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The incidence of myopia is gradually on the rise worldwide, which seriously affects the eye health of teenagers and children, causing enormous loss of socioeconomic benefits. As a result, the prevention and control of myopia is crucial and urgent. In recent years, orthokeratology lens have gradually demonstrated its superiority in the field of myopia prevention and control. At present, the principle of controlling the development of myopia by orthokeratology lens is mainly based on the theory of retinal hyperopia optical defocus, which promotes the shift of hyperopic defocus to myopic defocus in myopic patients to curb the growth of the axial length. The effect of controlling the development of myopia is related to various factors, including the total amount of defocusing, pupil diameter, optical zone design, and lens decentration. The widespread use of orthokeratology lenses will effectively reduce the incidence of myopia in teenagers and children. This paper discusses the principle of controlling the development of myopia by the defocus technique of orthokeratology lenses, and the relationship between the amount of defocusing and the position of the defocusing circle and the effect of myopia prevention and control. A specific review was conducted to clarify the research progress on defocus technique of orthokeratology lens in the prevention and control of myopia.
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Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×104, and the effective concentration of the positive drug was 1-100 µmol·L-1. In addition, pretreated with 10 µmol·L-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.
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Background Dibutyl phthalate (DBP) is a common plasticizer in daily life and has been proved to be related to the exacerbation of allergic asthma. Domestic and foreign studies have shown that lipid peroxidation is closely related to the severity of asthma, which can be used as a basis for the diagnosis and treatment of asthma. Whether DBP can induce lipid peroxidation in allergic asthma remains to be further studied. Objective To investigate whether DBP aggravates allergic asthma by inducing lipid peroxidation in allergic asthma mice. Methods Eighty male BALB/c mice were randomly divided into 4 groups, namely control group, DBP group (40 mg·kg−1), 50 μg ovalbumin (OVA) group (allergic asthma model group), and DBP+OVA group. The DBP group and the DBP+OVA group were given DBP by gavage from Day 1 to 28, and the OVA group and the DBP+OVA group were sensitized by intraperitoneal injection of OVA, once every 3 d, a total of 5 injections, from Day 9 to 21. From Day 29 to 35, the OVA group and the DBP+OVA group were challenged by OVA atomization. After the exposure, samples of blood and lung were collected. The airway hyperresponsiveness of mice was observed by lung function analysis. The serum contents of immunoglobulin E (IgE), OVA-specific immunoglobulin E (OVA-IgE), and lung homogenate levels of interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay (ELISA) to evaluate airway allergic inflammation. The pathological changes of lung tissues were observed after hematoxylin-eosin (HE) staining and collagen fiber (Masson) staining. The contents of reactive oxygen species (ROS), lipid ROS, glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung homogenates were detected by ELISA to evaluate lipid peroxidation. Results The results of lung function analysis showed that compared with the control group, the inspiratory resistance (Ri) and expiratory resistance (Re) of the OVA group and the DBP+OVA group were increased, and the lung compliance (Cldyn) was decreased. The DBP + OVA group was more severe, and the difference between the OVA group and the DBP + OVA group was statistically significant (P<0.05 or P<0.01). Compared with the control group, the contents of IgE, OVA-IgE, and IL-4 in the OVA group and the DBP+OVA group were increased (P<0.05 or P<0.01), which indicated more severe allergic airway inflammation. The HE sections of the OVA group and the DBP+OVA group showed inflammatory cell infiltration around the airway, airway wall hyperplasia and thickening, and severe airway deformation, and the presentation of the DBP+OVA group was the most serious. After Masson staining, the OVA group and the DBP+OVA group showed depositions of a large number of collagen fibers, and the blue collagen fibrosis in the DBP+OVA group was even more serious. ROS, lipid ROS, MDA, and 4-HNE levels increased and GSH and GPX4 levels decreased in the OVA and DBP+OVA groups (P<0.05 or P<0.01), with the most severe effect in the DBP+OVA group. Conclusion DBP may induce lipid peroxidation in mice allergic asthma by producing excessive ROS which may aggravate the allergic asthma in mice.
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Manganese plays an important physiological role in the organism, and excessive manganese exposure can cause impairment of neurological and reproductive functions. Gonadotropin-releasing hormone secreted by the hypothalamus acts as an initiator to regulate reproductive functions, such as gonadal development, onset of puberty, and gonadal hormone release. But the mechanism by which manganese damages the hypothalamus leading to abnormal gonadotropin-releasing hormone release is still unclear yet. Kisspeptin, prostaglandin E2, and nitric oxide may act as stimulators to increase the release of gonadotropin-releasing hormone, while the stimulatory or inhibitory effect of γ-aminobutyric acid on the release of gonadotropin-releasing hormone is controversial. Based on current research, manganese has been less studied with Kisspeptin, and studies with prostaglandin E2, nitric oxide, and γ-aminobutyric acid mainly focused on inflammation, oxidative stress, and neurotransmitter transmission. Therefore, taking Kisspeptin, prostaglandin E2, γ-aminobutyric acid, and nitric oxide as the breakthrough points, this paper introduced the mechanism of manganese affecting the release of gonadotropin-releasing hormone in the hypothalamus through the above four pathways, and proposed that the abnormal release of gonadotropin-releasing hormone in the hypothalamus may be one of the mechanisms by which manganese regulates reproductive function, providing a new direction for the prevention and treatment of manganese-induced reproductive damage in the future.
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AIM: To evaluate the changes of retinal microvascular density in patients with sellar region tumor, and its correlation with the damage to visual field, and to explore its application value in evaluating optic nerve injury of those patients.METHODS: Cross-sectional study. A total of 157 patients(292 eyes)with sellar region tumor, including 82 cases(152 eyes)of pituitary adenoma and 75 cases(140 eyes)of craniopharyngioma, were selected from neurosurgery department and ophthalmology department of Beijing Tiantan Hospital, Capital Medical University between October 2018 and May 2022. A total of 90 people(180 eyes)during the same period, including the family members of patients, students and staff in Beijing Tiantan Hospital, Capital Medical University were collected as control group. All participants underwent optical coherence tomography angiography(OCTA)examination. The changes of retinal microvascular density and its correlation with visual field parameters were compared between the two groups.RESULTS: In patients with sellar region tumor, the radial peripapillary capillary(RPC)and superficial retinal capillary plexus(SRCP)density were significantly lower than that in the control group [50.81%(46.49%, 53.49%)vs. 52.78%(50.73%, 54.51%)and 50.57%(48.13%, 52.73%)vs. 51.63%(49.78%, 53.02%), all P<0.05]. The RPC density in the craniopharyngioma group was lower than that in the pituitary adenoma group [49.71%(44.33%, 53.14%)vs. 51.37%(47.42%, 53.95%), P<0.05]. The MD, PSD and VFI of the sellar region tumor group were -4.33(-12.22, -1.85)dB, 3.37(1.91, 8.82)dB and 92%(65%, 97%)respectively. RPC density of patients with sellar region tumor was positively correlated with MD and VFI, and was negatively correlated with PSD. The SRCP density of each quadrant was positively correlated with MD, and was positively correlated with VFI except Para-T and it was negatively correlated with PSD(all P<0.05).CONCLUSION: Retinal microvascular changes were present in patients with sellar region tumor. Lower vessel density indicates more severe damage to visual field. In the clinic, visual field examinations combined with OCTA were helpful to find the optic nerve injury of patients.
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AIM: To establish an intelligent diagnostic model of keratoconus for small-diameter corneas by data mining and analysis of patients' clinical data.METHODS: Diagnostic study. A total of 830 patients(830 eyes)were collected, including 338 male(338 eyes)and 492 female(492 eyes), with an average age of 14-36(23.19±5.71)years. Among them, 731 patients(731 eyes)had undergone corneal refractive surgery at Chongqing Nanping Aier Eye Hospital from January 2020 to March 2022, and 99 patients had a diagnosed keratoconus from January 2015 to March 2022. Corneal diameter ≤11.1 mm was measured by Pentacam in all patients. Two cornea specialists classified patients' data into normal corneas, suspect keratoconus, and keratoconus groups based on the Belin/Ambrósio enhanced ectasia display(BAD)system in Pentacam. The data of 665 patients were randomly selected as the training set and the other 165 patients as the validation set by computer random sampling method. Seven parametric corneal features were extracted by convolutional neural networks(CNN), and the models were built by Residual Network(ResNet), Vision Transformer(ViT), and CNN+Transformer, respectively. The diagnostic accuracy of models was verified by cross-entropy loss and cross-validation method. In addition, sensitivity and specificity were evaluated using receiver operating characteristic curve.RESULTS: The accuracy of ResNet, ViT, and CNN+Transfermer for the diagnosis of normal cornea and suspect keratoconus was 85.57%, 86.11%, and 86.54% respectively, and the area under the receiver operating characteristic curve(AUC)was 0.823, 0.830 and 0.842 respectively. The accuracy of models for the diagnosis of suspect keratoconus and keratoconus was 97.22%, 95.83%, and 98.61%, respectively, and the AUC was 0.951, 0.939, and 0.988 respectively.CONCLUSION: For corneas ≤11.1 mm in diameter, the data model established by CNN+Transformer has a high accuracy rate for classifying keratoconus, which provides real and effective guidance for early screening.
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Intermittent exotropia(IXT)is a common ophthalmic disease with high incidence, variable deviation, and varying degrees of impaired binocular visual function. The defect of binocular visual function is related to the changes of visual cortex. IXT involves the functional changes of many brain regions, including the cortical areas related to binocular fusion. After correcting the eye position, the abnormal changes of cerebral cortex still exist in some patients with IXT, and the recovery of binocular vision is still difficult. In order to solve these problems, visual perception training is gradually applied to the postoperative reconstruction of binocular visual function in patients with IXT. Visual perception training repairs the visual cortex from the brain level, improving the ability of the visual cortex to process information by constantly stimulating the visual center, thus repairing the visual central function, so that patients can obtain good binocular visual function, stabilize the eye position and reduce recurrence. This article reviews the mechanism of binocular visual impairment and the role of visual perception training in the treatment of IXT. It is hoped to provide more evidence for visual perception training to reconstruct postoperative binocular visual function and reduce the recurrence rate in patients with IXT.
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Objective To analyze the equity and efficiency of resource allocation for management and treatment of severe mental disorders in Shanghai in 2020, and to provide a foundation for making relevant policies. Methods Data on resource allocation for the management and treatment of severe mental disorders in 17 district-level mental health institutions in 2020 were collected. The Gini coefficient was used to evaluate the equity of resource allocation by population and geographic area, and data envelopment analysis was carried out to analyze the equity of resource allocation. Results The Gini coefficients of special funds, psychiatric medical staff and actual open beds according to population were 0.24, 0.25 and 0.27, respectively. The Gini coefficients according to area were 0.54, 0.62 and 0.64, respectively. The average efficiency of resource allocation was 0.865. There were 5 institutions where DEA was effective, accounting for 29.41%. There were 12 institutions where DEA was non-effective, accounting for 70.59%. Conclusion The equity of resources allocation for the management and treatment of severe mental disorders according to population is good, but the equity of allocation based on geographic area is not high. The efficiency of resource allocation needs to be further improved. It is suggested that the resource allocation should be optimized to promote the fairness and efficiency of resource allocation for the management and treatment of severe mental disorders.
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Objective:To learn about the epidemiological and spatial clustering characteristics of brucellosis in Shandong Province, and to provide a reference for scientific prevention and control of brucellosis.Methods:The epidemic data of human brucellosis in Shandong Province from January 2015 to December 2020 were collected from the Infectious Disease Reporting Information Management System of China Disease Control and Prevention Information System, and the data were analyzed by descriptive epidemiology and spatial clustering analysis.Results:A total of 18 811 cases of human brucellosis were reported in Shandong Province from 2015 to 2020, and the average annual incidence rate was 3.16/100 000. Human brucellosis occurred in every month of the year, and the peak incidence was from March to August, accounting for 66.31% (12 474/18 811). The top 5 counties (districts) with average annual incidence rates were Lijin County (32.39/100 000), Kenli District (11.02/100 000), Wudi County (10.35/100 000), Zhanhua District (9.59/100 000) and Shanghe County (8.80/100 000). There were 13 436 males and 5 375 females, with a male-female sex ratio of 2.50 ∶ 1.00; the age was mainly concentrated in 30-69 years old, accounting for 83.23% (15 656/18 811); farmer was the main occupation, accounting for 85.82% (16 144/18 811). The results of global spatial autocorrelation analysis showed that the annual incidence rates of brucellosis in Shandong Province showed a spatial clustering distribution from 2015 to 2020; and the local spatial autocorrelation analysis showed that the high incidence of human brucellosis was mainly concentrated in the north of Shandong Province.Conclusions:The incidence of brucellosis in Shandong Province is mainly concentrated in spring and summer, most of them are farmers, and the high incidence areas have spatial clustering. Key prevention and control measures should be taken for high incidence seasons, high-risk population and northern high clustering areas to reduce the incidence of brucellosis.
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Objective:To investigate the mediating effect of hope on resilience and post traumatic growth (PTG) in patients with refractory secondary hyperparathyroidism (rSHPT).Methods:It was convenient to select rSHPT patients and non-refractory SHPT patients who received maintenance hemodialysis treatment in China-Japan Friendship Hospital from September 2018 to September 2021. Totally 495 patients with rSHPT and 1 295 patients with mild secondary hyperparathyroidism (SHPT) were surveyed by the Chinese Version of The Herth Hope Scale, the Chinese version of the Connor-Davidson Resilience Scale and the Post Traumatic Growth Rating Scale (PTGI). After matching according to the 1∶1 Propensity Score Matching (PSM), 436 cases were set in each of the two groups. The differences of hope, resilience and PTG scores between the two groups were compared. Pearson correlation analysis was used to analyze the correlation between hope, resilience and total score of PTG in rSHPT group. Regression analysis and SPSS Process mediation Model 4 were used to test the mediating effect of hope on resilience and PTG.Results:The hope score (32.16 ± 4.15), psychological resilience score (61.22 ± 14.38), and the PTG score (52.34 ± 18.92) of rSHPT patients was significantly lower than 33.41 ± 2.97 ( t=-5.72, P<0.05), 63.19 ± 7.25 ( t=-2.77, P<0.05), 57.95 ± 10.07 ( t=-6.34, P<0.05) of SHPT patients. There was a positive correlation between hope, resilience and PTG score ( r=0.671, 0.488, 0.523, all P<0.01). Regression analysis showed that resilience could positively predict PTG ( β=0.518, P<0.01). Psychological resilience positively predicted hope ( β=0.188, P<0.01). Resilience ( β=0.204, P =0.002) and hope ( β=1.442, P<0.01) could positively predict PTG. Hope played a partial mediating role in the relationship between resilience and PTG, and the mediating effect accounted for 60.23%. Conclusions:rSHPT patients generally had lower levels of hope, resilience and PTG. Resilience can affect PTG directly or indirectly through hope. Medical staff should improve the resilience and hope level of patients with rSHPT through positive psychological intervention measures, so as to enhance the positive promoting effect of psychological resilience on PTG.
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Autism spectrum disorder(ASD)is a neurodevelopmental disorder which pathogenesis has not been determined.At present, rehabilitation behavior intervention and education are the main treatments.Various animal models and clinical trials have shown that its pathogenesis is related to the regulatory changes of some molecular pathways.At present, there are many signaling pathways reported in the literature such as mTOR, Wnt/β-catenin, Notch, Reelin, JAK-STAT, Sonic hedgehog, IQSEC2 and so on.This article reviews the related researches on a wider range of signaling pathways and the pathogenesis of ASD, and describes the abnormalities in molecular pathways of ASD, which will be helpful for the study of ASD.
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Objective: To investigate the distribution characteristics of LymphGen genotyping in a diffuse large B-cell lymphoma (DLBCL) population and verify its prognostic value. Methods: We collected the clinical data and paraffin-embedded tumor tissue samples of 155 patients with newly diagnosed DLBCL in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. DNA was extracted from tumor tissue and 475 gene mutations were detected by next-generation sequencing technology. We investigated the distribution of LymphGen genotyping in the DLBCL population, patients with different COO genotypes in the Xinjiang region, and their effects on PFS and OS. Results: ①Among 155 patients, 105 patients (67.7%) could be genotyped, including 14 (9.0%) for MCD, 26 (16.8%) for BN2, 10 (6.5%) for N1, 8 (5.2%) for EZB, 27 (17.4%) for A53, and 20 (12.9%) for ST2. ②The distribution of each gene subtype was different in different cell origin (COO) types (P=0.021) . ST2 was dominant in the germinal center type (GCB) group (28.8%) , and A53 and MCD were dominant in the non-GCB group (35.8%, 17.0%) . The BN2 type was the most common in both groups (23.1%, 26.4%) . ③There were statistically significant differences in progression-free survival (PFS) and overall survival (OS) among different gene subtypes (P=0.031 and 0.005, respectively) . N1 and A53 had poor prognosis. The 2-year PFS and OS rates of N1 were both (21.3±18.4) %, and the 3-year PFS and OS rates of A53 were (60.9±11.3) %, (46.8±10.9) %, respectively. ④ The 3-year PFS and OS rates of MCD were the best, but the 5-year PFS and OS rates were worse. ⑤In the ROC curve of LymphGen genotyping for OS prediction, the AUC was 0.66, showing a certain degree of differentiation. Conclusion: LymphGen genotyping in the DLBCL population was different from previous reports and was of great significance for the prognosis of patients with DLBCL.
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Antineoplastic Combined Chemotherapy Protocols , Disease-Free Survival , Genotype , Humans , Interleukin-1 Receptor-Like 1 Protein , Lymphoma, Large B-Cell, Diffuse/drug therapy , Prognosis , Retrospective StudiesABSTRACT
Objective:To observe any effect of body-weight-supported treadmill training (BWSTT) combined with functional electrical stimulation (FES) on lower limb motor function and the walking ability of hemiplegic stroke survivors.Methods:Fifty-eight stroke survivors with hemiplegia were randomly divided into an FES group of 19, a BWSTT group of 19 and a combination group of 20. In addition to their early routine rehabilitation therapy, the FES and BWSTT groups were provided with the respective therapies, while the combination group received both. The three groups received 30 minutes of treatment a day, 5 days a week for 8 weeks. The Berg Balance Scale (BBS), the simplified version of the Fugl-Meyer assessment scale for the lower extremities (FMA-LE), the 10-metre walk test (10MWT) and functional ambulation classification (FAC) were used to evaluate the subjects′ balance, lower-limb motor function, walking speed and walking function before and after the 8 weeks of treatment.Results:After the treatment, the average BBS, FMA-LE, 10MWT and FAC scores of all three groups had improved significantly, but the combination group′s averages were then significantly better than those of the other two groups.Conclusions:BWSTT combined with FES can best improve the balance, lower-limb motor functioning and walking of hemiplegic stroke survivors.
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Objective:To evaluate clinical efficacy and safety of calcium-based antimicrobial peptide compounds cooling gel (CAPCS cooling gel) in the treatment of atopic dermatitis (AD) .Methods:A randomized, double-blind, active-controlled clinical study was conducted. From July 2019 to May 2020, 80 adult patients with mild-to-moderate AD were enrolled from Beijing Friendship Hospital, Capital Medical University, and randomly and equally divided into 2 groups: test group topically treated with CAPCS cooling gel, control group topically treated with hydrocortisone cream, and the treatment was performed thrice a day for 4 consecutive weeks. Before, 1, 2 and 4 weeks after the start of treatment, efficacy was evaluated according to the Eczema Area and Severity Index (EASI), Visual Analog Scale (VAS), and Investigator′s Global Assessment (IGA) scores, and adverse events were recorded. Efficacy and safety were compared by using repeated measures analysis of variance and chi-square test.Results:Of the 80 patients with AD, 43 were males and 37 were females, and the age was 52.71 ± 16.71 years. Before the treatment, there was no significant difference in gender, age, EASI, VAS or IGA scores between the two groups (all P > 0.05). After 1- and 2-week treatment, there was no significant difference in the response rate between the test group (10.00% [4/40], 57.50% [23/40], respectively) and control group (15.00% [6/40], 52.50% [21/40] respectively, both P > 0.05). After 4-week treatment, the response rate was significantly higher in the test group (82.50%, 33/40) than in the control group (57.50%, 23/40, P < 0.05). Compared with the control group, the test group showed significantly decreased VAS scores after 1-, 2- and 4-week treatment ( U = 1253.00, 1121.00, 1091.50, respectively, all P < 0.05). No drug-related adverse events were observed in either of the groups. Conclusion:CAPCS cooling gel is safe and effective in the treatment of mild-to-moderate AD in adults, and can be applied in clinic.
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Objective:To screen small-molecule inhibitors of tyrosine kinase receptor B2 (EphB2) by using a molecular docking method, and to investigate their effect on cutaneous squamous cell carcinoma (CSCC) and possible mechanisms of action.Methods:The three-dimensional structure of EphB2 protein and its ligand binding sites were predicted by using the docking tool Schrodinger, and high-throughput virtual screening of EphB2 inhibitors was carried out by molecular docking. The anti-CSCC effect and mechanism of action of the screened EphB2 inhibitors kaempferitrin and aloe-emodin (AE) were verified in in vitro and in vivo experiments. In the in vitro experiments, human CSCC cell lines A431 and SCL-1, as well as the human immortalized keratinocyte HaCaT, were all divided into blank control group, dimethyl sulfoxide (DMSO) group, AE group and kaempferitrin group. Methyl thiazol tetrazolium (MTT) assay (AE at concentrations of 20, 40, 80, 160 μmol/L, kaempferitrin at concentrations of 12.5, 25, 50, 100 μmol/L), scratch and Transwell assays (AE at a fixed concentration of 80 μmol/L, kaempferitrin at a fixed concentration of 50 μmol/L) were performed to analyze the effect of EphB2 inhibitors on the proliferation, migration and invasion of CSCC cells. In the in vivo experiments, specific pathogen-free BALB/c female nude mice were subcutaneously injected with 0.2 ml of A431 cell suspension. After tumor growth, 24 tumor-bearing mice were randomly and equally divided into 4 groups: AE group and kaempferitrin group intraperitoneally injected with 20 mg·kg -1·d -1 AE and 25 mg·kg -1·d -1 kaempferitrin respectively, blank control group and DMSO group intraperitoneally injected with the same volume of sodium chloride physiological solution and DMSO respectively; the tumor size and body weight of nude mice were measured weekly; after consecutive treatment for 28 days, transplanted tumors were resected from the nude mice for hematoxylin and eosin (HE) staining, and real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis were performed to analyze the effect of AE and kaempferitrin on the mRNA and protein expression of E-cadherin, vimentin, glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β (p-GSK-3β) and β-catenin respectively. One-way analysis of variance and t test were used for comparisons between groups. Results:Two small-molecule compounds AA-504/20999031 (kaempferitrin) and AA-466/21162055 (AE) with high inhibitory activity against EphB2 were screened out. MTT assay showed that both AE and kaempferitrin exhibited strong cytotoxicity to SCL-1 and A431 cells compared with HaCaT cells, and their toxicity increased with the increase of their concentration ( F = 17.95, 11.34, respectively, both P < 0.001) ; after 48-hour treatment, the 50% inhibitory concentrations (IC50s) of AE against SCL-1 and A431 cells were 124.59 and 80.85 μmol/L respectively, and the IC50s of kaempferitrin against SCL-1 and A431 cells were 119.64 and 64.96 μmol/L respectively. Scratch assay showed that the migration distance of A431 cells was significantly shorter in the AE group and kaempferitrin group (36.7 ± 1.0 μm, 44.7 ± 3.5 μm, respectively) than in the DMSO group (88.1 ± 1.4 μm, F = 52.34, P < 0.001), while there was no significant difference in the migration distance of HaCaT cells among the above groups ( F = 1.73, P = 0.238). Transwell assay showed that the number of A431 cells crossing the Transwell membrane significantly decreased in the AE group and kaempferitrin group (145.0 ± 2.5, 94.7 ± 4.1, respectively) compared with the DMSO group (195.3 ± 5.7, F = 72.85, P < 0.001), while neither AE nor kaempferitrin showed significant inhibitory effects of on the number of HaCaT cells crossing the Transwell membrane ( F = 3.91, P = 0.055). The animal experiment revealed significantly decreased volumes of transplanted tumors in nude mice in the AE group and kaempferitrin group (407.42 ± 70.37 mm 3, 368.77 ± 62.7 mm 3, respectively) compared with the DMSO group (841.88 ± 84.63 mm 3, F = 73.78, P < 0.001). HE staining confirmed that AE and kaempferitrin could improve pathological changes of transplanted tumors. qRT-PCR and Western blot analysis showed that AE and kaempferitrin significantly up-regulated the mRNA and protein expression of E-cadherin and p-GSK-3β in tumor tissues (all P < 0.001), and down-regulated the mRNA and protein expression of vimentin, β-catenin and GSK-3β (all P < 0.001) . Conclusion:The small-molecule inhibitors screened by molecular docking can form a stable complex with EphB2, and inhibit the progression of CSCC by affecting the Wnt/β-catenin pathway-induced epithelial-mesenchymal transition.
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Objective:To evaluate short-term efficacy and safety of fluticasone propionate 0.05% cream alone or in combination with calcipotriol 0.005% ointment in the treatment of mild to moderate plaque psoriasis.Methods:From October 2020 to January 2021, a randomized, open-labeled, self-controlled clinical trial was conducted among 30 patients with mild to moderate plaque psoriasis in Beijing Friendship Hospital. Skin lesions on the extremity of one side were topically treated with calcipotriol 0.005% ointment in the morning and fluticasone propionate 0.05% cream in the evening (combination group) , and lesions on the contralateral extremity were topically treated with fluticasone propionate 0.05% cream twice a day (fluticasone propionate group) . The treatment lasted 4 weeks. Before and 1, 2, 4 weeks after the start of treatment, the patients were followed up, clinical indices including static physician′s global assessment (sPGA) and psoriasis area and severity index (PASI) were evaluated, and adverse events were recorded. Efficacy and safety were evaluated by using repeated measures analysis of variance, multivariate analysis of variance, Mann-Whitney rank sum test and two-independent-sample t test. Results:Before the treatment, there was no significant difference in sPGA or PASI score between the combination group and fluticasone propionate group (both P > 0.05) . After 1-week treatment, the fluticasone propionate group showed significantly decreased sPGA (1.10 ± 0.31 points) and PASI scores (1.05 ± 0.51 points) compared with the combination group (1.73 ± 0.45 points, 1.38 ± 0.69 points, F= 40.74, 4.38, respectively, both P < 0.05) ; after 2- and 4-week treatment, the combination group showed significantly decreased sPGA (0.83 ± 0.46 points, 0.23 ± 0.43 points, respectively) and PASI scores (0.53 ± 0.47 points, 0.23 ± 0.50 points, respectively) compared with the fluticasone propionate group (sPGA: 1.03 ± 0.18 points, 0.97 ± 0.32 points, F= 4.88, 56.14, respectively, both P < 0.05; PASI: 1.03 ± 0.51 points, 0.92 ± 0.54 points, F= 15.20, 26.36, respectively, both P < 0.05) . After 1-week treatment, the infiltration/hypertrophy severity score was significantly lower in the fluticasone propionate group than in the combination group ( U= 165.00, P < 0.05) ; after 2- and 4-week treatment, the erythema and scaling severity scores were significantly lower in the combination group than in the fluticasone propionate group (erythema: U= 540.00, 765.00, respectively, both P < 0.05; scaling: U= 825.00, 795.00, respectively, both P < 0.05) . Conclusion:Fluticasone propionate 0.05% cream alone exhibited a rapid onset of efficacy in the treatment of psoriasis, while fluticasone propionate 0.05% cream combined with calcipotriol 0.005% ointment was more effective after 2- and 4-week treatment, and both regimens showed a favorable safety profile.
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Objective:To investigate clinicopathological features and prognosis of transformed mycosis fungoides (TMF) .Methods:A retrospective analysis was performed on clinicopathological data collected from 24 patients with TMF, as well as on flow cytometry results of 16 peripheral blood samples obtained from 11 of the 24 patients, who visited Hospital of Dermatology, Chinese Academy of Medical Sciences between 2014 and 2020.Results:Among the 24 patients, 11 were males and 13 were females. Their average age at diagnosis of TMF was 50.0 years (range: 18 - 77 years), and patients with early-stage TMF (9 cases) and tumor-stage TMF (15 cases) were aged 44.8 and 52.6 years on average, respectively. The average time interval from diagnosis of MF to large cell transformation was 3.7 years, and 8 patients were diagnosed with TMF at the initial visit. Histopathologically, large cells infiltrated in a diffuse pattern in 20 cases, as well as in a multifocal pattern in 4, and the proportion of large cells in 7 cases was greater than 75%. Immunohistochemically, 18 patients showed positive staining for CD30, and the proportion of CD30-positive large cells was greater than 75% in 9; negative staining for CD30 was observed in 6. Flow cytometry of 16 peripheral blood samples showed the presence of cell subsets expressing clonal T cell receptor (TCR) -vβ in 2 of 4 patients with early-stage TMF and 10 of 12 with tumor-stage TMF, and tumor cells with higher forward scatter than normal lymphocytes were detected in 16 samples. During the follow-up, among the patients with early-stage TMF, 3 progressed to tumor-stage TMF 3.3 years on average after large cell transformation, 1 progressed to erythrodermic MF in stage IIIA, and the other 4 still showed an indolent course; among the patients with tumor-stage TMF, 1 progressed to stage-IV TMF, and 5 died 3.3 (1.5 - 6) years after large cell transformation.Conclusion:Large cell transformation may occur in patients with MF in any stage, some patients have poor prognosis, so close follow-up is needed for patients with TMF.
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ObjectiveTo study the anti-tumor activity and mechanism of Lycopus lucidus polysaccharide （LLP） in vitro. MethodCell counting kit-8 （CCK-8） assay was used to detect the inhibitory effect of LLP （0， 5， 10， 15， 20 g·L-1） on the proliferation of A549 cells at different time points （24，48，72 h）. The migration and invasion abilities of A549 cells were detected by wound healing assay and transwell assay after LLP （10， 20 g·L-1） treatment for 24，48 h. Propidium iodide （PI） single staining was applied to determine the effect of LLP of different concentrations （10，20 g·L-1） on the cell cycle of A549. The apoptosis of A549 cells induced by LLP （10， 20 g·L-1） was detected by Annexin V-FITC/PI kit. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was adopted to measure effect of LLP （10， 20 g·L-1） on gene expression of cysteine aspartate protease-3 （Caspase-3），cysteine aspartate protease-8 （Caspase-8），cysteine aspartate protease-9 （Caspase-9），cyclin-dependent kinase-1 （CDK-1）， and Cyclin B1 in A549 cells. Western blot was used to detect the effect of LLP on protein expression of Caspase-3，Caspase-8，Caspase-9，B-cell lymphoma 2 （Bcl-2）-associated X protein （Bax），CDK-1，cyclin-dependent kinase-4 （CDK-4），cyclin-dependent kinase-6 （CDK-6），Cyclin B1，and Cyclin D1 in A549 cells. ResultCompared with the blank group， the LLP group showed decreased proliferation， migration， and invasion of A549 cells （P<0.05， P<0.01）， increased proportion of G0/G1 phase （P<0.05）， enhanced apoptosis rate （P<0.05， P<0.01）， elevated mRNA expression of Caspase-3，Caspase-8，and Caspase-9 （P<0.05，P<0.01）， reduced mRNA expression of CDK-1 and Cyclin B1 （P<0.05，P<0.01）， up-regulated protein expression of Caspase-3，Caspase-8，Caspase-9， and Bax （P<0.05， P<0.01）， and down-regulated protein expression of Bcl-2， CDK-1， CDK-4， CDK-6， Cyclin B1， and Cyclin D1 （P<0.05， P<0.01）. ConclusionLLP can inhibit the proliferation of A549 cells， block the cell cycle in the G0/G1 phase （also G2/M phase）， and induce cell apoptosis via the mitochondrial apoptosis pathway and death receptor pathway.
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ObjectiveTo investigate the effect of modified Xiaoyaosan on central dopamine transporter （DAT）/protein kinase C （PKC）-dependent signaling pathway in hyperprolactinemia （HPRL） rats. MethodHPRL rat model was established by chronic combined stress combined with intraperitoneal injection of metoclopramide. Ninety-six rats were randomly divided into six groups， namely， the blank group， model group， western medicine （bromocriptine， 0.001 g·kg-1·d-1） group， and high-， medium-， and low-dose （60， 30， 15 g·kg-1·d-1） modified Xiaoyaosan groups. After 14 days of administration， the serum prolactin （PRL） content was detected by enzyme-linked immunosorbent assay， the expression of tyrosine hydroxylase （TH） in rat hypothalamus by immunohistochemistry， and the protein expression of DAT and PKC in hypothalamus by Western blot. ResultCompared with the blank group， the model group exhibited significantly increased PRL and DAT （P<0.01）， but decreased TH and PKC （P<0.01）. Compared with the model group， bromocriptine and modified Xiaoyaosan at the medium dose significantly lowered the content of PRL （P<0.01）. The modified Xiaoyaosan at the medium and high doses elevated the expression of TH （P<0.05， P<0.01）. The expression levels of PKC in the medium- and low-dose modified Xiaoyaosan groups and the western medicine group were significantly increased （P<0.01）， while the DAT expression levels in the high-， medium-， and low-dose modified Xiaoyaosan groups and the western medicine group were decreased （P<0.01）. ConclusionThe modified Xiaoyaosan is able to up-regulate the expression of TH and down-regulate the level of DAT through PKC-dependent signaling pathway， thereby regulating the PRL.
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ObjectiveTo investigate the effects of micro-fertilizer containing rare earth of different types and concentrations on the growth，yield and quality of Angelica sinensis. MethodOn the basis of the single-factor randomized block design， the growth and index components of Angelica sinensis were determined with rare earth-containing nitrate and chloride micro-fertilizers of different concentrations as foliar fertilizers. ResultSpraying 0.8 g·mL-1 rare earth-containing chloride micro-fertilizer could increase the economic yield of A. sinensis， with the fresh yield per mu （1 mu≈667 m2） reaching 855.4 kg and the dry yield per mu 350.7 kg，which increased by 15.16% and 28.70% respectively compared with that in the control group CK1. Spraying 1.2 g·mL-1 rare earth-containing nitrate micro-fertilizer could promote the growth and development of A. sinensis and significantly increase the content of index components， with the plant height reaching 93.05 cm，the stem diameter 15.60 mm，the root diameter 16.10 mm，the main root length 36.5 cm，and the number of leaves 11.25 pieces per plant， which increased by 32.76%，31.98%，41.98%，53.36%，and 45.16%， respectively， compared with those in the control group CK2. Besides， the content of ferulic acid，volatile oil，ligustilide， and extract was 0.96%，0.41%，0.30% and 48.76%，respectively，which increased by 12.94%，17.14%，11.11%， and 12.07%，respectively，compared with that in the control group CK2. ConclusionSpraying 0.8 g·mL-1 rare earth-containing chloride micro-fertilizer and 1.2 g·mL-1 rare earth-containing nitrate micro-fertilizer can promote the growth and development of A. sinensis，improve the medicinal properties，and increase yield and quality. Rare earth-containing micro-fertilizers can be applied in the standardization of A. sinensis cultivation， which can change the production status of A. sinensis that depends on chemical fertilizers and single fertilization， and promote the green， organic and ecological cultivation of A. sinensis.