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OBJECTIVE: Although programmed cell death (PCD) and diabetic nephropathy (DN) are intrinsically conneted, the interplay among various PCD forms remains elusive. In this study, We aimed at identifying independently DN-associated PCD pathways and biomarkers relevant to the related pathogenesis. METHODS: We acquired DN-related datasets from the GEO database and identified PCDs independently correlated with DN (DN-PCDs) through single-sample Gene Set Enrichment Analysis (ssGSEA) as well as, univariate and multivariate logistic regression analyses. Subsequently, applying differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Mfuzz cluster analysis, we filtered the DN-PCDs pertinent to DN onset and progression. The convergence of various machine learning techniques ultimately spotlighted hub genes, substantiated through dataset meta-analyses and experimental validations, thereby confirming hub genes and related pathways expression consistencies. RESULTS: We harmonized four DN-related datasets (GSE1009, GSE142025, GSE30528, and GSE30529) post-batch-effect removal for subsequent analyses. Our differential expression analysis yielded 709 differentially expressed genes (DEGs), comprising 446 upregulated and 263 downregulated DEGs. Based on our ssGSEA as well as univariate and multivariate logistic regressions, apoptosis and NETotic cell death were appraised as independent risk factors for DN (Odds Ratio > 1, p < 0.05). Next, we further refined 588 apoptosis- and NETotic cell death-associated genes through WGCNA and Mfuzz analysis, resulting in the identification of 17 DN-PCDs. Integrating protein-protein interaction (PPI) network analyses, network topology, and machine learning, we pinpointed hub genes (e.g., IL33, RPL11, and CX3CR1) as significant DN risk factors with expression corroborating in subsequent meta-analyses and experimental validations. Our GSEA enrichment analysis discerned differential enrichments between DN and control samples within pathways such as IL2/STAT5, IL6/JAK/STAT3, TNF-α via NF-κB, apoptosis, and oxidative phosphorylation, with related proteins such as IL2, IL6, and TNFα, which we subsequently submitted to experimental verification. CONCLUSION: Innovatively stemming from from PCD interactions, in this study, we discerned PCDs with an independent impact on DN: apoptosis and NETotic cell death. We further screened DN evolution- and progression-related biomarkers, i.e. IL33, RPL11, and CX3CR1, all of which we empirically validated. This study not only poroposes a PCD-centric perspective for DN studies but also provides evidence for PCD-mediated immune cell infiltration exploration in DN regulation. Our results could motivate further exploration of DN pathogenesis, such as how the inflammatory microenvironment mediates NETotic cell death in DN regulation, representing a promising direction for future research.
Subject(s)
Apoptosis , Diabetic Nephropathies , Machine Learning , Diabetic Nephropathies/genetics , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Humans , Computational Biology/methods , Gene Regulatory Networks , Protein Interaction MapsABSTRACT
PURPOSE: We aimed to explore the effects of the ciliary sulcus angle (CSA) on accurate prediction of the vault after phakic implantable collamer lens (EVO ICL Model V4c) using the KS formula. METHODS: Patients were classified according to the size of CSA: group A, narrow angle (CSA < 30°); group B, normal angle (CSA = 30-90°); and group C, wide angle (CSA > 90°). Further, differences between the actual vault dimensions at 3 months postoperatively and the preoperatively predicted vault dimensions in the three groups were analyzed. RESULTS: This study included 223 eyes of 223 individuals. In groups A-C, the difference in the preoperative vault dimensions of the three groups predicted with the KS formula was not statistically significant (P = 0.056). The actual vault dimensions at 3 months postoperatively were significantly different between the three groups (P < 0.001). Moreover, the difference between the actual and predicted vaults by the KS formula was statistically significant (P < 0.001). In the 3 months, after surgery, the percentages of patients with a low vault (< 250 µm) were 0%, 3%, and 29% in groups A, B, and C, respectively. Further, the percentages of patients with an ideal vault (250-750 µm) in the postoperative period were 66%, 84%, and 71% in groups A, B, and C, respectively. Finally, the percentages of patients with a high vault (> 750 µm) in the postoperative period were 34%, 13%, and 0% in groups A, B, and C, respectively. Notably, the distribution of the vault among the three groups was statistically significant (P < 0.001). CONCLUSION: The size of CSA significantly affects the predictiveness of the vault by the KS formula, with the most pronounced effect on the angles < 30° and > 90°. Therefore, CSA should be considered when selecting the lens size using the KS formula preoperatively. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065501.
Subject(s)
Lens, Crystalline , Phakic Intraocular Lenses , Humans , Lens Implantation, Intraocular/methods , Visual Acuity , Eye , Retrospective StudiesABSTRACT
BACKGROUND: Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. METHOD: Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. RESULTS: Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. CONCLUSION: This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.
Subject(s)
Femur Head Necrosis , Protein Interaction Maps , Animals , Femur Head Necrosis/chemically induced , Femur Head Necrosis/genetics , Femur Head Necrosis/immunology , Humans , Biomarkers/metabolism , Gene Expression Profiling , Disease Models, Animal , Computational Biology , Gene Regulatory Networks , Mice , Male , Steroids , Machine Learning , Signal Transduction/geneticsABSTRACT
INTRODUCTION: This study aimed to compare the accuracy of seven implantable collamer lens (ICL) implantation vault prediction formulae. METHODS: We retrospectively analyzed 328 patients (328 eyes) who underwent ICL implantation and the prediction accuracy of seven formulae: NK, KS, WH, Luo, Zhu, Hun, and ZZ were compared. Moreover, the accuracy of the seven formulae for different ICL sizes was compared. The formulae were tested using mean absolute prediction error (MAE), median absolute prediction error (MedAE), prediction error (PE) percentages at ± 50 µm, ± 100 µm, ± 200 µm, and ± 300 µm, and Bland-Altman analysis. RESULTS: The PE of the seven formulae were statistically significant (P < 0.001). The KS (101.00 µm) and WH formulae (116.65 µm) had the smallest MedAE, followed by the Luo (123.62 µm), NK (141.50 µm), Hun (152.68 µm), ZZ (196.00 µm) and Zhu formula (225.98 µm). The highest percentage of PE in the range of ± 300µm was 94.3% and 93% for the KS and WH formulae, respectively. Among the different ICL size groupings, the KS formula predicted the smallest MedAE for 12.1 mm and 12.6 mm, whereas the Luo and WH formulae predicted the smallest MedAE for 13.2 mm and 13.7 mm, respectively. CONCLUSIONS: The KS and WH formulae provided better outcomes by predicting the vault with higher accuracy than of the NK, Hun, Luo, ZZ, and Zhu formulae. TRIAL REGISTRATION: ChiCTR2200065501.
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PURPOSE: To investigate the factors affecting footplate position and its influence on vault characteristics following implantable collamer lens (ICL) implantation. SETTING: Hunan Provincial People's Hospital, Changsha, China. DESIGN: Retrospective case series. METHODS: This study included 124 patients (124 eyes). Ultrasound biomicroscopy (UBM) was performed to assess the iris and ciliary body morphologies and observe the footplate position. Using multiple linear regression, the relationship between various ocular and ICL parameters and the vault as well as the factors affecting the footplate distance (FD) were analyzed. Based on the FD, three groups were formed: group 1 (<500 µm), group 2 (500-1000 µm), and group 3 (>1000 µm). The distribution of the vault range after surgery was observed for the three groups. RESULTS: Ciliary sulcus angle and FD significantly impacted the vault (adjusted R2=0.190, F=6.763, P<0.001), with FD being the most important factor influencing the vault (Beta=-0.383, P<0.001). Postoperative UBM revealed that the footplate was located at different positions in the posterior chamber, with the majority (52%) being located on the ciliary body. The average size of the four footplate orientations was 0.88±0.24 mm. Multiple linear regression analysis revealed that ciliary body thickness (CBT), iris curvature (IC), and ICL iris contact length (IRCL) significantly influenced the FD (adjusted R2=0.373, F=11.432, P<0.001). The vault range differed significantly among the three groups (X2=32.33, P<0.001). CONCLUSIONS: Different postoperative ICL footplate positions significantly affect the vault. CBT, IC, and IRCL can alter the position of the footplate from the expected position. This study provides reference for ICL size selection and vault prediction.
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As a common treatment for rheumatoid arthritis (RA), the adverse reactions of TNF-α inhibitors (TNFis) in practical application have garnered attention. This study aims to investigate the adverse drug events (ADEs) associated with TNFi in RA patients as reported in the FDA Adverse Event Reporting System, to offer insights for clinical use. Cases related to RA and primarily involving TNFi were extracted from the FDA Adverse Event Reporting System database and compared by gender stratification. Screening was conducted based on reporting odds ratio and information component to identify positive ADEs for different TNFis and evaluate common and unique ADEs among various TNFis. There are 4 common ADEs among TNFis, including pulmonary tuberculosis, infection, hypersensitivity, and herpes zoster, as described in the package inserts. However, each TNFi has unique positive ADEs. Adalimumab has 63 unique positive ADEs, including lower respiratory tract inflammation, systemic lupus erythematosus rash, vascular dementia, ovarian neoplasm, adhesion, sarcoma, coccidioidomycosis, etc. Golimumab has 6 unique positive ADEs, including pneumonia cryptococcal, device deployment issue, pneumonia bacterial, polyneuropathy, device malfunction, device issue, etc; certolizumab has 24 unique positive ADEs, including maternal exposure before pregnancy, premature rupture of membranes, exposure via breast milk, staphylococcal sepsis, erysipelas, low birth weight baby, herpes virus infection, premature delivery, etc; etanercept has 180 unique positive ADEs, including joint destruction, chondrolysis, finger deformity, ankle deformity, joint warmth, etc; infliximab has 60 unique positive ADEs, including Hodgkin's disease, metastatic neoplasm, non-Hodgkin's Lymphoma, etc. Although the aforementioned 5 TNFis share common ADEs such as herpes zoster, clinicians must exercise caution when selecting specific medications, especially for RA patients concurrently suffering from malignancies. The analysis indicates that infliximab is associated with 60 unique positive ADEs, including Hodgkin's disease, metastatic neoplasm, and non-Hodgkin's lymphoma; therefore, these patients should use infliximab with greater caution. Similarly, certolizumab should be used with increased caution in pregnant and postpartum women.
Subject(s)
Adverse Drug Reaction Reporting Systems , Arthritis, Rheumatoid , Tumor Necrosis Factor-alpha , United States Food and Drug Administration , Humans , United States/epidemiology , Female , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Male , Arthritis, Rheumatoid/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Antirheumatic Agents/adverse effects , Middle Aged , Antibodies, Monoclonal/adverse effects , Adalimumab/adverse effects , AdultABSTRACT
Type 2 diabetes mellitus (T2DM) is a progressive disease. We utilized bioinformatics analysis and experimental research to identify biomarkers indicative of the progression of T2DM, aiming for early detection of the disease and timely clinical intervention. Integrating Mfuzz analysis with differential expression analysis, we identified 76 genes associated with the progression of T2DM, which were primarily enriched in signaling pathways such as apoptosis, p53 signaling, and necroptosis. Subsequently, using various analytical methods, including machine learning, we further narrowed down the hub genes to STK17A and CCT5. Based on the hub genes, we calculated the risk score for samples and interestingly found that the score correlated with multiple programmed cell death (PCD) pathways. Animal experiments revealed that the diabetes model exhibited higher levels of MDA and LDH, with lower expression of SOD, accompanied by islet cell apoptosis. In conclusion, our study suggests that during the progression of diabetes, STK17A and CCT5 may contribute to the advancement of the disease by regulating oxidative stress, programmed cell death pathways, and critical signaling pathways such as p53 and MAPK, thereby promoting the death of islet cells. This provides substantial evidence in support of further disease prevention and treatment strategies.
Subject(s)
Diabetes Mellitus, Type 2 , Glucose Intolerance , Animals , Diabetes Mellitus, Type 2/metabolism , Glucose Intolerance/metabolism , Tumor Suppressor Protein p53/genetics , Biomarkers , Computational BiologyABSTRACT
BACKGROUND: Ranitidine induced tumor adverse events remains a contradictory clinical question, due to the limited evidence of tumor risk associated with ranitidine in the real world. The purpose of this study was to evaluate the association of ranitidine with all types of tumors through the FAERS database and to provide a reference for clinical use. RESEARCH DESIGN AND METHODS: Cancer cases associated with ranitidine in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023 were extracted to analyze demographic characteristics, and a disproportion analysis was performed. RESULT: A total of 662,998 ranitidine-related cancer cases were screened, and the 50-59 and 60-69 groups accounted for the largest proportion. In PT signal detection, ranitidine was associated with 98 PT, including penal cancer stage II, gastric cancer stage II, et al. In terms of outcome events, adverse events were higher in men (20.65%) than in women (18.47%). CONCLUSIONS: Ranitidine may induce various tumor-related adverse reactions, especially in long-term users and elderly patients. For these patients, tumor screening should be strengthened, and long-term use of ranitidine should be avoided. Since this study cannot prove causality, further evidence is needed for prospective studies with a larger sample size.
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Hepatocellular carcinoma (HCC) remains a global medical problem. Programmed cell death protein 1 (PD-1) is a powerful weapon against many cancers, but it is not sensitive to some patients with HCC. We obtained datasets from the Gene Expression Omnibus (GEO) database on HCC patients and PD-1 immunotherapy to select seven intersecting DEGs. Through Lasso regression, two intersecting genes were acquired as predictors of HCC and PD-1 treatment prognosis, including HAMP and FOS. Logistic regression was performed to build a prediction model. HAMP had a better ability to diagnose HCC and predict PD1 treatment sensitivity. Further, we adapted the support vector machine (SVM) technique using HAMP to predict triple-classified outcomes after PD1 treatment in HCC patients, which had an excellent classification ability. We also performed external validation using TCGA data, which showed that HAMP was elevated in the early stage of HCC. HAMP was positively correlated with the infiltration of 18 major immune cells and the expression of 2 important immune checkpoints, PDCD1 and CTLA4. We discovered a biomarker that can be used for the early diagnosis, prognosis and PD1 immunotherapy efficacy prediction of HCC for the first time and developed a diagnostic model, prognostic model and prediction model of PD1 treatment sensitivity and treatment outcome for HCC patients accordingly.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Programmed Cell Death 1 Receptor , Prognosis , Immunotherapy , HepcidinsABSTRACT
Background: To derive and validate a novel vault prediction formula to improve the predictability and safety of implantable collamer lens (ICL) implantation. Methods: Thirty-five patients (61 eyes) with previous posterior chamber intraocular lens implantation were included. Various parameters, such as horizontal-visible iris diameter (HVID), photopic pupil diameter (PPD), axial length (AL), white-to-white (WTW), anterior chamber width (ACW), angle-to-angle (ATA), crystalline lens rise (CLR), anterior chamber depth (ACD), horizontal sulcus-to-sulcus (HSTS), and ciliary sulcus angle (CSA) were measured. Vault was measured at 3 months after surgery using CASIA2 anterior segment optical coherence tomography. The formula was derived using multiple linear regression analysis and named as WH formula. It was validated in 65 patients (118 eyes) to determine the percentage of the ideal postoperative vault range and to compare the differences between the WH formula and the NK, KS, and STAAR formulas. Results: Final ICL size, ATA, CSA, and CLR were included in the prediction formula model (adjusted R2 = 0.67, p < 0.001). The achieved vault 1 month after the surgery was 556.19 µm ± 166.98 µm in the validation group, and the ideal vault range was 200-800 µm (92%). The difference between the achieved vault and that predicted using the WH formula was not statistically significant (p = 0.165), whereas the difference between the achieved vault and that predicted using the NK and KS formulas was statistically significant (p < 0.001 and p < 0.001, respectively). The 95% agreement limit range of the achieved vault and the vault predicted using the WH formula was narrower than those predicted using the NK and KS formulas (-295.20-258.82 µm). Conclusion: This study combined the results of optical coherence tomography and ultrasound biomicroscopy measurements of the anterior segment of the eye and incorporated ciliary sulcus morphology quantification into the prediction formula. The study derived a prediction formula for vault by combining ICL size, ATA, and CLR. The derived formula was found to be superior to the currently available formulas.
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Gastric cancer (GC) is the fifth most common cancer worldwide. Cuproptosis is associated with cell growth and death as well as tumorigenesis. Aiming to lucubrate the potential influence of CRGs in gastric cancer, we acquired datasets of gastric cancer patients from TCGA and GEO. The identification of molecular subtypes with CRGs expression was achieved through unsupervised learning-cluster analysis. To evaluate the application value of subtypes, the K-M survival analysis was conducted to evaluate the clinical prognostic characteristics. Subsequently, we performed Gene Set Variation Analysis (GSVA) and utilized ssGSEA to quantify the extent of immune infiltration. Further, the K-M survival analysis was used to identify the prognosis-related CRGs. Next, signature genes of diagnostic predictive value were screened using the least absolute shrinkage and selection operator (LASSO) algorithm from the expression matrix for TCGA, as well as the signature gene-related subtype was clustered by the "ConsensusClusterPlus" package. Finally, the immunological and drug sensitivity assessments of the signature gene-related subtypes were conducted. A total of 173 CRGs were identified, most of the CRGs undergo copy number variation in gastric cancer. Under different patient subtypes, immune cell levels differed significantly, and the subtype exhibiting high expression of the CRGs had a better prognosis. Furthermore, we selected 34 CRGs that were highly correlated with the prognosis of gastric cancer. By constructing a multivariate Cox proportional-hazards model and a hazard scoring system, we were able to categorize patients into high- and low-risk groups based on their hazard score. K-M analysis demonstrated a significant survival disadvantage in the high-risk group. Based on Lasso regression analysis, we screened 16 signature genes, a multivariate logistic regression model [cutoff: 0.149 (0.000, 0.974), AUC:0.987] and a prognosis network diagram was constructed and their prediction efficiency for gastric cancer prognostic diagnosis was well validated. According to the signature genes, the patients were separated to two signature subtypes. We found that patients with higher CRGs expression and better prognosis had lower levels of immune infiltration. Finally, according to the results of drug susceptibility analysis, docetaxel, 5-Fluorouracil, gemcitabin, and paclitaxel were found to be more sensitive to gastric cancer.
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BACKGROUND: From the end of 2019 to now, COVID-19 is still prevalent, which poses a great threat to international public health. With the increasing number of people infected, the number of patients with COVID-19 sequelae is also increasing, but there is no specific drug for COVID-19 sequelae. In China, traditional Chinese medicine combined with acupuncture has been widely used in COVID-19 sequelae, but there is still a lack of evidence-based medicine evaluation. The purpose of this study was to evaluate the efficacy and safety of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. METHODS: According to the retrieval strategy, the "long COVID" randomized controlled trial of traditional Chinese medicine combined with moxibustion will be search in eight databases composed of PubMed, Embase, Web of Science, China National knowledge Infrastructure Database, China Biomedical Database and China Science and Technology Journal Database, regardless of publication date or language. The study was screened according to the inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the study. Meta-analysis was carried out using RevMan5.3 and STATA12.0 software. Finally, the level of evidence of the results will be evaluated. RESULTS: This study will evaluate whether traditional Chinese medicine combined with moxibustion can effectively treat the symptoms of COVID-19 sequelae. CONCLUSION: This study will provide evidence whether there is benefit of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. At the same time, our research results will provide a reference for clinical decision-making and guiding development in the future.
Subject(s)
COVID-19 , Moxibustion , Humans , Moxibustion/methods , Medicine, Chinese Traditional/methods , COVID-19/therapy , Systematic Reviews as Topic , Meta-Analysis as Topic , Research Design , Post-Acute COVID-19 SyndromeABSTRACT
Objectives: To describe the epidemiological characteristics and medication overview of HFMD in Guangzhou and analyze the factors of length of stay (LOS) based on TCM usage. Method: From January 1, 2014, to June 30, 2019, clinical data of HFMD (ICD-10 B08.401) as the initial diagnosis, based on HIS of five medical institutions for outpatient and inpatient cases, was collected. The inpatient cases of the five hospitals in Guangzhou were utilized for hospitalization analysis. Information extracted from the warehouse was standardized. Descriptive analysis was used for baseline characteristics, medication usage, and inpatient characteristics. Potential factors were analyzed by bivariate analysis. COX regression analysis and Kaplan-Meier analysis for calculating HRs and 95% CIs were adopted to determine the predictors of LOS. Stratified COX regression was applied to analyze the relationship between predictors and LOS and to calculate interaction. Results: A total of 14172 patients with HFMD were included. It showed that HFMD would occur in males, infants, and summer. Cause and symptoms are the two aspects of conventional Western medicine treatments, while TCM treatment of HFMD took clearing heat and detoxification as the basic principle. Inpatients with HFMD were divided into two groups by the use ratio of TCM. Age, season, and disease severity were possible correlated factors of LOS, extrapolating from their disparity in distribution. By stratified Cox regression, three factors following presented as possible contributions to shortening LOS, including TCM ≥ 0.1 (HR = 1.79, 95% CI (1.67-1.92), P < 0.01), winter (HR = 1.28, 95% CI (1.12-1.47)), P < 0.01), mild HFMD (HR = 1.93, 95% CI (1.69-2.22), P < 0.01). Additive interaction of TCM use and disease severity was significant (RERI = 1.014 (0.493-1.534), P < 0.01). Conclusion: Young children and high temperature were the risk factors of HFMD infection, which suggests that increasing surveillance for susceptible particular-age individuals and season is indispensable. Favorable factors to decrease LOS included a higher proportion of TCM use, mild HFMD, and onset in winter. The proportion of TCM use had additive interaction with disease severity, indicating that TCM may have antiviral and other biological effects on HFMD. Increasing the proportion of TCM use was probably beneficial to shortening LOS.
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Background: Glypican 2 (GPC2), a member of glypican (GPC) family genes, produces proteoglycan with a glycosylphosphatidylinositol anchor. It has shown its ascending significance in multiple cancers such as neuroblastoma, malignant brain tumor, and small-cell lung cancer. However, no systematic pan-cancer analysis has been conducted to explore its function in diagnosis, prognosis, and immunological prediction. Methods: By comprehensive use of datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), UALCAN, StarBase, and Comparative Toxicogenomics Database (CTD), we adopted bioinformatics methods to excavate the potential carcinogenesis of GPC2, including dissecting the correlation between GPC2 and prognosis, gene mutation, immune cell infiltration, and DNA methylation of different tumors, and constructed the competing endogenous RNA (ceRNA) networks of GPC2 as well as explored the interaction of GPC2 with chemicals and genes. Results: The results indicated that GPC2 was highly expressed in most cancers, except in pancreatic adenocarcinoma, which presented at a quite low level. Furthermore, GPC2 showed the early diagnostic value in 16 kinds of tumors and was positively or negatively associated with the prognosis of different tumors. It also verified that GPC2 was a gene associated with most immune-infiltrating cells in pan-cancer, especially in thymoma. Moreover, the correlation with GPC2 expression varied depending on the type of immune-related genes. Additionally, GPC2 gene expression has a correlation with DNA methylation in 20 types of cancers. Conclusion: Through pan-cancer analysis, we discovered and verified that GPC2 might be useful in cancer detection for the first time. The expression level of GPC2 in a variety of tumors is significantly different from that of normal tissues. In addition, the performance of GPC2 in tumorigenesis and tumor immunity also confirms our conjecture. At the same time, it has high specificity and sensitivity in the detection of cancers. Therefore, GPC2 can be used as an auxiliary indicator for early tumor diagnosis and a prognostic marker for many types of tumors.
Subject(s)
Adenocarcinoma , Glypicans/analysis , Pancreatic Neoplasms , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Glypicans/genetics , Humans , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , PrognosisABSTRACT
AIM: To compare clinical outcomes and refractive stability of implantable collamer lens (ICL) implantation and femtosecond laser assisted laser in situ keratomileusis (FS-LASIK) for high myopia correction. METHODS: The Optical Quality Analysis System (OQAS) was used to evaluate clinical outcomes objectively after operation for high myopia correction. We compared the two procedures in terms of 1-year changes in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), safety index, efficacy index, spherical equivalent, modulation transfer function (MTF) cutoff frequency, strehl ratio (SR) and objective scatter index (OSI). RESULTS: At 1y postoperatively, the safety indices were 1.33±0.27 in ICL group, and 1.17±0.24 in FS-LASIK group. 39.58% in the ICL group and 27.59% in the FS-LASIK group gained CDVA in 2 lines or better than that in preoperative CDVA. The efficacy indices were 1.28±0.22 in ICL group, and 1.13±0.26 in FS-LASIK group. The changes of spherical equivalent from 1wk to 1y postoperatively was -0.12±0.37 D in ICL group, and -0.79±0.58 D in FS-LASIK group (P<0.05). Spherical equivalent within ±0.50 D was achieved in 97.92% in ICL group and 68.97% in FS-LASIK group. MTF cutoff frequency were higher with ICL as compared to FS-LASIK (P<0.05) at each postoperative follow-up stage; for postoperative 1mo later, SR was statistically significant difference between two groups (P<0.05); with no statistically significant difference in OSI between two groups (P>0.05) in postoperative 3mo later. CONCLUSION: ICL implantation and FS-LASIK procedures both provide good safety and predictability in high myopia correction. ICL implantation provides better clinical outcomes and refractive stability than FS-LASIK.
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BACKGROUND: Insomnia is a prevalent and bothersome disorder of sleep initiation and maintenance. Although efficacious treatments for insomnia have been available for decades, they all have their own limitations. Guizhi Gancao Longgu Muli Decoction (GGLMD), a popular complementary and alternative therapy, has been widely applied to treat insomnia in some Asian countries for centuries. Yet no systematic reviews have comprehensively assessed the efficacy and safety of GGLMD as a treatment for insomnia. METHODS: A comprehensive search up to November, 2019 will be conducted in the following electronic databases: the Cochrane Library, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), the Chinese Scientific Journal Database (VIP), and the Wanfang Database. The primary outcomes will be sleep quality including Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG). Stata 15 will be used for data analysis as well. RESULTS: This study will provide the current evidence of insomnia treated with GGLMD from the several points including PSQI and PSG. CONCLUSION: The consequence of this summary will furnish proof to evaluate if GGLMD is effective in the treatment of insomnia. ETHICS AND DISSEMINATION: Without personal information involved, ethical approval and informed consent form is no need. The review will be submitted to a peer-reviewed journal prospectively to spread our findings. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018118336.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Humans , Systematic Reviews as TopicABSTRACT
PURPOSE:: To investigate the safety and efficacy of implanting a posterior chamber implantable collamer lens with a central hole in cases of high myopia with peripheral primary iris or ciliary body cysts. METHODS:: A total of 37 eyes of 19 patients with primary iris or ciliary body cysts detected by ultrasonic biological microscope were included, with spherical powers of -10.26 ± 3.28 D and cylinder powers of -1.71 ± 1.18 D. Each patient received ultrasonic biological microscope and a routine examination before implantation of the implantable collamer lens. A routine postoperative follow-up was performed to observe changes in the iris or ciliary body cyst, ranging from 3 to 18 months. RESULTS:: There were no complications. At the last follow-up, 56.8% (21/37) of eyes achieved the same corrected distance visual acuity as their preoperative measurements, 43.2% of eyes were enhanced by ≥1 line, and no patients' corrected distance visual acuity declined. The efficacy index and safety index were 0.95 and 1.11, respectively. After 18 months, 66.7% of the spherical equivalents were between ±0.5 D with 100% between ±1.0 D. The postoperative mean spherical equivalents at 1, 3, 6, 12, and 18 months were -0.45 ± 0.31 D, -0.39 ± 0.29 D, -0.36 ± 0.30 D, -0.39 ± 0.38 D, and -0.48 ± 0.23 D (p = 0.789). The vaults were 516 ± 140, 548 ± 124, 498 ± 133, 582 ± 161, and 557 ± 110 µm (p = 0.355). There were no changes in size (p > 0.05), number, or position of the iris or ciliary body cysts. CONCLUSION:: Implantable collamer lens implantation is safe and effective for highly myopic patients with peripheral primary iris and ciliary body cysts. The cysts did not change after operation in this study.
Subject(s)
Ciliary Body/surgery , Cysts/surgery , Iris Diseases/surgery , Lens Implantation, Intraocular/methods , Myopia/surgery , Phakic Intraocular Lenses , Refraction, Ocular/physiology , Adult , Cysts/complications , Cysts/diagnosis , Female , Humans , Iris/pathology , Iris/surgery , Iris Diseases/complications , Iris Diseases/diagnosis , Male , Middle Aged , Myopia/complications , Myopia/physiopathologyABSTRACT
OBJECTIVE: To investigate the effects of Laser in situ keratomileusis (LASIK) for treatment of presbyopia with hypermetropia. METHODS: 32 presbyopia patients (64 eyes) with hypermetropia were treated by LASIK and follow-up 1 year. The preoperative sphere was +0.75 to +3.00 D and cylinder was 0.00 to +1.75 D. For distance vision correction, the target refraction was 0.00 to -0.50 D in the dominant eye. And for near vision, the target refraction was -1.50 to -2.50 D in the non-dominant eye. The measurement including refraction, uncorrected visual acuity (UCVA), near vision, Q factor of cornea and contrast sensitivity were recorded. RESULTS: At 1 year after surgery a total of 53.1% (17/32) of all patients had binocular distance UCVA of 20/25 or better along with J3 or better near, and along with J4 or better near was 87.5% (28/32). The postoperative corneal refractive power was significant higher than preoperative [3 mm: (44.12 +/- 1.38) D, 5 mm: (43.42 +/- 1.53) D] and Q factor became more negative. At 1 year 87.5% (28/32) and 100.0% (32/32) of the dominant eyes treated for distance had a manifest refractive spherical equivalent within +/- 0.50 and +/- 1.00 D of intended correction, respectively; of the non-dominant eyes treated for near, 56.2% (18/32) and 90.6% (29/32) had a manifest refractive spherical equivalent within +/- 0.50 and +/- 1.00 D of intended correction respectively. The difference of sensitivity was no statistically significant between preoperative and 6 months after surgery. There were 15.6% of the eyes had dry eye syndrome and 84.4% of the patients were satisfied with LASIK at 1 year after surgery. CONCLUSIONS: LASIK was a effect surgery for treatment of presbyopia with hypermetropia.
Subject(s)
Hyperopia/surgery , Keratomileusis, Laser In Situ , Presbyopia/surgery , Female , Humans , Hyperopia/complications , Keratomileusis, Laser In Situ/methods , Middle Aged , Presbyopia/complicationsABSTRACT
OBJECTIVE: To investigate the expression and significance of matrix metalloproteinase-3 (MMP-3), osteopontin (OPN) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human lens epithelial cells (LECs) of cataract. METHODS: The MMP-3, OPN, and TIMP-1 expressions in LECs of anterior subcapsular cataract (31 cases), nuclear cataract (28 cases) and normal lens (12 cases) were detected by immunohistochemistry, respectively. RESULTS: The MMP-3 expression in anterior subcapsular cataract was significantly higher than that in nuclear cataract and normal lens (chi2=31.49, 34.479; P=0.000); but there was no statistic significance between nuclear cataract and normal lens (chi2=2.449, P=0.118). The OPN expression in anterior subcapsular cataract was also significantly higher than that in nuclear cataract and normal lens (chi2=29.450, 15.889; P=0.000). There was no significant difference in the TIMP-1 expression among the 3 groups (P>0.05). Positive correlation was found between MMP-3 and OPN in LECs of anterior subcapsular cataract (r=0.381, P=0.035). But no significant correlation was found among MMP-3, OPN, and TIMP-1 (r=0.121, -0.289; P=0.516, 0.114). CONCLUSION: Increased expression of MMP-3 and OPN and the expression imbalance between MMP-3 and TIMP-1 may play a critical role in the pathogenesis of anterior subcapsular cataract.