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Sepsis is a life-threatening condition that occurs when the body's normal response to an infection is out of balance. A key part of managing sepsis involves the administration of intravenous fluids and vasopressors. In this work, we explore the application of G-Net, a deep sequential modeling framework for g-computation, to predict outcomes under counterfactual fluid treatment strategies in a real-world cohort of sepsis patients. Utilizing observational data collected from the intensive care unit (ICU), we evaluate the performance of multiple deep learning implementations of G-Net and compare their predictive performance with linear models in forecasting patient outcomes and trajectories over time under the observational treatment regime. We then demonstrate that G-Net can generate counterfactual prediction of covariate trajectories that align with clinical expectations across various fluid limiting regimes. Our study demonstrates the potential clinical utility of G-Net in predicting counterfactual treatment outcomes, aiding clinicians in informed decision-making for sepsis patients in the ICU.
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Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Hydroxychloroquine , Hyperpigmentation , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Aged , Female , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Hyperpigmentation/chemically induced , Hyperpigmentation/diagnosis , Arthritis, Rheumatoid/drug therapy , Skin/pathology , Skin/drug effectsABSTRACT
Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with colonic crypts (CC) being crucial in its development. Accurate segmentation of CC is essential for decisions CRC and developing diagnostic strategies. However, colonic crypts' blurred boundaries and morphological diversity bring substantial challenges for automatic segmentation. To mitigate this problem, we proposed the Dual-Branch Asymmetric Encoder-Decoder Segmentation Network (DAUNet), a novel and efficient model tailored for confocal laser endomicroscopy (CLE) CC images. In DAUNet, we crafted a dual-branch feature extraction module (DFEM), employing Focus operations and dense depth-wise separable convolution (DDSC) to extract multiscale features, boosting semantic understanding and coping with the morphological diversity of CC. We also introduced the feature fusion guided module (FFGM) to adaptively combine features from both branches using cross-group spatial and channel attention to improve the model representation in focusing on specific lesion features. These modules are seamlessly integrated into the encoder for effective multiscale information extraction and fusion, and DDSC is further introduced in the decoder to provide rich representations for precise segmentation. Moreover, the local multi-layer perceptron (LMLP) module is designed to decouple and recalibrate features through a local linear transformation that filters out the noise and refines features to provide edge-enriched representation. Experimental evaluations on two datasets demonstrate that the proposed method achieves Intersection over Union (IoU) scores of 81.54% and 84.83%, respectively, which are on par with state-of-the-art methods, exhibiting its effectiveness for CC segmentation. The proposed method holds great potential in assisting physicians with precise lesion localization and region analysis, thereby improving the diagnostic accuracy of CRC.
Subject(s)
Colon , Coping Skills , Colon/diagnostic imaging , Information Storage and Retrieval , Neural Networks, Computer , Semantics , Image Processing, Computer-AssistedABSTRACT
PURPOSE: The application of platinum-based chemotherapeutic agents is the traditional treatment paradigm for advanced and metastatic urothelial carcinoma, which has changed with the advent of immune checkpoint inhibitors (ICIs). This study aims to evaluate the efficacy of ICI therapy versus chemotherapy in the treatment of advanced and metastatic urothelial carcinoma. METHODS: A systematic literature search of Web of Science, Embase, PubMed, and Cochrane Central Register of Controlled Trials was performed by two independent investigators. The primary endpoint was overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: The patients treated with ICI monotherapy had no significant difference in OS than those treated with chemotherapy monotherapy (HR: 0.965, 95% CI 0.865-1.076, p = 0.518). However, the patients treated with ICI monotherapy had a higher ORR and lower incidence of high-grade (≥ grade 3) AEs than those treated with chemotherapy monotherapy (OR: 0.568, 95% CI 0.479-0.675, p < 0.001; OR: 0.614, 95% CI 0.446-0.845, p = 0.003). The patients treated with ICI in combination with chemotherapy had significantly better OS and PFS than those treated with chemotherapy alone (HR: 0.862, 95% CI 0.776-0.957, p = 0.006; HR: 0.788, 95% CI 0.707-0.879, p < 0.001). However, there was no significant difference in ORR or the incidence of grade 3 or higher AEs (OR: 0.951, 95% CI 0.582-1.554, p = 0.841; OR: 0.942, 95% CI 0.836-1.062, p = 0.328). CONCLUSION: ICI monotherapy did not show statistically significant difference in OS but demonstrated higher ORR and lower incidence of high-grade (≥ grade 3) AEs. And a statistically significant OS and PFS benefit was found in patients treated with first-line ICI in combination with chemotherapy compared to chemotherapy alone.
Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Carcinoma, Transitional Cell/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Platinum , Progression-Free SurvivalABSTRACT
We performed the first sequencing of the complete mitogenome of Botyodes diniasalis by high-throughput sequencing. A circular DNA molecule of 15,219 bp in size, encoding 2 rRNAs, 22 tRNAs, and 13 PCGs, contains a non-coding AT-rich region. The overall nucleotide composition of the genome is A (39.5%), T (41.3%), C (11.3%), and G (7.8%). Phylogenetic analysis based on mitogenomic data suggest that the species B. diniasalis has a close evolutionary relationship with B. principalis in Margaroniini. The complete mitogenome of B. diniasalis will serve as a valuable resource for future studies on evolution, taxonomy, genetic conservation, and utilization of Botyodes.
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RATIONALE: Acute generalized exanthematous pustulosis (AGEP) is a serious adverse skin reaction characterized by the rapid appearance of densely distributed, small, sterile pustules with erythema. However, its pathogenesis is not fully understood. Hydroxychloroquine is widely used for the treatment of autoimmune diseases. Some patients presenting with AGEP have IL36RN and CARD14 gene mutations. Our report describes a patient with rheumatoid arthritis and AGEP associated with hydroxychloroquine and a newly discovered CARD14 gene mutation. PATIENT CONCERNS: A 28-year-old woman with rheumatoid arthritis, treated with leflunomide therapy without marked relief of joint pain, developed multiple rashes with pruritis covering the body 5 days after switching to hydroxychloroquine treatment. DIAGNOSES: Based on the patient's history, symptoms, and histopathological findings, AGEP was diagnosed. INTERVENTIONS: Whole-exome sequencing and Sanger validation revealed no mutations in the IL36RN gene; however, a CARD14 gene mutation was present. The patient was treated using ketotifen fumarate tablets, dexamethasone sodium phosphate, calcium gluconate injection, methylprednisolone injection, vitamins C and B12, hydrocortisone butyrate cream, Reed acne cream, potassium chloride tablets, and pantoprazole enteric-coated capsules. OUTCOMES: The rash improved after 15 days. LESSONS SUBSECTIONS: There has been little basic research on AGEP-related genetics, and the CARD14 mutation may underlie several pustular rashes, including AGEP and generalized pustular psoriasis. Follow-up studies and further accumulation of patient data are required.
Subject(s)
Acute Generalized Exanthematous Pustulosis , Arthritis, Rheumatoid , Exanthema , Female , Humans , Adult , Hydroxychloroquine/adverse effects , Acute Generalized Exanthematous Pustulosis/etiology , Skin/pathology , Arthritis, Rheumatoid/complications , Exanthema/chemically induced , Mutation , Guanylate Cyclase/genetics , Membrane Proteins/genetics , CARD Signaling Adaptor Proteins/genetics , Interleukins/geneticsABSTRACT
BACKGROUND: Although androgenetic alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, changes in the immune microenvironment, immune-related pathways and the expression of immune-related genes (IRGs) involved in AGA remain unclear. METHODS: The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. gene set enrichment analysis (GSEA) among statistically changed genes was done. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses among differentially expressed genes were performed. differentially expressed genes were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells. RESULTS: The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The 4 hub IRGs, including matrix metallopeptidase 9, protein tyrosine phosphatase receptor type C, bone morphogenetic protein 2, and thrombospondin 1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response. CONCLUSION: In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.
Subject(s)
Alopecia , Interferon-gamma , Humans , Male , Alopecia/genetics , Mast Cells , Algorithms , Blood CoagulationABSTRACT
Circular RNA (circRNA) molecules are noncoding RNAs with ring-like structures formed by covalent bonds and are characterized by no 5'caps or 3'polyadenylated tails. Increasing evidence shows that circRNAs may play an important role in tumorigenesis and cancer metastasis. Circ-SHPRH originates from exons 26-29 of the SHPRH gene, and it is closely associated with human cancers. We searched PubMed, Web of Science, and Embase databases for relevant literatures until 24 December 2022. Eighteen research papers were included in this review, and 11 papers were selected for meta-analysis after screening. Three eligible published studies about circ-SHPRH were enrolled based on their tumor diagnosis aspect, 7 eligible published studies were related to overall survival (OS), and 3 eligible published studies were related to tumor grade. Many studies have shown that circ-SHPRH acts as a miRNA sponge or encodes a protein to regulate downstream genes or signal pathways, and exerts specific biological functions that affect the proliferation, invasion, and apoptosis of cancer cells. Meta-analysis showed that patients with high expression of circ-SHPRH had better OS (HR = 0.53, 95% CI 0.38-0.74, p-value <0.05) and lower TNM stage (HR = 0.33, 95% CI 0.18-0.62, p-value = 0.001). In addition, circ-SHPRH has potential diagnostic value (AUC = 0.8357). This review will help enrich our understanding of the role and mechanism of circ-SHPRH in human cancers. Circ-SHPRH has the potential to be a novel diagnostic and prognostic biomarker for various solid cancers.
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BACKGROUND: Vaccination is the most effective way to prevent coronavirus disease 2019 (COVID-19). However, it is often less protective and does not significantly increase antibody levels, especially in individuals with impaired immune systems. Nevertheless, the immunocompetence can be enhanced using a natural immunomodulator, such as Dendrobium officinale aqueous extract (DoAE). METHODS: To determine whether DoAE promotes antibody production, we treated healthy volunteers with DoAE during COVID-19 vaccination. Meanwhile, the control volunteers were given a placebo (cornstarch) during the vaccination. Antibody levels were measured at three-week intervals in the DoAE and control groups. RESULTS: DoAE enhanced immunity and preserved immune cell homeostasis. However, the neutralizing antibody (nAb) levels in the DoAE group were lower than those in the control group. Analysis of the gut microbiota revealed that the abundance of anti-inflammatory flora was increased, while the pro-inflammatory flora was reduced in the DoAE group. CONCLUSION: DoAE has immunomodulatory and anti-inflammatory properties. Therefore, DoAE has the potential for COVID-19 prophylaxis, treatment, and recovery from the adverse effects of COVID-19. However, its anti-inflammatory activity affects the production of nAbs. Thus, DoAE may not be recommended for consumption during COVID-19 vaccination.
Subject(s)
COVID-19 , Dendrobium , Humans , Adjuvants, Immunologic , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , SARS-CoV-2 , VaccinationABSTRACT
Introduction: Acute generalized exanthematous pustulosis (AGEP) is a rare condition characterized by superficial pustules following drug ingestion or infection. Currently, there is no clear link between rheumatism and AGEP. It has been described that hydroxychloroquine (HCQ) is a rare cause of acute generalized epidermal necrolysis (AGEP). Presently, there are limited studies on HCQ-induced AGEP. We aimed to explore the clinical features and associated gene expression of AGEP induced after HCQ treatment exposure in rheumatology patients. Methods: We assessed patients with HCQ-induced AGEP diagnosed at the Second Affiliated Hospital of Guizhou University of Chinese Medicine between January 1, 2017, and May 1, 2022. We also reviewed similar cases reported in specific databases. Results: The study included five females (mean age, 40.2 years), and the mean time from initiation of HCQ treatment to symptom onset was 12.2 d. All patients received steroids and allergy medications after HCQ discontinuation, and the rash completely resolved within an average of 25.2 d. We performed whole exome sequencing and Sanger validation in our patient sample. CARD14 gene mutations were detected in three patients. Additionally, seven mutation sites were detected. Discussion: HCQ-induced AGEP may have a longer latency period and regression time than AGEP induced by other drugs. Our patients all experienced CARD14 gene mutations. AGEP often resolves with topical therapy and drug discontinuation, although some cases require systemic steroid therapy. In the future, patients with rheumatism should pay attention to the effectiveness of HCQ during treatment and be aware of the associated skin toxicity.
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Superselective adrenal arterial embolization (SAAE) appears to be beneficial in primary aldosteronism (PA) patients with lateralized aldosterone secretion (unilateral PA). As confirmed by adrenal vein sampling (AVS), nearly 40% of PA patients would be PA without lateralized aldosterone secretion (bilateral PA). We aimed to investigate the efficacy and safety of SAAE on bilateral PA. We identified 171 bilateral PA patients from 503 PA patients who completed AVS. Thirty-eight bilateral PA patients received SAAE, and 31 completed a median 12-month clinical follow-up. The blood pressure and biochemical improvements of these patients were carefully analyzed. 34% of patients were identified as bilateral PA. Plasma aldosterone concentration, plasma renin activity, and aldosterone/renin ratio (ARR) were significantly improved 24-h after SAAE. SAAE was associated with 38.7% and 58.6% of complete/partial clinical and biochemical success within a median 12-month follow-up. A significant reduction in left ventricular hypertrophy was shown in patients who obtained complete biochemical success compared with partial/absent biochemical success. SAAE was associated with a more apparent nighttime blood pressure reduction than daytime blood pressure reduction in patients with complete biochemical success. No major adverse safety events related to SAAE were reported during the intraoperative, postoperative, and follow-up periods. SAAE was associated with blood pressure and biochemical improvements in part of bilateral PA and appeared safe. The biochemistry success was accompanied by improved cardiac remodeling and a more prominent decrease in nocturnal blood pressure. This study was part of a trial registered with the Chinese Clinical Trial Registry, number ChiCTR2100047689.
Subject(s)
Aldosterone , Hyperaldosteronism , Humans , Adrenal Glands/blood supply , Renin , Blood Pressure , Retrospective StudiesABSTRACT
Objectives: Compound Kushen injection (CKI) combined with intraperitoneal chemotherapy (IPC) is widely used in the treatment of malignant ascites (MA). However, evidence about its efficacy and safety remains limited. This review aimed to evaluate the efficacy and safety of CKI combined with IPC for the treatment of MA. Methods: Protocol of this review was registered in PROSPERO (CRD42022304259). Randomized controlled trials (RCTs) on the efficacy and safety of IPC with CKI for the treatment of patients with MA were searched through 12 electronic databases and 2 clinical trials registration platforms from inception until 20 January 2023. The Cochrane risk-of-bias tool was used to assess the quality of the included trials through the risk of bias assessment. We included RCTs that compared IPC single used or CKI combined with IPC for patients with MA schedule to start IPC. The primary outcome was identified as an objective response rate (ORR), while the secondary outcomes were identified as the quality of life (QoL), survival time, immune functions, and adverse drug reactions (ADRs). The Revman5.4 and Stata17 software were used to calculate the risk ratio (RR) at 95% confidence intervals (CI) for binary outcomes and the mean difference (MD) at 95% CI for continuous outcomes. The certainty of the evidence was assessed according to the GRADE criteria. Results: A total of 17 RCTs were assessed, which included 1200 patients. The risk of bias assessment of the Cochrane risk-of-bias tool revealed that one study was rated high risk and the remaining as unclear or low risk. Meta-analysis revealed that CKI combined with IPC had an advantage in increasing ORR (RR = 1.31, 95% CI 1.20 to 1.43, p < 0.00001) and QoL (RR = 1.50, 95% CI 1.23 to 1.83, p < 0.0001) when compared with IPC alone. Moreover, the combined treatment group showed a lower incidence of myelosuppression (RR = 0.51, 95%CI 0.40-0.64, p < 0.00001), liver dysfunction (RR = 0.33, 95%CI 0.16 to 0.70, p = 0.004), renal dysfunction (RR = 0.39, 95%CI 0.17 to 0.89, p = 0.02), and fever (RR = 0.51, 95%CI 0.35 to 0.75, p = 0.0007) compared to those of the control group. The quality of evidence assessment through GRADE criteria showed that ORR, myelosuppression, and fever were rated moderate, renal dysfunction and liver dysfunction were rated low, and QoL and abdominal pain were rated very low. Conclusion: The efficacy and safety of CKI combined with IPC were superior to that with IPC alone for the treatment of MA, which indicates the potentiality of the treatment. However, more high-quality RCTs are required to validate this conclusion. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304259], identifier [PROSPERO 2022 CRD42022304259].
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BACKGROUND: Enhancing the response rate of immunotherapy will aid in the success of cancer treatment. Here, we aimed to explore the combined effect of immunogenic radiotherapy with anti-PD-L1 treatment in immunotherapy-resistant HNSCC mouse models. METHODS: The SCC7 and 4MOSC2 cell lines were irradiated in vitro. SCC7-bearing mice were treated with hypofractionated or single-dose radiotherapy followed by anti-PD-L1 therapy. The myeloid-derived suppressive cells (MDSCs) were depleted using an anti-Gr-1 antibody. Human samples were collected to evaluate the immune cell populations and ICD markers. RESULTS: Irradiation increased the release of immunogenic cell death (ICD) markers (calreticulin, HMGB1 and ATP) in SCC7 and 4MOSC2 in a dose-dependent manner. The supernatant from irradiated cells upregulated the expression of PD-L1 in MDSCs. Mice treated with hypofractionated but not single-dose radiotherapy were resistant to tumour rechallenge by triggering ICD, when combined with anti-PD-L1 treatment. The therapeutic efficacy of combination treatment partially relies on MDSCs. The high expression of ICD markers was associated with activation of adaptive immune responses and a positive prognosis in HNSCC patients. CONCLUSION: These results present a translatable method to substantially improve the antitumor immune response by combining PD-L1 blockade with immunogenic hypofractionated radiotherapy in HNSCC.
Subject(s)
Head and Neck Neoplasms , Immune Checkpoint Inhibitors , Myeloid-Derived Suppressor Cells , Squamous Cell Carcinoma of Head and Neck , Animals , Humans , Mice , B7-H1 Antigen/metabolism , Head and Neck Neoplasms/drug therapy , Immunotherapy/methods , Myeloid-Derived Suppressor Cells/metabolism , Prognosis , Squamous Cell Carcinoma of Head and Neck/drug therapy , Immune Checkpoint Inhibitors/therapeutic useABSTRACT
Bladder cancer (BCa) is a malignant tumor that occurs in the bladder mucosa with high mortality. Circular RNAs (circRNAs), as newly discovered noncoding RNAs, are associated with the occurrence and development of BCa. However, the effects of circRNAs in BCa have not been fully elucidated. Through the GEO (Gene Expression Omnibus) database, an abnormally expressed circular RNA, circHGS (hsa_circ_0004721), was first identified in BCa. qRT - PCR was performed to measure the expression of circHGS in BCa tissues and cells. The intracellular localization of circHGS was detected by nucleocytoplasmic separation experiment and fluorescence in situ hybridization assay. In vitro experiments were conducted to detect the effects of circHGS on cell cycle, proliferation, migration and invasion. The correlations between miR-513a-5p and circHGS or VEGFC were confirmed by dual-luciferase reporter assay, qRT - PCR and western blot. The role of circHGS in vivo was verified by xenograft tumor mice model. In this study, we clarified the roles and potential mechanism of circHGS in BCa. CircHGS, originating from the HGS gene, is upregulated in BCa tissues compared to normal tissues. Moreover, the expression of circHGS in BCa was positively associated with tumor grade and pathological T stage. Functionally, silencing of circHGS apparently suppressed cell cycle, proliferation, migration and invasion, but circHGS overexpression showed the opposite result. In vivo experiments also suggested that knockdown of circHGS suppressed tumor growth. Mechanistically, circHGS functions as a sponge of miR-513a-5p to elevate VEGFC expression and activate the AKT/mTOR signaling pathway, ultimately promoting BCa progression. Our findings indicated that circHGS promotes BCa progression via the miR-513a-5p/VEGFC/AKT/mTOR pathway and can be a promising therapeutic target of BCa.
Subject(s)
MicroRNAs , Urinary Bladder Neoplasms , Animals , Humans , Mice , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Models, Animal , Gene Expression Regulation, Neoplastic , In Situ Hybridization, Fluorescence , MicroRNAs/genetics , MicroRNAs/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Signal Transduction/genetics , TOR Serine-Threonine Kinases/metabolism , Urinary Bladder Neoplasms/pathologyABSTRACT
Circular RNAs (circRNAs) are recognized as a novel type of single-stranded endogenous noncoding RNA molecule with the characteristics of tissue specificity, sequence conservation and structural stability. Accumulating studies have shown that circRNAs play a unique biological role in different kinds of diseases. CircRNAs can affect tumor proliferation, migration, metastasis and other behaviors by modulating the expression of downstream genes. CircSMARCA5, an example of a circRNA, is dysregulated in various noninfectious diseases, such as tumors, osteoporosis, atherosclerosis and coronary heart disease. Furthermore, recent studies have demonstrated that circSMARCA5 is associated with the occurrence and development of a variety of tumors, including gastric cancer, glioblastoma, hepatocellular carcinoma, multiple myeloma, colorectal cancer, breast cancer and osteosarcoma. Mechanistically, circSMARCA5 primarily acts as a sponge of miRNAs to regulate the expression of downstream genes, and can serve as a potential biomarker for the diagnosis of malignant tumors. This review summarizes the biological roles of circSMARCA5 and its molecular mechanism of action in various diseases. Moreover, the meta-analysis of some publications showed that the expression of circSMARCA5 was significantly correlated with the prognosis of patients and tumor TNM stage, showing that circSMARCA5 has the potential to be a prognostic marker.
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Background: The incidence of neovascular eye disease is increasing year by year, seriously threatening human vision health and becoming an urgent public health problem. Tongmai fuming decoction as an experienced prescription can treat ischemic eye disease. Objective: To investigate the therapeutic effect of Tongmai fuming decoction combined with anti-VEGF therapy on neovascular ophthalmopathy. Methods: 52 patients (62 eyes) with neovascular ophthalmopathy who met the inclusion criteria from January 2018 to July 2020 were randomly divided into the control and observation groups. The control group was given an intravitreal injection of antivascular endothelial growth factor (VEGF) drugs once a day combined with on-demand treatment. The observation group was treated with traditional Chinese medicine Tongmai fuming decoction in addition to the treatment of anti-VEGF drugs. The best-corrected visual acuity (BCVA) was examined before and after treatment, and optical coherence tomography angiography (OCTA) was used to examine the mean retinal thickness and neovascularization in the macular area. Patients were followed for one year and the number of anti-VEGF injections was recorded. Results: After treatment, the average thickness of BCVA and macular retina in the two groups significantly improved. The BCVA of the control group was 0.59 ± 0.39 3 months after treatment, and that of the experimental group was 0.42 ± 0.25 3 months after treatment. The average thickness of the macular retina in the control group was 304.8 ± 79.7 3 months after treatment, and that in the experimental group was 267.7 ± 64.6 3 months after treatment; The average number of injections of anti-VEGF therapy in the control group was 2.32 ± 1.15 times, and that in the experimental group was 1.74 ± 0.76 times. There was a significant difference between the two groups. Conclusion: Tongmai fuming decoction and anti-VEGF therapy have a synergistic effect in the treatment of neovascular ophthalmopathy, which can reduce the treatment times of anti-VEGF drugs.
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Dermatomyositis (DM) is a poorly prognostic autoimmune disease the pathogenesis of which is multifactorial and not clearly defined. DM may be influenced by genes, environment, and immunity. The typical manifestations of DM are Gottron rash, heliotrope rash, rash on the shoulders and buttocks, erythema around fingernails, excessive keratosis of the epidermis, mechanic's hands, and interstitial lung disease (ILD), among others. Anti-melanoma differentiation-associated 5 gene (MDA5) antibody has been strongly associated with DM. Furthermore, anti-SSA/Ro52 antibody has been reportedly associated with DM. A 49-year-old woman presented with cough, expectoration, and dyspnea. Relevant examinations revealed elevated levels of muscle enzyme, double-positive anti-MDA5 and anti-SSA/Ro52 antibodies, positive rheumatoid factor, and a high titer of anti-citrullinated protein antibody. DM overlapping rheumatoid arthritis with ILD was confirmed. We suggest the use of glucocorticoids combined with immunosuppressant therapy, supplemented with gastric and liver protection, and recommend the use of intravenous immunoglobulins and rituximab.
Subject(s)
Arthritis, Rheumatoid , Dermatomyositis , Exanthema , Lung Diseases, Interstitial , Melanoma , Female , Humans , Middle Aged , Interferon-Induced Helicase, IFIH1 , Dermatomyositis/complications , Dermatomyositis/diagnosis , Dermatomyositis/drug therapy , Autoantibodies , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Exanthema/complications , Retrospective StudiesABSTRACT
OBJECTIVE: To investigate the possible causative factors of central core disease(CCD), the clinical features of a neonatal case with CCD and five patients in the pedigree line were analyzed for RYR1 gene variant. METHODS: Medical and family history inquiries and detailed clinical examinations were performed in the proband. High-throughput sequencing technology was applied to analyze the gene variant of the proband, and Sanger sequencing was applied to verify the pedigree distribution of the variant. RESULTS: The whole exon sequencing results showed that the proband has a missense variant of c. 14591A>C (p.Tyr4864Ser) in the RYR1 gene which was unreported previously; Sanger sequencing results showed that the father, grandfather, the eldest aunt and second aunt of the proband all carried the same variant. The c.14591 A>C variant of RYR1 gene was predicted to be a likely pathogenic (PM2+PM5+PP1+PP3) according to the American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION: The RYR1 gene c.14591A>C (p.Tyr4864Ser) variant may be the genetic cause of the pedigree and genetic testing helps to clarify the diagnosis. Identification of this variant has enriched the variant spectrum of the RYR1 gene.
Subject(s)
Myopathy, Central Core , Exons , Genetic Testing , Humans , Infant, Newborn , Mutation , Pedigree , Ryanodine Receptor Calcium Release Channel/geneticsABSTRACT
A facile cotton fabric with a built-in TLC-SERS structure was fabricated to demonstrate an integrated TLC separation and SERS identification of mixed dyes. The soft and flexible SERS fabric was firstly fabricated using a simple method in which gold nanoparticles were in-situ synthesized on cotton fabrics by heating. ß-CD was then grafted onto cotton fabric through crosslinking with citric acid in presence of sodium hypophosphite monohydrate via esterification reaction. The adsorption and TLC development performance of ß-CD grafted fabrics were comprehensively investigated with two organic dyes, one anionic dye and one nonionic dye. Besides, the recyclable adsorption and separation performance were tested to evaluate its sustainable application prospects. It displayed less adsorption capacity loss and reusable separation performance after several cycles than the pristine cotton fabrics. Finally, two sets of mixed dyes were successfully separated on the TLC fabrics and then identified via on-site SERS according to their different migration distance. The developed TLC-SERS fabric shows the advantage of quick, easy to handle, low-cost, sensitive, and could be exploited in on-site study of synthetic dyes in art objects, textile and packaging products or forensic applications.
Subject(s)
Coloring Agents , Metal Nanoparticles , Adsorption , Gold , Metal Nanoparticles/chemistry , TextilesABSTRACT
INTRODUCTION: Although pulsed dye laser (PDL) remains the gold standard for the treatment of port-wine stains (PWS), hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) is another treatment modality that has been shown to be effective in the treatment of PWS. This study aimed to observe the clinical efficacy and therapeutic response of HMME-PDT in the treatment of pediatric Chinese patients with PWS and to analyze the association between the efficacy of therapy and the dermoscopic features of PWS. METHODS: Pediatric patients with PWS and negative HMME skin test were enrolled between December 2017 and May 2021. Patients received an intravenous injection of 5 mg/kg HMME, and lesions were irradiated with 532-nm LED green light with a power density of 70-80 mW/cm2 for 20-25 min. Digital photographs and dermoscopic images were taken before and after two treatment sessions, and the clinical response was observed. The relationship between the efficacy of HMME-PDT and the dermoscopic features of PWS was retrospectively analyzed. RESULTS: A total of 216 pediatric patients (1-14 years) were recruited. Sixty-six patients had the pink type, while 150 had the purple type. After two HMME-PDT sessions, 55 patients showed excellent efficacy (25.46%), 77 patients showed good efficacy (35.65%), 69 patients showed fair efficacy (31.94%), and 15 patients showed no improvement (6.95%). Dotted and globular vessels were highly associated with excellent efficacy (41.82%); linear vessels were mainly associated with good efficacy (54.55%); reticular vessels were mainly associated with fair (55.07%) and mixed vessels were mainly associated with no improvement (26.66%). CONCLUSION: HMME-PDT is an effective and safe treatment for pediatric patients with PWS. Dotted and globular vessels as well as linear vessels showed better efficacy compared to the other dermoscopic patterns in patients with PWS. Dermoscopy can provide useful clinical information about treatment outcomes.