AIM: To analyze the clinical outcomes of cyclosporine combined with lacrimal plug in the treatment of dry eye in patients with primary Sjögren's syndrome.METHODS: The clinical data of 60 patients(120 eyes)who were admitted to the ophthalmology department and rheumatology and immunology department of Baoding No.1 Central Hospital and were diagonosed with siogren's syndrome dry eye after multidisciplinary consultation from June 2022 to September 2023 were retrospectively analyzed. All the patients received regular treatment of primary Sjögren's syndrome, and they were divided into three groups according to treatment methods: A, B and C, with 20 cases(40 eyes)in each group. The group A received 0.3% sodium hyaluronate eyedrops, the group B received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops, and the group C received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops combined with binocular lacrimal plugs. The ocular surface disease index(OSDI)score, conjunctival hyperemia score, tear film breakup time(BUT), tear meniscus height(TMH), corneal fluorescein staining(FL)score and tear secretion of the three groups of patients were compared before and at 4, 8 and 12 wk after treatment. The contents of inflammatory factors such as interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in tears were detected before and at 12 wk after treatment.RESULTS: At 4, 8 and 12 wk after treatment, the scores of OSDI, conjunctival hyperemia score and FL in the three groups of patients were lower than those before treatment, and the BUT, TMH and tear secretion were higher than those before treatment(all P<0.001). The OSDI score of the group C was lower than that of the group A and B, and the group B was lower than the group A(all P<0.001). The BUT, TMH and tear secretion of the group C were higher than those of the group A and B, with the group B higher than the group A(all P<0.001). At 12 wk after treatment, the levels of IL-6, TNF-α and IL-1β in the tears of the three groups of patients were lower than those before treatment, with the group C lower than the group A and B, and the group B lower than the group A(all P<0.001). There was no statistical significant difference in the incidence of adverse reactions among the three groups of patients(P>0.05).CONCLUSION: The combined use of cyclosporine and lacrimal plug is safe and effective in improving the clinical symptoms of patients with moderate and severe dry eye, promoting the function of tear film and cornea, increasing tears secretion, and reducing the level of tear inflammatory factors.

AIM: To evaluate the efficacy of 0.05% cyclosporine eye drops in promoting ocular surface recovery following pterygium excision combined with autologous corneal limbal stem cell transplantation.METHODS:This study is a prospective randomized controlled trial, selecting 104 cases(104 eyes)of primary pterygium with monocular onset admitted to Baoding First Central Hospital from September 2023 to September 2024 as the initial sample. The patients were divided into an experimental group and a control group using a random number table method, with 52 eyes in each group. Both groups underwent pterygium excision and autologous corneal limbal stem cell transplantation performed by the same surgeon. The control group received tobramycin dexamethasone eye drops combined with 0.3% sodium hyaluronate eye drops, while the experimental group was additionally treated with 0.05% cyclosporine eye drops. The corneal epithelial repair status, ocular surface function [corneal fluorescein staining(FL)score, Schirmer I test(SIt), break-up time of tear film(BUT)] at preoperative and postoperative time points(1 and 3 mo), and dry eye symptoms [ocular surface disease index(OSDI), standard patient evaluation of eye dryness(SPEED)scores]. Additionally, the recurrence rate and postoperative complications were recorded.RESULTS: During the follow-up period, there was 1 case of loss to follow-up in both the experimental group and the control group, with lost to follow-up rate of 1.9%. Finally, 51 cases in each group completed all followed-up. No statistically significant difference was observed in preoperative general characteristics of patients between the two groups(P>0.05), and there was no statistically significant difference in corneal epithelial repair time or suture removal time(all P>0.05). At 1 mo postoperatively, the SIt and BUT decreased in both groups compared to preoperative levels, with the experimental group showing higher values than the control group(all P<0.05). FL scores increased compared to preoperative levels but were lower in the experimental group(all P<0.05). By 3 mo, the SIt, BUT and FL score of the control group were not statistically different from preoperative levels(all P>0.05), whereas the experimental group showed increased SIt and BUT, which were higher than the control group, and reduced FL scores, and decreased FL scores, which was lower than the control group(all P<0.05). At 3 mo postoperatively, both groups showed increased SIt and BUT compared to 1-month values, with the experimental group outperforming the control group(all P<0.05). FL scores decreased in both groups compared to 1-month values, with the experimental group maintaining lower scores(P<0.05). At 1 mo postoperatively, OSDI and SPEED scores were higher than preoperative levels, with the experimental group higher than the control group(all P<0.05); at 3 mo postoperatively, the scores returned to preoperative level(all P>0.05), and the OSDI and SPEED scores of the control group increased and higher than those of the experiment group(all P<0.05); at 3 mo postoperatively, the OSDI and SPEED scores decreased when compared with 1-month preoperative level, and the experiment group was lower than the control group(all P<0.05). There was no difference in the total incidence of postoperative complications between the two groups(P>0.05). According to the statistics of 6 mo follow-up after operation, there was no recurrence in the experimental group, and the recurrence rate was 11.8% in the control group(P<0.05).CONCLUSION: Adjunctive use of 0.05% cyclosporine eye drops after pterygium excision with limbal stem cell transplantation enhances ocular surface recovery, reduces dry eye symptoms, and lowers recurrence rates without compromising corneal epithelial healing or safety.

Objective:To explore the application of an automatic slide-dropping instrument in bone marrow chromosomal karyotyping.Methods:The effects of manual and automatic dropping methods under different environmental humidity were retrospectively analyzed, and the repeatability of the automatic dropping method was analyzed.Results:No statistical difference was found between the results of automatic and manual dropping methods under the optimum ambient humidity and high humidity ( P>0.05). At low humidity, there was a statistical difference between the two methods ( P<0.05). With regard to the repeatability, the coefficient of variations of the automatic dropping method for the number of split phases, the rate of good dispersion and the rate of overlap were all lower than those of the manual dropping method. A statistical difference was also found in the number of split phases ( P<0.05) but not in the discrete excellent rate and overlapping rate between the two methods ( P>0.05). Conclusion:Better effect can be obtained by the automatic dropping instrument. It is suggested to gradually replace manual work with machine.

Objective To explore the clinical application value of high frequency ultrasound combined with acoustic radiation force impulse in patients with diabetic sarcopenia(DSA).Methods A total of 196 patients with type 2 diabetes mellitus(T2DM)who were hospitalized in the Endocrinology Department of the First Affiliated Hospital of Longyan City,Fujian Medical University were enrolled in this study from January 2022 to February 2023.All the participants were divided into two groups:simple T2DM group(n=120)and combined DSA group(DSA,n=76)according to the limb skeletal muscle mass index(ASMI).During the same period,40 healthy individuals who underwent physical examination were selected as the normal control(NC)group.The general information and biochemical indicators were analyzed in each group.And the muscle thickness,pinnate angle,muscle bundle length and shear wave velocity of the medial head of the right gastrocnemius muscle were compared among the groups.Results The thickness,feathery angle,muscle bundle length,and shear wave velocity of the medial head muscle of the right gastrocnemius muscle were lower in DSA group than in NC and T2DM groups(P＜0.05).Pearson correlation analysis showed that ASMI was positively correlated with body weight,BMI,TC,albumin,total protein,muscle thickness,feather angle,muscle bundle length,and shear wave velocity(P＜0.05),while negatively correlated with age,FPG and HbA1c(P＜0.05).Binary logistic regression analysis showed that muscle thickness and shear wave velocity are influencing factors for DSA.The analysis of the receiver operating characteristic(ROC)curve of the subjects showed that the area under the ROC curve of muscle thickness and shear wave velocity was 0.826 and 0.877(P＜0.05).The diagnostic thresholds for DSA were 14.1 mm and 1.63 m/s,with sensitivity of 0.953 and 0.903,and specificity of 0.971 and 0.941.Conclusions Ultrasound measurement of the muscle thickness and shear wave velocity of the medial head of the right gastrocnemius muscle can be used to diagnose diabetic sarcopenia.

Humans ; Waldenstrom Macroglobulinemia/genetics* ; East Asian People ; Chromosome Aberrations ; Lymphoma

Objective: To observe the effect of angiotensin ( 1-7) ［Ang( 1-7) ］on the apoptosis and angiogenesis of fibroblasts in the oral submucosal fibrosis ( OSF) ，and to explore the effect preliminarily mechanism． Methods: Fibroblasts were isolated and cultured from human buccal mucosal tissue，the cell morphology was observed by inverted microscope，and the expression of vimentin was detected by immunofluorescence staining ; areca nut extract (ANE) was used to induce human fibroblasts to simulate the in vitro model of fibroblasts in OSF，the experimental groups included control group ( normally cultured cells) ，ANE group ( 100 μg/ ml ANE cultured cells for 48 hours) ，ANE + low-dose Ang( 1-7) group ( 100 μg/ ml ANE + 10－7 mol /L Ang ( 1-7) cultured cells for 48 h) ， ANE + high-dose Ang( 1-7) group ( 100 μg/ ml ANE + 10－5 mol /L Ang( 1-7) cultured cells for 48 h) ，immunofluorescence staining detected the expression of α-smooth muscle actin ( α-SMA) ，ELISA method detected the content of Collagen I and Collagen Ⅲ in the cell culture supernatant，MTT method detected cell proliferation activity， flow cytometry detected cell apoptosis ，the tubule formation experiment detected the vascularization of human umbilical vein endothelial cell(HUVEC) ; After the mRFP-GFP-LC3 virus was transferred to the cells，the level of autophagy was detected by immunofluorescence staining，Western blot detected the expression of autophagy-related protein Beclin-1 and the ratio of LC3-Ⅱ/ LC3-Ⅰ . Results: The isolated and cultured cells were in a long spindle shape，and Vimentin was positively expressed，indicating that fibroblasts were successfully isolated ; Compared with the ANE group，the fluorescence expression of α-SMA protein in ANE low dose Ang( 1-7) group and ANE + high dose Ang( 1-7) group significantly decreased，the contents of Collagen I and Collagen Ⅲ in the culture supernatant were reduced (P＜0．05) ，cell proliferation activity decreased (P＜0．05) ，and cell apoptosis rate increased (P < 0．05) ，the cell culture supernatants of the two groups inhibited the angiogenesis of HUVEC (P＜0．05) ，endophagosomes were reduced (P＜0．05) ，Beclin-1 protein expression was reduced (P ＜0．05) ，and the ratio of LC3- Ⅱ / LC3-Ⅰ was down-regulated (P ＜0．05 ) ; in addition ，the effect of ANE + high-dose Ang ( 1-7 ) group was stronger than that of ANE + low-dose Ang( 1-7) group (P＜0．05) ． Conclusion Ang( 1-7) can inhibit the activation of fibroblasts induced by ANE，promote cell apoptosis，and reduce the angiogenesis of HUVEC，this mechanism may be related to the regulation of cell autophagy.

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders.
Autism Spectrum Disorder/metabolism* ; Cell Movement/genetics* ; Humans ; Interneurons/metabolism* ; Neurodevelopmental Disorders/genetics* ; Neurons/metabolism* ; Rho Guanine Nucleotide Exchange Factors/genetics*

Objective:To screen out the differentially regulated metabolites by the analysis of serum metabolic fingerprints, and to provide potential biomarkers for diagnosis of lung cancer.Methods:A total of 228 subjects were enrolled in Changhai Hospital from January 27, 2021 to June 4, 2021, including 97 newly diagnosed lung cancer patients and 131 healthy individuals. Serum samples were collected from the enrolled cohort according to a standard procedure, and the enrolled cohort was divided into a training set and a completely independent validation set by stratified random sampling. The metabolic fingerprints of serum samples were collected by previously developed nano-assisted laser desorption/ionization mass spectrometry (nano-LDI MS). After age and gender matching of the training set, a diagnostic model based on serum metabolic fingerprints was established by machine learning algorithm, and the classification performance of the model was evaluated by receiver operating characteristic (ROC) curve.Results:Serum metabolic fingerprint for each sample was obtained in 1 minute using a novel nano-LDI MS, with consumption of only 1 μl original serum sample. For the training set, the area under ROC curve (AUC) of the constructed classifier for diagnosis of lung cancer was 0.92 (95% CI 0.87-0.97), with a sensitivity of 89% and specificity of 89%. For the independent validation set, the AUC reached 0.96 (95% CI 0.90-1.00) with a sensitivity of 91% and specificity of 94%, which showed no significant decrease compared to training set. We also identified a biomarker panel of 5 metabolites, demonstrating a unique metabolic fingerprint of lung cancer patients. Conclusion:Serum metabolic fingerprints and machine learning were combined to establish a diagnostic model, which can be used to distinguish between lung cancer patients and healthy controls. This work sheds lights on the rapid metabolic analysis for clinical application towards in vitro diagnosis.

Objective:To investigate the clinical characteristics, diagnosis, treatment and prognosis of acute leukemia (AL) with NUP98-DDX10 fusion gene-positive.Methods:The clinical data of 2 AL patients with NUP98-DDX10 fusion gene-positive who admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences in April 2020 and February 2021, respectively were retrospectively analyzed. Transcriptome gene sequencing was used to detect fusion gene, and the fusion gene fragment was amplified by using reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing was used to clarify sequences. The clinical and experimental indicators characteristics were analyzed and the relevant literatures were reviewed.Results:According to the clinical diagnosis, 1 patient was diagnosed as acute myeloid leukemia M 5 (AML-M 5) and 1 patient was diagnosed as acute leukemia of ambiguous lineage, not otherwise specified (ALAL-NOS). The AML-M 5 patient presented with severe coagulation abnormalities, and fulfilled the diagnostic criteria for diffuse intravascular coagulation (DIC) at the initial visit. Transcriptome sequencing of 2 patients showed NUP98-DDX10 fusion gene- positive. RT-PCR confirmed that sequencing results identified 2 different splice fusion modes: one was NUP98 exon 14 fused with DDX10 exon 7(usually called "type Ⅱ"), the other was NUP98 exon 14 fused with DDX10 exon 13, which was never reported and named as "type Ⅳ". From 1997 to 2018, a total of 16 cases with NUP98-DDX10 related hematologic neoplasms were reported in the literature. A summary analysis of 16 cases added with 2 patients in our center included 13 males and 5 females with median age 31.5 years (0.08-61 years). The median overall survival was 12 months (1-46 months). Conclusions:A novel fusion gene NUP98-DDX10 transcriptome is identified in ALAL-NOS patient. Hematological malignancies with NUP98-DDX10 are very rare. They respond poorly to conventional treatment and require allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve the prognosis.

Objective:To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement.Methods:Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed.Results:①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity ( n=five cases) and no starry sky pattern ( n=6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions:LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity’s pathogenesis, treatment options, and long-term prognosis still need to be explored further.