Detection of germline variants in pancreatic cancer by next-generation sequencing and correlation analysis of clinical factors / 复旦学报（医学版）

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

Correlation between baseline aqueous humor cytokine levels and anti-vascu-lar endothelial growth factor treatment in patients with macular edema sec-ondary to retinal vein obstruction / 眼科新进展

Objective To analyze the effect of baseline cytokines in aqueous humor in predicting the improvement of the central macular thickness(CMT)and best corrected visual acuity(BCVA)of patients with macular edema secondary to retinal vein obstruction(RVO-ME)after anti-vascular endothelial growth factor(VEGF)treatment for 3 months.Meth-ods Totally 30 eyes of 30 patients initially diagnosed with RVO-ME in the Affiliated Eye Hospital of Nanjing Medical Uni-versity from October 2021 to January 2023 were enrolled.Aqueous humor was collected by anterior chamber puncture be-fore the anti-VEGF drug injection.The levels of 11 cytokines in aqueous humor,including VEGF,intercellular adhesion molecule(ICAM)-1,interleukins(ILs)and interferon-γ(IFN-γ),were measured by Luminex xMAP technology.The cor-relation between baseline aqueous humor cytokine levels and CMT,BCVA(logMAR)as well as their changes(difference between baseline and anti-VEGF treatment for 3 months)in RVO-ME patients was analyzed;the correlation between CMT and BCVA(logMAR)was analyzed at baseline and 3 months after anti-VEGF treatment.CMT and BCVA responders were defined as patients with 50％or more reduction in CMT and BCVA(logMAR)from baseline to the third month.A Logistic regression model was used to analyze the relationship between baseline aqueous humor cytokines and RVO-ME patients be-coming CMT or BCVA responders after 3 months of anti-VEGF treatment.Results Compared with baseline,the CMT sig-nificantly decreased and BCVA significantly improved in RVO-ME patients after anti-VEGF treatment for 3 months(both P＜0.001).The CMT was positively correlated with BCVA(logMAR)of RVO-ME patients at baseline and after anti-VEGF treatment for 3 months(P=0.026,0.002).At baseline,the levels of VEGF and IL-8 of RVO-ME patients were positively correlated with CMT(P=0.032,0.035);the levels of IL-6 and IL-8 were positively correlated with BCVA(logMAR)(P=0.018,0.002).The baseline IL-8 level in RVO-ME patients was negatively associated with the change in CMT(P=0.024).Logistic regression analysis showed that elevated baseline ICAM-1 level could increase the risk of RVO-ME patients becom-ing BCVA non-responders after 3 months of anti-VEGF treatment(P=0.023).Conclusion Baseline IL-8 and ICAM-1 may be predictors of CMT and BCVA improvement after anti-VEGF treatment of RVO-ME.

Recent advances in biological therapy of diabetic retinopathy / 眼科新进展

Diabetic retinopathy(DR)is one of the most common fundus vascular diseases and a leading cause of blindness in adults of working age.The occurrence and development of DR involves a variety of pathophysiologic mecha-nisms,including metabolic dysregulation,oxidative stress,inflammation,and neurovascular unit hypofunction.Conven-tional clinical treatments,such as anti-vascular endothelial growth factor drugs and retinal laser photocoagulation,have long treatment cycles and variable outcomes in some patients and sometimes require vitrectomy in the later stages of the disease.With the in-depth research on the molecular level of the pathogenesis of DR,a number of biological therapeutic modalities,such as targeted therapy,gene therapy,immunotherapy and cell therapy,have received more and more atten-tion from researchers.This review summarizes the biologic therapeutic modalities currently available for DR and outlines the benefits and limitations of these approaches with a view to informing researchers.

Corneal stromal lenticule-combined accelerated transepithelial corneal collagen cross-linking for severe keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of corneal stromal lenticule-combined accelerated transepithelial corneal collagen cross-linking(SC-A-TE-CXL)in the treatment of severe keratoconus.METHODS: Prospective before-after self-control study. A total of 10 cases(14 eyes)of severe keratoconus with the thinnest corneal thickness(including epithelium)less than 400 μm were collected from March 2019 to July 2022 at the ophthalmology department of Affiliated Eye Hospital of Nanjing Medical University. Among them, 8 males(12 eyes)and 2 females(2 eyes)were treated with SC-A-TE-CXL. Corneal curvature, uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), the thinnest corneal thickness(TCT), central corneal thickness(CCT), non-contact intraocular pressure, endothelial cell density(ECD)and anterior or posterior elevations at the thinnest point before surgery and at 1, 3, 6 and 12 mo postoperatively were observed and recorded, as well as corneal cross-linking depth at 1 mo postoperatively.RESULTS: UCVA and BCVA at 1, 3, 6, and 12 mo after SC-A-TE-CXL were higher than those preoperatively, but there were no differences(F=0.793, P=0.535; F=0.783, P=0.542). K1, K2, Km and Kmax decreased at each time point postoperatively compared with those preoperatively, but there were no differences(F=0.627, P=0.574; F=1.264, P=0.296; F=0.727, P=0.520; F=1.115, P=0.359). Anterior and posterior elevations at the thinnest point both decreased compared with those preoperatively, but the differences were not statistically significant(F=1.046, P=0.359; F=1.164, P=0.337). The non-contact intraocular pressure at each time point postoperatively was higher than that preoperatively, but the differences were not statistically significant(F=0.814, P=0.522). There were no differences in CCT and TCT at any time points of the follow-ups compared with those preoperatively(F=0.931, P=0.453; F=0.782, P=0.542). There was no difference in ECD at 12 mo postoperatively versus preoperative value(t=1.266, P=0.228). At 1 mo postoperatively, anterior segment optical coherence tomography(AS-OCT)exhibited an increase of density in the anterior stroma, and there was a demarcation line with an average depth of 124.07±25.13 μm.CONCLUSION: SC-A-TE-CXL can be considered as a surgical treatment for severe keratoconus, which can delay the progression of severe keratoconus with high safety. However, the long-term efficacy of this treatment requires further observation.

Pricing Methods and Thoughts for Medical Service Item under the Background of Deepening Medical Service Price Re-form / 中国卫生经济

Medical service price reflects the value and the financial compensation for medical services.The medical service price reform plays an important role in optimizing the allocation of medical resources and transforming the operating mechanism of public hospitals.The pricing of medical services should take many factors into consideration such as the characteristics of medical service,service markets,service costs,supply and demand relationships,medical insurance payment policies,compensation mechanisms,and so on.In response to the current situation of price management methods and price levels for medical service in China,various pricing methods such as cost-based pricing,price-regulation pricing,and demand-oriented pricing should be comprehensively utilized to ex-plore a pricing mechanism that separates medical service value from medical service price,human resource value from material con-sumption value,and build a medical service pricing system that could be coordinated with policy objectives.

Application of continuous renal replacement therapy combined with extracorporeal carbon dioxide removal in children with acute respiratory failure / 中华急诊医学杂志

Objective:To explore the role of continuous renal replacement therapy (CRRT) combined with extracorporeal carbon dioxide removal (ECCO 2R) in the treatment of children with respiratory failure. Methods:The clinical data of 12 children with respiratory failure who were treated with CRRT+ECCO 2R in PICU of Jinan Children's Hospital from July 2020 to August 2022 were collected and analyzed retrospectively. The outcomes and the external pipeline usage of the patients were observed, and the blood gas analysis and ventilator parameters before 1 h and after 1, 6, 12 and 24 h of the treatment were compared by one-way ANOVA with LSD post hoc correction. Results:Six patients successfully withdrew from CRRT+ECCO 2R and mechanical ventilation, three patients were transferred to ECMO treatment. Three cases died after voluntary withdrawal of treatment, and two cases died due to treatment failure. The mortality rate was 41.7%. After continuous treatment of CRRT+ECCO 2R for 15 to 112 h, two cases experienced extracorporeal circuit obstruction. After 1 h of treatment, PaCO 2 decreased from (64.67±24.4) mmHg to (49.42±15.54) mmHg, pH increased from (7.28±0.20) to (7.38±0.11), FiO 2 decreased from (0.85±0.13) to (0.78±0.15), PC decreased from (19.42±4.34) cmH 2O to (17.75±4.00) cmH 2O. After 24 h of treatment, PaCO 2 decreased to (39.2±5.55) mmHg, pH increased to (7.41±0.04), FiO 2 decreased to (0.46±0.11), and PC decreased to (13.8±3.36) cmH 2O, and the differences were statistically significant compared with before treatment ( P < 0.05). Conclusions:The combination of CRRT and ECCO 2R therapy can safely substitute for partial lung ventilation/perfusion function, and play a role in protecting right heart function and improving lung-kidney interaction. It can be considered as an option for extracorporeal respiratory, circulatory, and renal support, and consequently has broad prospects.

Research progress of S1P signaling pathway in eye diseases / 中华实验眼科杂志

Sphingolipid metabolism is widely involved in the functional regulation of different cells, and also plays an important role in ocular tissues.Sphingosine 1-phosphate (S1P) is the end product of sphingolipid metabolism and has been shown to play an important role in the onset and development of eye diseases.S1P signaling pathway is widely expressed in various ocular cells and is involved in the regulation of cell proliferation, differentiation, migration and apoptosis.S1P activates a variety of signaling pathways by binding to corresponding receptors and thus plays a wide range of physiological and pathological effects in the eye.Recent studies have found that the S1P signaling pathway can not only mediate the normal development of blood vessels and nerves in the eye, maintain the normal structure of the ocular tissues, and participate in the metabolism of lipids in the eye, but also has a close relationship with immune-related inflammatory response, pathological fibrosis, destruction of cell functional barrier and other related pathological changes.This paper mainly reviewed the basic overview of the S1P signaling pathway, its physiological role in the eye, and its role in the pathological changes of anterior and posterior segment diseases, so as to provide new directions and targets for the treatment of eye diseases.

Research progress on defocus technique of orthokeratology lens in the prevention and control of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

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.

Expressions of inflammatory factors of aqueous humor before the surgery of chronic primary angle-closure glaucoma and its influence on prognosis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression level of inflammatory factors of aqueous humor before trabeculectomy in binocular chronic primary angle-closure glaucoma(CPACG)and its correlation with postoperative filtration bleb and intraocular pressure.METHODS: A total of 15 cases(30 eyes)with binocular CPACG who admitted to the Affiliated Eye Hospital of Nanjing Medical University from September to December 2021 and received trabeculectomy were selected. The surgery interval between two eyes was 7d, and the preoperative expression levels of monocyte chemoattractant protein-1(MCP-1), interleukin-17(IL-17), transforming growth factor-β(TGF-β), and interferon-γ(IFN-γ)of the aqueous humor in both eyes were respectively detected by enzyme-linked immunosorbent assay(ELISA). Furthermore, the intraocular pressure(IOP)and the morphology of filtering blebs at 1mo after surgery were measured.RESULTS: The concentrations of MCP-1, IL-17, TGF-β, and IFN-γ in aqueous humor from the first eye before surgery were 330.4±46.2, 357.3±46.9, 2347.5±363.8 and 527.7±101.6pg/mL respectively, and those concentrations in aqueous humor from the fellow eye were 298.2±40.7, 309.1±53.5, 1938.3±426.0 and 628.2±104.9pg/mL respectively. The preoperative expression levels of inflammatory factors of aqueous humor in both eyes were statistically significant(P≤0.05). Furthermore, the expression levels of IL-17 and TGF-β in the aqueous humor of patients with CPACG correlated with IOP and the height of filtering blebs at 1mo after surgery(P&#x0026;#x003C;0.05).CONCLUSION: There may be changes in the expression levels of inflammatory factors of aqueous humor in the fellow eye after surgery of the first eye. Moreover, the preoperative expression level of IL-17 and TGF-β in aqueous humor possibly related to postoperative IOP and the height of filtering bleb.

Clinical Characteristics and Prognosis of Children with Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics and prognosis of 40 children with myelodysplastic syndrome (MDS), and provide ideas for clinical diagnosis and treatment.@*METHODS@#The clinical characteristics, risk stratification, and different treatment regimens of 40 cases with MDS admitted in Department of Hematology of Children's Hospital of Soochow University from January 1, 2011 to December 31, 2017 was retrospectively analyzed. Kaplan-Meier survival curve were used to estimate 3-year overall survival (OS) rate and event-free survival (EFS) rate.@*RESULTS@#In 40 cases, the ratio of male to female was 1.4∶1.0, male was more than female, and median age was 6.0 years old. Among them, refractory cytopenia (MDS-RCC) was the most common type, and 11 cases were chromosomal abnormalities, 21 cases genetic abnormalities. Fifteen cases accepted hematopoietic stem cell transplantation (HSCT) treatment, while 25 cases did not but drug therapy alone. The 3-year OS rate of the cases who accepted HSCT or not was (72.2±12.2)% and (35.3±10.2)% (P=0.039), 3-year EFS rate was (65.0±12.9)% and (19.2±8.4)% (P=0.012), respectively. Cox regression analysis showed that age < 7 years old (P=0.0333), initial diagnosed platelet < 50×109/L (P=0.007), presence of complex karyotypes and/or gene mutations (P=0.0002), and treatment without HSCT (P=0.016) were the high-risk factors of prognosis. All the children were classified according to IPSS, WPSS and IPSS-R, while analysis result showed that the above three risk assessment had limitations for risk assessment of MDS in children, they could not comprehensively assess the prognosis of children with MDS.@*CONCLUSION@#MDS-RCC in children is more common. Cox multivariate analysis shows that age < 7 years old, initial diagnosed platelet < 50×109/L, presence of complex karyotypes and/or gene mutation, and treatment without HSCT are the high-risk factors of prognosis in children with MDS. HSCT is the most effective treatment to cure children with MDS at present. The current methods such as IPSS-R commonly used in assessment of prognosis in children with MDS show obvious limitation.

Network pharmacology analysis of ginkgo leaves extract against diabetic retinopathy / 中华实验眼科杂志

Objective:To explore the key targets of ginkgo leaves extract against diabetic retinopathy (DR), and the underlying pharmacological mechanism by network pharmacology.Methods:Potential targets of active components in ginkgo folium were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Swiss Target Prediction database.Therapeutic targets highly related to DR were retrieved from the GeneCards and DisGENET databases.The intersection targets were subjected to Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to construct the active components-targets network.Based on the degree of network nodes, key active components and key targets were obtained for molecular docking verification.Results:A total of 27 active components and 34 potential therapeutic targets of ginkgo leaves extract in the treatment of DR were screened out.GO enrichment analysis indicated that these therapeutic targets were mainly enriched in the processes of inflammation, oxidative stress, angiogenesis and hypoxic damage.KEGG pathway enrichment analysis revealed that the advanced glycation end product-receptor for advanced glycation end product, mitogen active protein kinase, phosphatidylinositol-3-kinase-protein kinase B, hypoxia inducible factor-1, tumor necrosis factor (TNF) and interleukin (IL)-17 signaling pathways were mainly enriched.According to degree value calculated from the active components-targets network, the top 4 key active components with higher degrees were quercetin, kaempferol, luteolin and isorhamnetin, and the top 8 key targets were serine/threonine protein kinase 1, vascular endothelial growth factor A, IL-6, TNF, nitric oxide synthase 3, peroxisome proliferator activated receptor-γ, IL-10 and matrix metalloproteinase-9.The binding activity between key active components and key targets was good.Conclusions:A variety of active compounds contained in ginkgo leaves extract can target various therapeutic targets related to DR, and regulate multiple signal pathways, thereby exerting a therapeutic effect on DR.

Changes of corneal parameters in different areas after cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the distribution characteristics of axial sagittal front power(ASF), true net power(TNP), total corneal refractive power(TCRP)and the difference in back-front corneal radius ratio(B/F ratio)after cataract surgery.METHODS: A prospective study. A total of 156 patients(156 eyes)with age-related cataract who attend Weifang Eye Hospital for cataract surgery from December 2020 to May 2021 were collected. Pentacam was performed before operation and 3mo after operation to collect ASF, TNP and TCRP on 2, 4 and 6mm diameters rings and areas on the corneal apex and pupil-centered, as well as B/F ratio.RESULTS: 3mo after operation, there was no statistical difference in ASF on the 2mm diameters ring and area centered on the corneal apex compared with preoperative values(all P&#x003E;0.05), however, the ASF values on the 4 and 6mm diameters rings and areas were significantly different from those before surgery(all P&#x003C;0.05); There was no statistical difference in ASF on the 2mm diameters rings and areas centered on the pupil compared with preoperative values(all P&#x003E;0.05). The postoperative values of TNP and TCRP on the 2, 4 and 6mm diameters rings and areas centered on the corneal apex and centered on the pupil were statistically different before surgery(all P&#x003C;0.05). Preoperative, TCRP values were different between 2mm and 6mm and between 4mm and 6mm on both corneal apex and pupil-centered rings(all P&#x003C;0.0167), TCRP values were all different between 2mm and 6mm diameters areas on corneal apex and pupil-centered(all P&#x003C;0.0167); 3mo after operation, TCRP values were different on corneal apex and pupil-centered rings between 2mm and 6mm and between 4mm and 6mm diameters(all P&#x003C;0.0167). While TCRP values on the corneal apex and pupil-centered areas were only different between 2mm and 6mm diameters(all P&#x003C;0.0167). The preoperative B/F ratio of patients was 81.79%±1.87%, and the postoperative B/ F ratio of patients was 80.68%±2.23%(P&#x003C;0.001).CONCLUSION: Corneal parameters of different diameters of rings and areas centered on the corneal apex and pupil before and after cataract surgery may change and differ, which should be taken into account when selecting the K value for intraocular lens calculation and individualizing the selection of IOLs based on corneal characteristics.

Analysis of dynamic image features of tear film in dry eye patients / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the image features of dynamic changes of tear film break-up after corneal fluorescein staining(FL)combined with tear film lipid layer(TFLL)dynamic changes in patients with dry eye and its value of diagnosis in dry eye. METHODS: A prospective study. A total of 66 patients(132 eyes)with dry eye admitted to our hospital during September 2019 to December 2020 were divided area break-up group(17 cases, 28 eyes), circle break-up group(20 cases, 27 eyes), line break-up group(25 cases, 28 eyes), spot break-up group(21 cases, 24 eyes)and random break-up group(20 cases, 25 eyes)according to the different fluorescein tear film break-up patterns(BUPs). The image features of tear film break-up dynamic changes and the image features of TFLL dynamic changes were compared in each group, and the differences in the first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tear meniscus height(TMH)and fluorescein staining scores were compare,RESULTS:A statistically significant differences were observed in NIBUTf among the groups of patients(P&#x003C;0.001). Except that there was no difference between spot break-up group and random break-up group(7.56±1.54s vs 8.02±1.86s, P=0.881), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There were statistically differences among the groups for NIBUTav(P&#x003C;0.001). Except that there was no difference between spot break-up group and random break-up group(9.54±2.12s vs 9.73±1.94s, P=0.997), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There was statistically difference among the groups for TMH(P&#x003C;0.001). Except that there was no difference between circle break-up group and line break-up group(0.16±0.03mm vs 0.17±0.03mm, P=0.986), there was no difference between spot break-up group and random break-up group(0.22±0.03mm vs 0.21±0.05mm, P=0.993), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There were statistically significant differences among the groups for FL scores and TFLL grading(P&#x003C;0.001).CONCLUSION:It is shown that different fluorescein BUPs intuitively reflects the tear film structure of the pathological changes according to evaluation and analysis of images feature of dynamic changes of FL tear film and TFLL combined with the results of static examination of tear film. It is helpful for clinicians to identify subtypes of dry eye, which has potential clinical value for the diagnosis and classification of dry eye.

Research on lightweight model of intelligent-assisted diagnosis of common fundus diseases based on fundus color photography / 中华眼底病杂志

Objective:To observe the diagnostic value of six classification intelligent auxiliary diagnosis lightweight model for common fundus diseases based on fundus color photography.Methods:A applied research. A dataset of 2 400 color fundus images from Nanjing Medical University Eye Hospital and Zhejiang Mathematical Medical Society Smart Eye Database was collected, which was desensitized and labeled by a fundus specialist. Of these, 400 each were for diabetic retinopathy, glaucoma, retinal vein occlusion, high myopia, age-related macular degeneration, and normal fundus. The parameters obtained from the classical classification models VGGNet16, ResNet50, DenseNet121 and lightweight classification models MobileNet3, ShuffleNet2, GhostNet trained on the ImageNet dataset were migrated to the six-classified common fundus disease intelligent aid diagnostic model using a migration learning approach during training as initialization parameters for training to obtain the latest model. 1 315 color fundus images of clinical patients were used as the test set. Evaluation metrics included sensitivity, specificity, accuracy, F1-Score and agreement of diagnostic tests (Kappa value); comparison of subject working characteristic curves as well as area under the curve values for different models.Result:Compared with the classical classification model, the storage size and number of parameters of the three lightweight classification models were significantly reduced, with ShuffleNetV2 having an average recognition time per sheet 438.08 ms faster than the classical classification model VGGNet16. All 3 lightweight classification models had Accuracy > 80.0%; Kappa values > 70.0% with significant agreement; sensitivity, specificity, and F1-Score for the diagnosis of normal fundus images were ≥ 98.0%; Macro-F1 was 78.2%, 79.4%, and 81.5%, respectively.Conclusion:The intelligent assisted diagnosis of common fundus diseases based on fundus color photography is a lightweight model with high recognition accuracy and speed; the storage size and number of parameters are significantly reduced compared with the classical classification model.

The influencing factors of cognitive impairment in patients with silicosis / 中华劳动卫生职业病杂志

Objective: To explore the influencing factors of cognitive impairment in patients with silicosis, and to analyze the effect of brain-derived neurotrophic factor (BDNF) on cognitive function. Methods: In March 2021, 484 silicosis patients from April 2018 to April 2020 were included in the study. The Montreal Cognitive Assessment Scale of Chinese version was used to evaluate their cognitive function, and they were divided into the cognitive impairment group (n=282) and the non cognitive impairment group (n=202) , another 30 healthy persons from body check were served as control group. The concentrations of BDNF were compared between the three groups. And the receiver operating characteristic (ROC) curve was drawed to analyze the value of BDNF in predicting cognitive impairment in silicosis patients. And the logistic regression analysis was used to explore the risk factors of cognitive impairment. Results: The incidence of cognitive impairment in silicosis patients was 58.26% (282/484) . The level of BDNF in the cognitive impairment group[ (10.32±2.11) mg/L] was significantly lower than that in the non cognitive impairment group[ (13.43±3.45) mg/L] (t=-12.27, P<0.001) . The results of ROC curve analysis showed that the area unde the curve of BDNF in predicting cognitive impairment of silicosis patients was 0.763 (95%CI: 0.613-0.874, P=0.024) , the cut off value was 10 mg/L, the sensitivity was 0.88, and the specificity was 0.84. Logistic regression analysis showed that the level of BDNF (≤10 mg/L) , age (≥65 years old) , course of disease (≥5 years) and diabetes mellitus were the risk factors of cognitive impairment in silicosis patients (OR=2.346, 95%CI: 1.654-3.103; OR=1.757, 95%CI: 1.214-1.998; OR=1.346, 95%CI: 1.112-1.564; OR=1.165, 95%CI: 1.102-1.542, P=0.001, 0.012, 0.027, 0.036) . Conclusion: BDNF may be one of the indicator to predict the risk of cognitive impairment in patients with silicosis.

Research progress on the role of Müller glial cells in retinal nerve injury / 国际眼科杂志(Guoji Yanke Zazhi)

Müller glial cells(MGCs)are the major type of glial cells in the retina which radiating across the entire retina. MGCs make a close contact with retinal neurons, interact, and contribute to retinal homeostasis. After retinal nerve injury, MGCs respond to retinal injury in a variety of regulatory ways to protect the inner retinal environment changes and damage, producing retinal neuroprotective effects, such as regulating neurotransmitters release, releasing neuroprotective factors and antioxidant factors and reprogramming for endogenous repair. However, persistent pathological stimulation in retina can also exacerbate MGCs' proliferation which participate in neuronal dysfunction or loss. Therefore, a proper understanding of the response of MGCs to pathological stimuli and their protective and damaging effects will have a great impact on revealing mechanisms of retinal nerve damage disease and guiding the treatment of the disease. This article reviews the role of MGCs in retinal nerve injury and repair and provides new strategies for retinal neuroprotection.

Effect of Extracts from Veronica peregrine on Breast Cancer Cell-induced Osteoclastic Bone Metastasis via Inhibiting Runx2 Activation / 中国实验方剂学杂志

ObjectiveTo investigate inhibitory effect of extracts from Veronica peregrina （EVP） on the osteoclastic bone metastasis induced by breast cancer cells. MethodBone metastasis model was established by injection of MDA-MB-231 cells， a human breast cancer cell line， into the left ventricle of BALB/c nude mice. The expression of human cytokeratin-19 （Ck-19） gene in mouse bone marrow was determined by nested polymerase chain reaction（PCR） to assess the bone metastasis of MDA-MB-231 cells. To assess the effects of EVP on the activation of bone marrow macrophages （BMMs）， we counted the multinuclear cells and measured the secretion of Cathepsin K. Western blot was adopted to assess the effects of EVP on receptor activator of nuclear factor-κB （RANK）， Runt-related transcription factor 2 （ Runx2 ）， phosphorylated Runx2 （p-Runx2）， and matrix metalloproteinase-9 （MMP-9） in BMMs. Gelatin zymography was employed to determine the activities of matrix metalloproteinases （MMPs）. ResultCompared with that in the blank group， Ck-19 expression was down-regulated in EVP groups （P<0.05）. The multinucleated cells increased when the BMMs were induced by soluble receptor activator of nuclear factor-κB ligand （sRANKL）， which was inhibited by EVP （P<0.05）. The level of cathepsin K in the supernatant of sRANKL group increased compared with that of the blank group， while EVP groups had lower cathepsin K levels than sRANKL group （P<0.05）. Compared with the blank group， the sRANKL group showed up-regulated RANK expression， Runx2 phosphorylation， and MMP-9 expression （P<0.05）， while the expression levels of RANK， p-Runx2， and MMP-9 were down-regulated when the cells were incubated with EVP （P<0.05）. Furthermore， exposure of BMMs to sRANKL resulted in an increase in gelatin hydrolyzation compared with the blank group （P<0.01）， which， however， was reversed in EVP groups （P<0.05）. ConclusionEVP significantly inhibits bone marrow metastasis of MDA-MB-231 cells， which may be associated with the suppression of osteoclast activation by inhibiting Runx2 phosphorylation.

Clinical Effect of Tyrosine Kinase Inhibitors in the Treatment of P230 Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients.@*METHODS@#The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR.@*RESULTS@#There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months.@*CONCLUSION@#For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.

Regulatory Effect of Volatile Oil from Sishenwan on TLR/MyD88 Signaling Pathway in Mice with Chronic Ulcerative Colitis / 中国实验方剂学杂志

Objective:To explore the underlying mechanism of volatile oil from Sishenwan in treating chronic ulcerative colitis through the Toll-like receptor （TLR）/myeloid differentiation factor 88 （MyD88） signaling pathway. Method:The BALB/c mice were randomly divided into a normal group （normal）， a model group ［dextran sodium sulfate （DSS）］， a Sishenwan volatile oil group， an Ershen pill volatile oil group， a Wuweizi powder volatile oil group， and a mesalazine control group. The chronic ulcerative colitis model was induced by DSS in mice. Seven days after intragastric administration， the efficacy was evaluated based on the body weight， colon weight， colon weight index， colon length， and pathological damage score under colonoscopy. The levels of interleukin （IL）-4， IL-10， IL-17A， IL-21， and interferon-<italic>γ </italic>（IFN-<italic>γ</italic>） in the supernatant of colon tissues were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression levels of proteins related to the TLR/MyD88 signaling pathway in the colon mucosa of mice， including TLR2， MyD88， Ras-related C3 botulinum toxin substrate 1 （Rac1）， IL-1 receptor-associated kinase 4 （IRAK4）， IRAK1， tumor necrosis factor receptor （TNFR）-associated factor 6 （TRAF6）， transforming growth factor-<italic>β</italic>-activated kinase 1 binding protein 1 （TAB1）， TAB2， mitogen-activated protein kinase kinase 6 （MKK6）， p38 mitogen-activated protein kinase （p38 MAPK）， and cyclic adenosine monophosphate response element-binding protein （CREB）. Result:Compared with the normal group， the model group showed decreased colon length， increased colon weight， colon weight index， and pathological damage score under colonoscopy， decreased IL-10 level in the colon tissues， increased IL-4， IL-17A， IL-21， and IFN-<italic>γ</italic> levels （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and up-regulated protein expression of TLR2， MyD88， Rac1， IRAK4， IRAK1， TRAF6， TAB1， TAB2， MKK6， p38MAPK， and CREB （<italic>P<</italic>0.01）. Compared with the model group， the Sishenwan volatile oil group showed increased colon length， reduced colon weight， colon weight index， and pathological damage score under colonoscopy， elevated IL-10 level in the colon tissues， decreased IL-4， IL-17A， IL-21， and IFN-<italic>γ</italic> levels （<italic>P<</italic>0.05， <italic>P<</italic>0.01），and down-regulated protein expression of TLR2， MyD88， Rac1， IRAK4， IRAK1， TRAF6， TAB1， TAB2， MKK6， p38MAPK， and CREB （<italic>P<</italic>0.05， <italic>P<</italic>0.01）. Conclusion:The volatile oil from Sishenwan can effectively improve the inflammatory response of chronic ulcerative colitis， which may be achieved by regulating the TLR/MyD88 signaling pathway.

Danshen Injection Inhibits SKOV3 Cell Proliferation in Vitro by Interfering with Their Interaction with Platelets / 中国实验方剂学杂志

Objective:To investigate the inhibitory effects of Danshen injection against ovarian cancer cell proliferation induced by the interaction between platelets and cancer cells. Method:The induction of platelets on SKOV3 growth <italic>in vitro</italic> and the inhibitory effect of Danshen injection at 12，24，and 48 g·L^-1 were observed by 3-（4，5-Dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide （MTT） and cell colony formation assays. The content of transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） in the platelet-tumor cell interaction system and platelet supernatant and the effect of Danshen injection on TGF-<italic>β</italic>₁secretion were detected by enzyme-linked immunosorbent assay （ELISA）. The influences of tumor cell culture supernatant on platelet aggregation and secretion and the inhibitory effect of Danshen injection were determined by microplate assay and ELISA. The effects of Danshen injection on platelet nuclear factor kappa B （NF-<italic>κ</italic>B） signaling pathway were assayed by Western Blot. Result:Compared with the blank group， the platelet induction group exhibited significantly elevated absorbance at <italic>A</italic>₅₇₀（<italic>P</italic><0.01）， while the absorbance at <italic>A</italic>₅₇₀ in the platelet + Danshen injection group was significantly lower than that in the platelet induction group （<italic>P</italic><0.01）. The comparison with the Danshen injection group revealed that the cell proliferation inhibitory rate in the platelet + Danshen injection group at the same dose was more significant （<italic>P</italic><0.01）. The number of colonies in the platelet induction group was obviously increased in contrast to that in the blank group（<italic>P</italic><0.05）， while the number of colonies in the platelet + Danshen injection group was significantly lower than that in the platelet induction group（<italic>P</italic><0.05，<italic>P</italic><0.01）. As demonstrated by comparison with the blank group， TGF-<italic>β</italic>₁content in the supernatant of the platelet induction group rose remarkably（<italic>P</italic><0.01）， whereas that in the platelet + Danshen injection group declined（<italic>P</italic><0.01）. Compared with the Danshen injection （24 g·L^-1） group， the platelet + Danshen injection group displayed more obvious inhibition（<italic>P</italic><0.01）. Compared with the blank group， Danshen injection significantly reduced the TGF-<italic>β</italic>₁content in platelet supernatant（<italic>P</italic><0.05，<italic>P</italic><0.01）. There was no significant change in the content of TGF-<italic>β</italic>₁in SKOV3 supernatant treated with Danshen injection. The platelet aggregation， thromboxane A₂（TXB₂）， and serotonin （5-HT） secretion in the SKOV3 cell supernatant induction group were significantly increased as compared with those in the blank group （<italic>P</italic><0.01）， while such indexes in the cell supernatant induction + Danshen injection group were obviously decreased （<italic>P</italic><0.01）. Compared with the Danshen injection （24 g·L^-1） group， the cell supernatant induction + Danshen injection group displayed more obvious inhibition at the same dose（<italic>P</italic><0.01）. Compared with the blank group， the platelet induction group exhibited obviously up-regulated phosphorylated TGF-<italic>β</italic>-activated kinase-1 （TAK-1） and NF-<italic>κ</italic>B， but down-regulated phosphorylated inhibitory protein of NF-<italic>κ</italic>B （I<italic>κ</italic>B）（<italic>P</italic><0.01）， which however were significantly reversed in the platelet + Danshen injection group<bold>（</bold><italic>P</italic><0.01）. Conclusion:Danshen injection affect the proliferation of SKOV3 cells by inhibiting their interaction with platelets， which may be related to the inhibited secretion of TGF-<italic>β</italic>₁.