Exosomes are commonly found in blood, urine, saliva, ascites, amniotic fluid and other body fluids, and are involved in intercellular communication, signal transduction, transport of genetic material, maintenance of internal environmental homeostasis and immune regulation, with a wide range of important biological functions. Exosomes transport proteins, lipids, and nucleic acids to target cells and facilitate intercellular communication.As research continues, they have been found to play important roles in physiological and pathological processes, and are important biomarkers for the diagnosis and treatment of diseases. It plays an important role in immunomodulation, inflammatory response, and angiogenesis in many diseases such as cancer, cardiovascular diseases, and brain diseases. More researches suggest that exosomes also play an important role in the development and progression of ophthalmic diseases. In this review, the research history and biological functions of exosomes, as well as their pathogenesis and prospects for the application in ophthalmic diseases, including corneal diseases, glaucoma, ocular trauma, age-related macular degeneration, uveitis and intraocular tumors, were discussed

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To systematically evaluate the qualitative study on the sexual health needs of patients with ostomy based on theoretical domains framework (TDF), providing reference for clinical care and practice.Methods:A comprehensive search was conducted for qualitative studies on the sexual experience of ostomy patients in the China National Knowledge Infrastructure, Wanfang Data, VIP database, China Biology Medicine, PubMed, Embase, Web of Science, Cochrane Library, Elton B. Stephens Company (EBSCO), Elsevier Scopus (SCOPUS), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, with a timeframe of from the creation of the databases to April 15, 2024. The Joanna Briggs Institute Evidence Based Healthcare Center Critical Appraisal Tool was used to evaluate the quality of eligible literature, and the theoretical domain framework was used to integrate the extracted results.Results:A total of 11 articles were included and 51 results were extracted. Based on the theoretical framework, map the sexual health needs of ostomy patients to six core areas: knowledge, skills, optimism, outcome beliefs, environment and resources, and emotions.Conclusions:Medical staff should pay attention to the sexual health needs of patients with intestinal stomas. Based on the six core areas of knowledge, skills, optimism, outcome beliefs, environment and resources, and emotions, they should deeply explore the factors that affect their sexual health, provide professional guidance and comprehensive care, and improve their sexual health level and quality of life.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To investigate the effect of tumor necrosis factor-α (TNF-α) on the differentiation of orbital fibroblasts (OF) in thyroid-associated ophthalmopathy (TAO) and its regulation mechanism.Methods:Six patients (six eyes) diagnosed with TAO were collected in Tianjin Medical University Eye Hospital from December 2019 to August 2020.Adipose connective tissue was collected during the orbital decompression surgery.OF was isolated and cultured using the tissue block method and vimentin was identified by immunofluorescence.Lipogenic differentiation of OF was induced and identified by oil red O staining.Complete culture medium containing 0, 0.1, 1.0 and 10.0 μg/L TNF-α was used to induce the dedifferentiation of orbital mature adipocytes.Primary culturing cells, 14-day differentiation cells and 20-day dedifferentiation cells were collected.The relative mRNA expression levels of peroxisomal proliferation-activated receptor (PPARγ), extracellular regulatory protein kinase1 (ERK1), ERK2 and fat-coated protein1 (perilipin1) were detected by real-time fluorescent quantitative PCR.The relative protein expression levels of PPARγ, P-ERK1/2 and perilipin1 were detected by Western blot.Results:Human TAO-derived OF were successfully cultured in vitro, spindle-shaped or polygonal, tightly arranged in a vortex pattern, and immunofluorescence staining for vimentin was positive.After OF adipogenic differentiation, lipid droplet structures could be seen in the cytoplasm of some cells, and the stained lipid droplet structures in the cytoplasm could be seen by oil red O staining, which confirmed that the cells obtained after differentiation were adipocytes.Dedifferentiation of adipocytes was induced by 0.1, 1.0, and 10.0 μg/L TNF-α.With the extension of induction time, the volume of lipid droplets in the cytoplasm and the number of cells containing lipid droplets decreased.Lipid droplets disappeared in the cytoplasm on the 20th day of dedifferentiation, and the cells became long spindle-shaped and tightly arranged, dedifferentiated into fibroblast-like cells.Real-time fluorescence quantitative PCR detection results showed that the relative expression levels of PPARγ, ERK1, ERK2 and perilipin1 mRNA in 14-day differentiation group were 4.26±0.09, 2.01±0.09, 3.23±0.10 and 8.69±0.33, respectively, which were significantly higher than 1.00±0.09, 1.05±0.19, 1.00±0.10 and 1.05±0.07 in primary group, and 1.06±0.03, 1.15±0.11 and 6.27±0.09 in 20-day dedifferentiation group (all at P<0.05). Western blot analysis showed that the expression levels of PPARγ, ERK1/2 and perilipin1 proteins in 14-day differentiation group were 1.07±0.03, 1.00±0.03 and 1.13±0.02, respectively, which were significantly higher than 0.37±0.02, 0.29±0.02 and 0.00±0.00 in primary group, and 0.20±0.02, 0.38±0.06 and 0.00±0.00 in 20-day dedifferentiation group (all at P<0.001). Conclusions:TNF-α has a dedifferentiation effect on TAO orbital adipocytes.The mechanism may be related to the downregulation of ERK1/2-PPARγ-perilipin1 signaling pathway.

Objective:To investigate the effects of sclerostin (SOST) and WNT/CTNNB1 signaling pathway on the cell cycle, migration and invasion of human uveal melanoma (UM) cells and its related mechanism.Methods:UM tissues from 20 cases of epithelioid UM and 16 cases of spindle cell type UM were collected.The contents of SOST, Wnt-1 and Catenin beta-1 proteins in the collected tissues were detected by immunohistochemical staining.Three human UM tissue derived cell lines OCM-1 (primary spindle cell type), Mum-2B (metastatic epithelioid) and Mum-2C (metastatic spindle cell type) were selected and divided into three groups, blank control group not transfected, empty vector group transfected with SOST negative control vector and SOST siRNA group transfected with SOST siRNA.After 24-hour transfection, the mRNA and protein expression levels of SOST, CTNNB1, WNT protein family 1 (WNT1), CCND1, matrix metalloproteinase (MMP)2 and MMP9 were detected by real-time fluorescence quantitative PCR and Western blot, respectively.The invasion and migration ability of the transfected cells were measured by transwell method, and the cell cycle distribution was detected by flow cytometry.Another 9 female BALB/c nude mice were selected and randomized into OCM-1 group, OCM-1 empty vector group and SOST shRNA group, inoculated with OCM-1 without lentivirus infection, OCM-1 with blank lentivirus infection and OCM-1 with SOST shRNA lentivirus infection, respectively.Six weeks after inoculation, the in situ formation of tumor was observed.The interaction between SOST and low density lipoprotein receptor related protein(LRP)-5/6 in OCM-1 cells was explored by co-immunoprecipitation assay.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (2018KY[L]-20).Results:Immunohistochemical staining results showed that the SOST expression level was higher and the expression levels of Wnt-1 and Catenin beta-1 were lower in spindle cell type UM tissues than in epithelioid UM tissues, and the differences were all statistically significant (all at P<0.01). The real-time fluorescence quantitative PCR results showed that the relative expression of SOST mRNA was significantly lower and the relative expressions of CCND1, WNT1 and MMP9 mRNA were significantly higher in SOST siRNA groups than in corresponding empty vector groups in the three cell lines (all at P<0.05). In OCM-1 and Mum-2C cell lines, the relative expressions of CTNNB1 mRNA were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Western blot results showed that the relative expression of SOST protein was significantly lower and the relative expressions of Wnt-1, Catenin beta-1, cyclin-D1, MMP2 and MMP9 proteins were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Transwell assay showed that the cell invasion and migration ability of SOST siRNA group was significantly higher than that of blank control group and empty vector group in the three cell lines (all at P<0.01). Flow cytometry showed that the proportion of G1-phase cells and the G1/S-phase ratio were significantly lower in SOST siRNA group than in blank control groups and empty vector groups (all at P<0.01). The eyeball volume of OCM-1 group, OCM-1 empty vector group and SOST shRNA group was (42.7±4.6), (49.0±22.9) and (135.2±32.7)mm 3, respectively, showing a significant overall difference ( F=19.963, P<0.01). The eyeball volume of SOST shRNA group was larger than that of OCM-1 group and OCM-1 empty vector group, and the differences were statistically significant (both at P<0.05). Co-immunoprecipitation results showed that SOST could interact with LRP-5 and LRP-6 by binding to them, respectively. Conclusions:Silencing SOST can promote the invasion and migration of UM cells, and increase the proportion of UM cells in the division phase.Silencing SOST can promote tumor growth in eyes of nude mice.SOST may play this function by interacting with the membrane receptor LRP-5/LRP-6 and then regulating the WNT/CTNNB1 signal pathway.

Objective:To evaluate the influence of the clinical staging and different risk factors for the prognosis of ocular adnexal lymphoma.Methods:An ambispective cohort study was conducted.Seventy-four patients diagnosed with primary ocular adnexal lymphoma by pathology at Tianjin Medical University Eye Hospital from November 2010 to December 2018 were enrolled.TNM staging was performed according to local tumor extent, lymph node or systemic involvement.Ann Arbor staging was carried out according to lymph node involvement and extranodal extension.The pathological subtype was classified according to World Health Organization classification of lymphoma.The outcome of disease progression or death was analyzed.Kaplan-Meier method was used for univariate survival analysis.Cox proportional hazard model was employed for multivariate survival analysis to predict the risk factors affecting prognosis, hazard ratio ( HR) and 95% confidence interval ( CI) were estimated.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Tianjin Medical University Eye Hospital (No.2021KY[L]-32). Written informed consent was obtained from all patients before entering the cohort. Results:For TNM staging, there were 68 cases in stage

In adult orbital diseases, thyroid associated ophthalmopathy (TAO) is of very high incidence rate, and it can seriously affect patients' appearance, eyesight and binocular visual function and so on, and significantly reduce the patients' quality of life.In addition to the common manifestations such as eyelid retraction, exophthalmos and strabismus, some TAO patients may suffer from obviously increased ocular pressure and even visual field damage, which are often ignored or missed in diagnosis and should be paid more attention to.The pathogenesis of elevated intraocular pressure in TAO is mainly related to the elevated episcleral venous pressure and the extraocular muscles.Because the elevated intraocular pressure resulted from TAO is secondary and its pathogenesis is complex, personalized treatment different from primary glaucoma therapy is needed.In this article, the epidemiology, pathogenesis and therapy of elevated intraocular pressure in TAO including medication, surgery, and radiotherapy were reviewed to provide reference for the clinical diagnosis and treatment for TAO.

【Objective】 To explore and evaluate the application of blood intelligent management platform (scheme) based on the Internet of Things(IoT)in the clinical blood management for hospitals. 【Methods】 Based on radio frequency identification technology (RFID), smart blood refrigerators, IoT blood shipping containers, automated blood bank systems, smart blood management software, etc. were developed and integrated as an IoT blood intelligent management platform (scheme). The blood storage, management software and hardware systems were organically combined, and the blood storage equipment was moved forward to the clinical departments to solve the concerns of clinicians. 【Results】 The in-depth integration of IoT technology, RFID and refrigeration technology has built an RFID-based IoT blood management solution, which integrates blood storage, transfusion, and quality control management, also realizes the entire process of supervision and traceability of clinical blood transfusion. The forward movement of blood bank to the clinical departments and the implementation of electronic cross-matching streamlined and optimized the clinical blood flow. The waiting time of patient′s for blood transfusion was shortened from (40±10) min to less than 2 min. The whole process of cold chain logistics ensured the storage quality of blood products issued, so that the clinical departments can return the untransfused blood and Blood Transfusion Department can reissue it to other hospitals. 【Conclusion】 IoT blood intelligent management based on RFID realizes the intelligent management of clinical blood transfusion and blood information traceability. The forward movement of blood bank to the clinical departments improves the efficiency of clinical blood transfusion, avoids the waste of blood source, and ensures the safety of blood transfusion. It is worth promoting in the whole process of blood transfusion.

Objective:To measure the choroidal thickness (CT) in the macular area of patients with amblyopia in severe congenital ptosis and to compare the thickness with that of severe congenital ptosis without amblyopia.Methods:A cross-sectional study was performed.Total of 83 eyes of 60 severe congenital ptosis patients were enrolled from January to October in the year 2019 in the Shanxi Eye Hospital, including 29 patients 37 eyes with amblyopia and 36 patients 46 eyes without amblyopia.Thirty-seven eyes of 37 normal people were included in the control group.All subjects underwent mydriatic optometry and the spherical equivalent (SE) was calculated.IOL-Master was used to measure the axial length (AL), and EDI-OCT was used to measure the CT in the macular area.The CT was measured at 13 points: directly beneath the fovea (SFCT) and at 1 mm, 2 mm and 3 mm intervals to the nasal, temporal, superior and inferior to the fovea.The points of CT measurements were named according to their positions and distances relative to the fovea, and represented by SFCT, N1, N2, N3, T1, T2, T3, S1, S2, S3, I1, I2, I3 respectively.The SE, absolute astigmatism degree, AL and CT at each point were compared among the groups.The corrected AL covariance analysis was used to compare the CT at different measurement points among the groups.Spearman rank correlation analysis was used to evaluate the correlation between CT and AL or SE, and unitary linear regression analysis was used to evaluate the influence of age on AL in each group.This study was approved by the Ethics Committee of Shanxi Eye Hospital.All the subjects signed informed consent.Results:Compared with the non-amblyopia group and control group, the SE and absolute astigmatism value was larger, and the AL was shorter in the amblyopia group (all at P<0.05). The mean SFCT was (388.85±54.85), (301.48±56.68), and (287.08±61.88)μm in the amblyopia group, non-amblyopia group, and control group, respectively.Except for I3, the CT values of the rest parts in the amblyopia group were greater than those in the non-amblyopia group and the control group (all at P<0.05). Except for S3 and I3, the CT values of the rest parts in the amblyopia group were greater than those in the non-amblyopia group and the control group after adjusting the AL ( P<0.05). In all the three groups, the CT value was high in the subfovea and was thin in the nasal side.The SFCT was negatively correlated with AL (amblyopia group: rs=-0.340, P=0.045; non-amblyopia group: rs=-0.340, P=0.020; control group: rs=-0.463, P<0.001) and positively correlated with SE (amblyopia group: rs=0.350, P=0.039; non-amblyopia group: rs=0.412, P=0.004; control group: rs=0.450, P=0.005) in each group.Age was the influencing factor of AL in the non-amblyopia group and the control group ( β=0.243, 0.225; both at P<0.001). Conclusions:In comparison with severe congenital ptosis without amblyopia, the SE and absolute astigmatism degree are larger, the AL is shorter, and the CT values at most areas are higher in the severe congenital ptosis with amblyopia.CT value may be associated with the development of amblyopia in severe congenital ptosis.