deformation in the core area of the joint during the whole loading process, the seismic behavior of this new type of joint was investigated. The results show that the new joint has reasonable failure characteristics, high bearing capacity, good ductility, excellent seismic energy dissipation performance, and strong resistance to strength and stiffness degradation, which meets the seismic design principle of “strong joint and weak component” and is suitable for the results with special requirements for seismic performance. In addition, preliminary design recommendations were put forward. The research results of this paper can provide a theoretical basis for the application of this kind of new structure.

Rice production involves abundant water and fertilizer inputs and is prone to nitrogen (N) loss via surface runoff and leaching, resulting in agricultural diffuse pollution. Based on a two-season paddy field experiment in Jiangsu Province, China, field water and N dynamics and their balances were determined with the well-calibrated HYDRUS-1D model. Then, scenarios of different controlled drainage and N fertilizer applications were simulated using the HYDRUS-1D model to analyze the features and factors of N loss from paddy fields. Evapotranspiration and deep percolation were the two dominant losses of total water input over the two seasons, with an average loss of 50.9% and 38.8%, respectively. Additionally, gaseous loss of N from the whole soil column accounted for more than half of total N input on average, i.e., ammonia volatilization (17.5% on average for two seasons) and denitrification (39.7%), while the N uptake by rice accounted for 37.1% on average. The ratio of N loss via surface runoff to total N input exceeded 20% when the N fertilizer rate reached 300 kg ha−1. More and longer rainwater storage in rice fields under controlled drainage reduced surface runoff losses but increased the risk of groundwater contamination by N leaching. Therefore, compared with raising the maximum ponding rainwater depth for controlled drainage, optimizing N fertilizer inputs may be more beneficial for controlling agricultural diffuse pollution by reducing N loss via surface runoff and leaching. The HYDRUS-1D model provides an approach for the quantitative decision-making process of sustainable agricultural water and N management.

To optimize suitable water-saving and soil salt-controlling irrigation needed for the high yield and good quality of cotton in southern Xinjiang, a field experiment was carried out to study the effects of soil water lower limits on water consumption, water use efficiency (WUE), yield, cotton fiber quality and soil salt accumulation under mulched drip irrigation in Korla, Xinjiang. The field capacity (FC) was regarded as the upper limit of soil moisture, and five soil water lower limits (85% FC, 75% FC, 65% FC, 55% FC, 45% FC, referred as T1~T5, respectively) were designed during the cotton growth period. The results indicated that the irrigation frequency and irrigation quota of cotton were gradually increased with the increase in the soil water lower limit, while the water consumption modulus for T2 treatment during the critical period of water demand arrived at the maximum value. Moreover, with the decrease in the soil water lower limit, the WUE, fiber micronaire value and fiber maturity index of cotton increased, whereas the yield, nitrogen partial factor productivity (PFPN) and fiber breaking elongation of cotton decreased. However, when the soil water lower limit exceeded 75% FC, the increase had little effect on the cotton yield increase and PFPN improvement, and the yield and PFPN for T2 treatment were 7146.4 kg∙hm−2 and 23.82 kg∙kg−1, respectively, In addition, the decrease in the soil water lower limit was unfavorable for an increase in fiber length, but it was conducive to the enhancement of fiber strength. Furthermore, soil salt accumulated inside and outside the film for the designed soil water lower limits, and the amount of accumulated salt in 0~100 cm followed T3 > T5 > T1 > T2 > T4. Based on a comprehensive analysis with the entropy TOPSIS method, the findings of the present study suggested that the suitable soil water lower limit for cotton under mulched drip irrigation was 75% FC in southern Xinjiang, China.

Circular RNAs (circRNAs) are regarded as pivotal regulators in bone metabolism. However, the role of circRNAs in osteoblast mineralization remains largely unknown. Herein, we explored the expression profiles of circRNAs in 4 groups of osteoblasts with varying mineralization processes. Hsa_circ_0008500 (circ8500), which is upregulated in the RNA-seq data, is sifted through 194 candidate circRNAs in osteoblasts during mineralization. We characterize the features of novel circRNAs and find that the elevated expression of circ8500 promotes osteoblast mineralization. Mechanistically, circ8500 contains a critical binding site for miR-1301-3p. We further show that circ8500 competitively binds miR-1301-3p to abolish its suppressive effect on peptidyl arginine deiminase 4 (PADI4). PADI4 works as a binding partner of RUNX2 and stabilizes its protein expression levels by inhibiting the ubiquitin-proteasome pathway. This work provides new insights on the circRNA patterns in osteoblasts and the role of PADI4 in matrix mineralization.

Abstract It has been reported that Cavin1 deficiency causes lipodystrophy in both humans and mice by affecting lipid metabolism. The ablation of Cavin1 in rodents also causes a significant deviation from Mendelian ratio at weaning in a background‐dependent manner, suggesting the presence of undiscovered functions of Cavin1. In the current study, the results show that Cavin1 deficiency causes neonatal death in C57BL/6J mice by dampening the storage and mobilization of glycogen in the liver, which leads to lethal neonatal hypoglycemia. Further investigation by electron microscopy reveals that Cavin1 deficiency impairs the fenestration in liver sinusoidal endothelial cells (LSECs) and impacts the permeability of endothelial barrier in the liver. Mechanistically, Cavin1 deficiency inhibits the RhoA‐Rho‐associated protein kinase 2‐LIM domain kinase‐Cofilin signaling pathway and suppresses the dynamics of the cytoskeleton, and eventually causes the reduction of fenestrae in LSECs. In addition, the defect of fenestration in LSECs caused by Cavin1 deficiency can be rescued by treatment with the F‐actin depolymerization reagent latrunculin A. In summary, the current study reveals a novel function of Cavin1 on fenestrae formation in LSECs and liver glycogen metabolism, which provide an explanation for the neonatal death of Cavin1 null mice and a potential mechanism for metabolic disorders in patients with Cavin1 mutation.

Abstract Herein, two water‐soluble PROXYL‐based magnetic resonance imaging (MRI) macromolecular organic contrast agents (mORCAs) are designed and synthesized: linear and cross‐linked PCE‐mPEG‐Ppa‐PROXYL. They are prepared by conjugating linear and cross‐linked poly(carboxylate ester) (PCE) with poly(ethylene glycol) (mPEG2000)‐modified nitroxides (PROXYL), respectively. Both mORCAs form self‐assembled aggregates in an aqueous phase and PROXYL is protected inside a hydrophobic core to achieve great resistance to reduction in the physiological environment, and they have low toxicity. Since cross‐linked PCE‐mPEG‐Ppa‐PROXYL possess a branched architecture, its self‐assembled aggregate is more stable and compact with a greater particle size. Cross‐linked PCE‐mPEG‐Ppa‐PROXYL outperform the linear one in the following aspects: 1) its longitudinal relaxivity (r1 = 0.79 mm−1 s−1) is higher than that of the linear one (r1 = 0.64 mm−1 s−1) and both excel the best mORCA reported so far (r1 = 0.42 mm−1 s−1); 2) its blood retention time (≈48 h) is longer than that of its linear counterpart (≈10 h); 3) cross‐linked PCE‐mPEG‐Ppa‐PROXYL provided better MR imaging contrast resolution in normal organs (liver and kidney) and tumor of mice than the linear one. Overall, cross‐linked PCE‐mPEG‐Ppa‐PROXYL may have great potential to be a novel metal‐free macromolecular contrast agent for MR imaging.

Loess is a special geotechnical material with strong structural properties, and the microstructural characteristics of loess significantly influence its macroscopic physical features, mechanical properties, and catastrophic behavior. In this paper, serial samples were extracted from the continuous loess and paleosol strata of the Bai Lu tableland; with these samples, the optical microscopy-based serial sectioning method was adopted to study the quantitative characterization and variation in the loess microstructure. Three-dimensional characteristics and quantitative parameters of the particles, pores, and throats of the loess were obtained. The results indicate that the volume, Eq-Radius, and major-minor axis ratio of the loess particles satisfy third-order, third-order, and second-order Gaussian distributions, respectively. The Eq-Radius of the loess pores and throats satisfies a first-order Gaussian distribution, and the throat channel length satisfies a gamma distribution. With increasing stratum depth, the particles become more flattened, the throat radii become larger and the pore channels become slenderer. The variation in fitting parameters and the correlations between the macrophysical and mechanical properties of loess were then explored. The study of the microstructure of loess contributes to a better understanding of the catastrophic behavior of loess and the physical mechanism of geologic hazards in this area.

AIM: To observe the change of axial length in anisometropia myopia with simple eye receiving orthokeratology treated.METHODS: Totally 56 cases(112 eyes)with anisometropia myopia receiving monocular orthokeratology treated were divided into two groups. For every case, eye wearing orthokeratology was assigned to the experimental group and another eye to the control group. The refraction, corneal curvature and axial length were measured at pre-wear and 1mo discontinuation after wearing orthokeratology 1y.RESULTS: The statistically significant changes(t=2.8631, Pt=0.8204, P>0.05). The increase of axial length was(0.14±0.10)mm and(0.32±0.14)mm for the experimental and control group, respectively, and the increase was statistically significant(t=2.7518,PCONCLUSION: Orthokeratology can slow down myopia progression by reducing axial length to control myopia increase.

AIM: To appraise the effect of treatment for diabetic macular edema (DME) in proliferative stage with sufficient panrentinal photocoagulation (PRP) therapy and intravitreal injections (IV) Conbercept and posterior subtenon’s triamcinolone acetonide (STTA) sequential therapy. METHODS: This prospective clinical randomized controlled trial of cross-over design was conducted in three phases. The participants included cases of DME in proliferative stage. They were divided into two groups and treated with PRP before enrollment. Group A were treated with IV-Conbercept 0.5 mg for one month in the 1st phase. Group B were treated with STTA 40 mg (twice per two weeks). The interventions were exchanged in the second phase (2mo) between the two groups. In the third phase (3-6mo) no other treatment was given. Best corrected visual acuity (BCVA), central macular thickness (CMT) measured by OCT and complications were compared. RESULTS: After phase I: in Group A, BCVA improved from 0.201±0.17 to 0.37±0.24 (F=5.88, P=0.004). CMT changed from 449±155.10 to 304.1±84.70 μm (F=14.9, P0.05). After phase III: in Group A, BCVA maintained 0.42±0.25 (F=0.22, P=0.001), CMT maintained 267.8±58.34 μm, (F=-0.27, P

This study investigated the influence of students' different Online Learning Readiness (OLR) profiles on their Online Self-Regulated Learning (OSRL) strategies in the context of the first online learning experience (FOL) for students. The data was collected from 262 students in a four-year university in North China during the Spring of 2021. K-mean cluster analysis was conducted to identify groups of participants with distinct patterns of OLR, and one-way MANOVA was used to determine the difference in online OSRL between the different groups. The findings reveal that FOL students with greater levels of OLR also possessed higher levels of OSRL, including goal setting, environmental structuring, task strategies, time management, help-seeking, and self-evaluation. On the basis of the findings, the authors address the function of OLR in establishing OSRL in online learning and its implications for supporting FOL students' self-regulated learning in online learning. The study underlines the need of educating college students in China to succeed in online learning throughout the transition from the COVID-19 global pandemic to the post-pandemic period.

Triptolide and celastrol are predominantly active natural products isolated from the medicinal plant Tripterygium wilfordii Hook F. These compounds exhibit similar pharmacological activities, including anti-cancer, anti-inflammation, anti-obesity, and anti-diabetic activities. Triptolide and celastrol also provide neuroprotection and prevent cardiovascular and metabolic diseases. However, toxicity restricts the further development of triptolide and celastrol. In this review, we comprehensively review therapeutic targets and mechanisms of action, and translational study of triptolide and celastrol. We systemically discuss the structure-activity-relationship of triptolide, celastrol, and their derivatives. Furthermore, we propose the use of structural derivatives, targeted therapy, and combination treatment as possible solutions to reduce toxicity and increase therapeutic window of these potent natural products from T. wilfordii Hook F.

Cadmium exposure can cause renal tubular dysfunction. Recent studies show that vitamin D can play multiple roles in the body. However, the association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium has not been clarified. We performed study to assess the effects of cadmium on serum 25(OH) D levels and the association between serum 25(OH) D levels and renal tubular dysfunction in a population environmentally exposed to cadmium. A total of 133 subjects living in control area and two cadmium polluted areas were included in the present study. Cadmium in urine (UCd) and blood (BCd), urinary β2Microglobulin (UBMG), urinary retinol binding protein (URBP) and serum 25 (OH) D were determined. Logistic regression was used to estimate the association between 25 (OH) D and prevalence of renal tubular dysfunction. No significant differences were observed in serum 25(OH) D levels among the four quartile of UCd and BCd after adjusting with cofounders. After adjusted with the confounders, the odds ratio (OR) of subjects with 25(OH) D ≥ 40 ng/ml were 0.20 (95%CI: 0.1-0.8) if UBMG was chosen as indicators of renal dysfunction and 0.28 (95%CI: 0.1-1.1) if URBP was chosen as indicators of renal dysfunction, compared with those with 25(OH) D < 30 ng/ml, respectively. Similar results were observed in those subjects living in cadmium polluted areas or with high level of UCd or BCd. Our data indicated that cadmium exposure did not affect serum 25(OH) D level and high 25 (OH) D levels were associated with a decreased risk of renal tubular dysfunction induced by cadmium.

Intrahepatic cholestasis is a serious symptom of liver disorders with limited therapies. In this study, we investigated the efficacy of Huangqi decoction (HQD), a two-herb classic traditional Chinese medicine (TCM), in the treatment of alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. HQD treatment ameliorated impaired hepatic function and tissue damage. A metabolomics study revealed that the endogenous metabolites significantly affected by HQD were related to bile acid (BA) biosynthesis and glutathione metabolism pathways. HQD treatment decreased the intrahepatic accumulation of cytotoxic BAs, normalized serum BA levels, and increased biliary and urinary BA excretion. Additionally, HQD restored the hepatic glutathione content and suppressed reactive oxygen species (ROS) in cholestatic mice. Protein and gene analysis revealed that HQD increased the expression of the hepatic metabolizing enzymes cytochrome P450 (CYP) 2B10 and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), as well as multidrug resistance-associated protein 2 (Mrp2), Mrp3, and Mrp4, which play crucial roles in BA homeostasis. Further, HQD increased the protein expression of glutamate-cysteine ligase, which is involved in the synthesis of glutathione. Importantly, HQD increased the nuclear expression of nuclear factor-E2-related factor-2 (Nrf2). In conclusion, HQD protects against intrahepatic cholestasis by reversing the disordered homeostasis of BAs and glutathione.

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

AIM: To observe the clinical effect of super quantity of binocular medialrectus in treating large angle concomitant esotropia.METHODS: Eighty-one patients with large angle concomitant esotropia were analyzed retrospectively. According to the operation method, they had been divided into observation group(large recession of rectus muscle)and control group(normal recession of rectus muscle). The number of muscle were evaluated, eye's position and involution function in a week and a year after operation were also evaluated.RESULTS:Forty-three cases in observation group had binocular medial rectus treatment, while 5 cases had binocular medial rectus+monocular medial rectus muscle resection treatment. Six cases in control group had the surgical treatment of bilateral medial rectus recession, 21 cases had binocular medial rectus+monocular medial rectus muscle resection and 6 cases with binocular medial rectus+bilateral lateral rectus shortening. The difference of the muscles' numbers of two groups in operation had statistical significance(χ2=41.72, P△～+12△, the average was +6.52△±3.23△, while that of control group was -3△～+10△, the average was +5.38±2.46△. The difference of two groups had no statistical significance(t=1.45, P=0.08). One year after operation, eye positions of observation group and control group were -5△～+10△(average: +4.57△±2.71△)and -5△～+8△(average: +3.92△±2.15△). The difference of two group had no statistical significance(t=1.23, P=0.10). One week after the operation, 14 cases of observation group and 6 cases of control group's involution function were limited. One year after operation, 5 cases of observation group and 2 cases of control group's involution function were limited. The differences of two group had no statistical significance(χ2=1.27, P>0.05; χ2=0.47, P>0.05).CONCLUSION: Super quantity of medial rectus recession in treating large angle concomitant esotropia can reduce the muscle's number, but it has no obvious influence on eyeball's involution function.

AIM:To observe the effects of operative treatment for muscular asthenopia caused by esophoria. METHODS:Twenty-one cases(42 eyes)with muscular asthenopia caused by esophoria were included. After examination of refraction, phoria and fusion function, all cases were given operative treatment to correct esophoria. RESULTS:At 1wk after surgery, clinical symptoms were improved evidently in all cases, such as headache, diplopia and eye swelling. After followed up for 1a, no recrudescence was found. Before surgery, at 1wk and 1a after surgery, esophoria in the distance were 20.3△±6.3△,-3.1△±1.4△,0.7△±1.6△ respectively and esophoria in the near distance were 10.5△±3.1△,-1.3△±0.6△,1.5△±0.8△ respectively. By comparison of esophoria before and after surgery in different stages separately, the differences were statistically(PP>0.05). CONCLUSION:Esophoria operation may relieve obviously muscular asthenopia caused by esophoria without changing fusion function.

The number of kidney podocytes is reduced in diabetic nephropathy. Advanced glycation end products (AGEs) accumulate in patients with diabetes and promote the apoptosis of podocyte by activating the forkhead box O4 (Foxo4) transcription factor to increase the expression of a pro-apoptosis gene, Bcl2l11. Using chromatin immunoprecipitation we demonstrate that AGE-modified bovine serum albumin (AGE-BSA) enhances Foxo4 binding to a forkhead binding element in the promoter of Bcl2lll. AGE-BSA also increases the acetylation of Foxo4. Lysine acetylation of Foxo4 is required for Foxo4 binding and transcription of Bcl2l11 in podocytes treated with AGE-BSA. The expression of a protein deacetylase that targets Foxo4 for deacetylation, sirtuin (Sirt1), is down regulated in cultured podocytes by AGE-BSA treatment and in glomeruli of diabetic patients. SIRT1 over expression in cultured murine podocytes prevents AGE-induced apoptosis. Glomeruli isolated from diabetic db/db mice have increased acetylation of Foxo4, suppressed expression of Sirt1, and increased expression of Bcl2l11 compared to non-diabetic littermates. Together, our data provide evidence that alteration of Foxo4 acetylation and down regulation of Sirt1 expression in diabetes promote podocyte apoptosis. Strategies to preserve Sirt1 expression or reduce Foxo4 acetylation could be used to prevent podocyte loss in diabetes.

AIM: To observe the clinical effect of modified tightening operation of orbicularis combined with lower eyelid retractor muscle aponeurosis suture in the treatment of senile entropion, and to improve reference for clinical treatment planning. METHODS:A retrospective analysis from August 2009 to August 2012, 218 cases of patients with lower eyelid entropion were treated in our hospital, according to the different operation methods for the observation group 128 cases and control group with 90 cases. The observation group was treated with modified tightening operation of orbicularis combined with lower eyelid retractor muscle aponeurosis suture, control group with suture plus margin incision for treatment. Follow-up of two groups were 1a, the clinical curative effect at 1mo and 1a postoperatively was observed. RESULTS: The observation group healed in 124 cases at 1mo after operation, the cure rate was 96.9%, the control group cured 84 cases, the cure rate was 93.3%. The differences of cure rate in two groups were not statistically significant(P>0.05); the observation group healed in 111 cases at 1a after operation, the cure rate was 86.7%, the control group cured 58 cases, the cure rate was 64.4%, the recovery rate of observation group was significantly higher than the control group(PCONCLUSION:The modified senile entropion operation has good curative effect, and the operation is simple, the recurrence rate is low, it is worth popularizing.

AIM: To summarize common causes and coping strategy for complications after muscle surgery in restricted strabismus caused by thyroid associated ophthalmopathy(TAO). METHODS:It was retrospective study. Totally 21 cases after muscle surgery in restricted strabismus caused by TAO, hospitalized from January 2009 to February 2012, were analyzed, including patient's condition, extraocular muscle surgery, complications of surgery. RESULTS: Totally 6 cases with hypertropia and 15 cases with hypotropia before operation were observed. The strabismus surgery included myectomy of superior rectus(1 case), recession of superior rectus(5 cases), and recession of inferior rectus muscle(15 cases). Two cases were found injury of sclera, 1 case while cutting off muscle stop and another while suturing and 3 cases were found preset stitches slipped during operation. Undercorrection happened in 6 cases and overcorrection in 5 cases in the early stage after operation(within a month). Overcorrection was in 15 cases(6 cases with restricted hypertropia and 9 cases with restricted hypotropia)and lower eyelid retreat in 8 cases in the late postoperative period(6 months after operation).CONCLUSION:Overcorrection tends to occur after muscle surgery in restricted strabismus caused by TAO. Quantity of recession of muscle should be strictly controlled during the surgery. Lower eyelid retreat may occur in recession of inferior rectus muscle.

AIM: To analyze the effect of pneumatic retinopexy used in unsuccessful scleral buckling surgeries which failed because of missing holes, new breaks and so on. METHODS: A case control study was done, 32 unsuccessful scleral buckling paients(32 eyes)in our hospital from 2010 to 2012, who match condition of pneumatic retinopexy were divided into two groups in random. The observation group were cured by pneumatic retinopexy, the control group were cured by vitrectomy combined with gas. The cure rate, corrected visual acuity, hospitalization costs and satisfaction rate were recorded to be contrasted. RESULTS: The cure rate of both group were high, the observation group was 93.8%(15/16),the control group was 87.5%(14/16). The corrected visual acuity of the two groups respectively were 4.72±0.12, 4.75±0.14. They had no difference in statistic. But the observation group was far less than the control group in hospitalization costs, they were 4 543±126 yuan and 12 367±138 yuan respectively, and it got higher satisfaction rate than the control group, they were 93.8% and 62.5%. Both index had difference in statistic(PCONCLUSION: The pneumatic retinopexy used in unsuccessful scleral buckling surgeries can improve cure rate, satisfaction rate and it can bring down in hospitalization costs.