Objective To investigate the biological function and main molecular mechanism of long noncoding RNA RMRP(lncRNA RMRP)in endometrial carcinoma.Methods The specimens of carcinoma tissues and adjacent tissues of 30 patients with endometrial carcinoma who received surgical treatment in our hospital were collected.RT-qPCR was used to detect the expression of lncRNA RMRP in endometrial carcinoma tissues and adjacent tissues,and HESC cells and HEC-1-A cells.The endometrial carcinoma cell line HEC-1-A was cultured in vitro,and the Vector,pcDNA-RMRP,NC-siRNA,RMRP-siRNA,NC mimic,miR-580-3p mimic,pcDNA-RMRP+NC mimic,pcDNA-RMRP+ miR-580-3p mimic,RMRP-siRNA+Vector,RMRP-siRNA+pcDNA-JAK2,NC inhibitor,and miR-580-3p inhibitor were transfected into HEC-1-A cells as the Vector group,the pcDNA-RMRP group,the NC-siRNA group,the RMRP-siRNA group,the NC mimic group,the miR-580-3p mimic group,the pcDNA-RMRP+NC mimic group,the pcDNA-RMRP+miR-580-3p mimic group,the RMRP siRNA+Vector group,the RMRP-siRNA+pcDNA-JAK2 group,the NC inhibitor group,and the miR-580-3p inhibitor group respectively.RT-qPCR was used to detect the expression of lncRNA RMRP and miR-580-3p in cells.CCK-8 was used to detect cell proliferation rate.The apoptosis rate was detected by flow cytometry analysis.Bioinformatics software and dual luciferase reporter gene experiment were used to predict and verify the targeted relationships between miR-580-3p and lncRNA RMRP,as well as miR-580-3p and JAK2.Western blot was used to detect the protein expression of JAK/STAT signaling pathway.Results Compared with adjacent tissues,lncRNA RMRP was highly expressed in endometrial carcinoma tissues(P<0.05).Compared with HESC cells,the expression of lncRNA RMRP in HEC-1-A cells was significantly increased(P<0.05).pcDNA-RMRP significantly promoted cell proliferation and inhibited cell apoptosis,while RMRP-siRNA significantly inhibited cell proliferation and promoted cell apoptosis,with statistically significant diferences(P<0.05).miR-580-3p was the downstream target miRNA of lncRNA RMRP,and lncRNA RMRP could negatively regulate the expression of miR-580-3p.JAK2 was the downstream target gene of miR-580-3p,and miR-580-3p could negatively regulate the expression of JAK2 protein.pcDNA-RMRP significantly increased the protein levels of JAK2,p-JAK2 and p-STAT3 in the cells,while co-transfection of pcDNA-RMRP and miR-580-3p mimic significantly decreased the protein levels of JAK2,p-JAK2 and p-STAT3,with statistically significant diferences(P<0.05).RMRP-siRNA could signifi-cantly reduce the protein levels of JAK2,p-JAK2 and p-STAT3 in cells.After co-transfection of RMRP-siRNA and pcDNA-JAK2,the protein levels of JAK2,p-JAK2 and p-STAT3 were significantly increased,with statistically significant diferences(P<0.05).In addition,co-transfection of RMRP-siRNA and pcDNA-JAK2 increased cell proliferation and decreased cell apoptosis,with statistically significant diferences(P<0.05).Conclusion Knockdown of lncRNA RMRP could inhibit endometrial carcinoma cell proliferation and promote cell apoptosis by regulating JAK2/STAT3 signaling pathway,which might be a potential therapeutic target for endometrial carcinoma.

Allergen component-resolved diagnosis (CRD) is an emerging molecular diagnostic technology, which can further clarify the protein profile of allergen components in allergic patients, achieve accurate detection of allergens, and have great significance and value for the precise prevention and treatment of allergic diseases. In this article, the CRD technology and its research progress in respiratory allergic diseases are introduced, and the importance of CRD in the evaluation, prevention and treatment of respiratory allergic diseases are discussed.
Humans ; Allergens ; Hypersensitivity ; Respiratory Tract Diseases

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Humans ; Kounis Syndrome/complications* ; Takotsubo Cardiomyopathy/complications*

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

AIM: To investigate the effect of modified Chufeng Yisun Decoction on ocular surface inflammation after pterygium surgery.METHODS: A total of 60 patients(60 eyes)with primary pterygium who underwent pterygium surgery were randomly divided into control group and study group, with 30 cases(30 eyes)in each group. In the control group, patients were treated with pranoprofen eye drops, tobramycin dexamethasone eye drops, and deproteinized calf blood extract eye gel after the surgery. In the study group, patients were treated by oral modified Chufeng Yisun Decoction in addition to the treatments in the control group. The changes of ocular irritation symptoms, ocular inflammatory signs, tear interleukin 6(IL-6)levels, and tear ferning test(TFT)of patients in the two groups were assessed.RESULTS: The visual analogue scale(VAS)in patients of both groups was significantly lower at 2d and 1wk after the surgery than that at 1d after the surgery(all P<0.01), and the VAS of the study group was significantly better than that of the control group at 2d and 1wk after surgery(P<0.01). The ocular signs integrals(OSI)and TFT results of both groups at 1wk were significantly lower than those at 1d after the surgery(all P<0.01), and the OSI and TFT were also lower in the study group than in the control group at 1wk after the surgery(all P<0.01). In addition, the concentration of tear IL-6 in both groups was significantly lower at 1wk after the surgery than 1d after the surgery(all P<0.01), and it was also significantly lower in the study group than in the control group at 1wk after the surgery(P<0.05).CONCLUSION: The combination of Chufeng Yisun Decoction and conventional treatment of western has a better effect on controlling ocular surface inflammation after pterygium surgery.

Allergen component-resolved diagnosis (CRD) is an emerging molecular diagnostic technology, which can further clarify the protein profile of allergen components in allergic patients, achieve accurate detection of allergens, and have great significance and value for the precise prevention and treatment of allergic diseases. In this article, the CRD technology and its research progress in respiratory allergic diseases are introduced, and the importance of CRD in the evaluation, prevention and treatment of respiratory allergic diseases are discussed.
Humans ; Allergens ; Hypersensitivity ; Respiratory Tract Diseases

ObjectiveTo study the conceptual framework and methodological system of the International Classification of Functioning, Disability and Health (ICF) in occupational therapy and its systematic implementation in clinical practice. MethodsBased on the ICF theory and the policy documents of the World Federation of Occupational Therapists, the conceptual framework of occupational therapy and the systematic implementation in clinical settings based on the ICF framework were analyzed. ResultsThis study constructed a conceptual framework and approach for occupational therapy based on ICF, and clarified the goals, principles, and implementation methods of integrated occupational therapy interventions in rehabilitation services. The goal of occupational therapy interventions was to improve the individual activity and participation through multidisciplinary and cross-cutting implementation of integrated occupational therapy programs to optimize functioning. Occupational therapy was based on the bio-psycho-social model, adhered to the principles of person-centeredness and functioning orientation, and implemented individualized intervention programs in different context. In clinical practice, it was recommended to follow ICF-based standardized process and systematically use World Health Organization Family International Classifications: functioning and unmet needs analysis using ICHI; functional classification, assessment and coding using ICF; disease classification, diagnosis and coding using ICD; intervention of occupational therapies using ICHI to build a systematic occupational therapy service system. ConclusionAn ICF-based occupational therapy concept and methodological system has been built, a comprehensive clinical occupational therapy implementation model has been established, the goal of activity and participation oriented occupational therapy interventions has been clarified, and the systematic, structured, standardized and refined level of occupational therapy has been enhanced.

Objective:To investigate the significance of multicolor flow cytometry (MFC) monitoring of minimal residual disease (MRD) in the course of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CD19-chimeric antigen receptor(CAR)-T cell immunotherapy for patients with refractory, relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL).Methods:37 patients with r/r B-ALL admitted to Hebei Yanda Lu Daopei Hospital from January to July 2019, aged 15 (6, 19) years old, including 24 males and 13 females, were treated with CD19-CAR-T cell immunotherapy bridging allo-HSCT. MFC with cytoplasmic CD79a antibody to set up B-cell gates was used to monitor patients′ bone marrow (BM), cerebrospinal fluid (CSF), and tissue samples on day 0 (prior to the CAR-T cell immunotherapy), day 15, day 28 post CAR-T cell immunotherapy, and post transplantation.The MRD values of these samples were analyzed to evaluate the residual tumor cells and metastasis. The killing effect of the CAR-T cells was evaluated by the recovery of CD19+B cells before transplantation and the period between the timepoint when CD19+B cells was recovered and the timepoint when CAR-T cells were infused. Peripheral blood CAR-T cells were counted at different time points. Statistic analysis was performed by Kaplan-Meie assay and Log-rank test to analyze the difference of univariate cumulative survival.Results:(1)Among the 37 patients, 8 died and 29 survived. 5 patients relapsed after transplantation, of which 4 relapsed patients died and 1 survived. (2)MFC MRD negative remission rate of the death group was lower than that of the survival group at the following time points: post-CAR-T therapy and prior to transplantation (5/8 vs. 28/29, χ 2=7.540, P=0.006); day 15 of the CAR-T cell reinfusion (3/8 vs. 24/29, χ 2=6.512, P=0.011); day 28 of the reinfusion (3/8 vs. 276/29, χ 2=10.065, P=0.002). The probability of extramedullary MFC MRD positive tumor infiltration in the death group was higher than that in the survival group(7/8 vs. 14/29, χ 2=3.931, P=0.047). After CAR-T cell immunotherapy, the recovery period of CD19-positive cells in the death group, or the time for CAR-T cells to kill CD19-positive cells, was shorter than that in the survival group [42.00 days(30.00,49.00) vs. 55.00 days(41.50,73.50), Z=0.022, P=0.020]. Conclusion:The positive results of MRD by MFC at the following timepoints may predict unfavorable outcomes, such as post-CAR-T therapy and prior to transplantation, day 15 and 28 of the CAR-T cell immunotherapy, which may provide some guidance for clinical management.

In this study, we investigated the pharmacological effect and possible molecular mechanism of higenamine (HG) in isoproterenol (ISO)-induced myocardial infarction (MI). All procedures were approved by the Institutional Animal Care and Use Committee of the Guangzhou University of Chinese Medicine. ISO was used to induce MI model in rats and H9c2 cells. The effects of HG on biomarkers and cardiac function in MI rats were evaluated by enzyme linked immunosorbent assay (ELISA), echocardiography and hematoxylin-eosin staining (HE). The expression of apoptosis and autophagy related proteins were detected by Western blot in myocardial tissue and H9c2 cells, as well as methyltransferase-like 3 (METTL3) and transcription factor EB (TFEB) protein expression. Molecular docking was used to evaluate the interaction between HG and METTL3. The results showed that HG significantly improved cardiac function and pathologic changes in ISO-induced MI, and inhibited the levels of MI-related biomarkers such as creatine kinase Mb (CK-MB), creatine kinase (CK) and lactate dehydrogenase (LDH). Mechanism studies showed that HG inhibited the expression of apoptosis-related proteins (Bax/Bcl2, caspase3, cleaved-caspase3). Interestingly, HG up-regulated the expression of autophagy related protein Beclin1, promoted autophagy flux, and decreased the ratio of light chain 3B-I/light chain 3B-II (LC-3B-I/LC-3B-II). Further studies found that HG increased the autophagy regulator TFEB and inhibited METTL3 expression. Molecular docking results showed that HG had a good interaction with METTL3. Taken together, HG has a potential anti-MI effect via regulating METTL3/TFEB signaling pathway-mediated autophagy.