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BACKGROUND: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) with poor treatment outcomes. The role and underlying mechanisms of ferroptosis in LN remain largely unknown. We aimed to explore ferroptosis-related molecular subtypes and assess their prognostic value in LN patients. METHODS: Molecular subtypes were classified on the basis of differentially expressed ferroptosis-related genes (FRGs) via the Consensus ClusterPlus package. The enriched functions and pathways, immune infiltrating levels, immune scores, and immune checkpoints were compared between the subgroups. A scoring algorithm based on the subtype-specific feature genes identified by artificial neural network machine learning, referred to as the NeuraLN, was established, and its immunological features, clinical value, and predictive value were evaluated in patients with LN. Finally, immunohistochemical analysis was performed to validate the expression and role of feature genes in glomerular tissues from LN patients and controls. RESULTS: A total of 10 differentially expressed FRGs were identified, most of which showed significant correlation. Based on the 10 FRGs, LN patients were classified into two ferroptosis subtypes, which exhibited significant differences in immune cell abundances, immune scores, and immune checkpoint expression. A NeuraLN-related protective model was established based on nine subtype-specific genes, and it exhibited a robustly predictive value in LN. The nomogram and calibration curves demonstrated the clinical benefits of the protective model. The high-NeuraLN group was closely associated with immune activation. Clinical specimens demonstrated the alterations of ALB, BHMT, GAMT, GSTA1, and HAO2 were in accordance with bioinformatics analysis results, GSTA1 and BHMT were negatively correlated with the severity of LN. CONCLUSION: The classification of ferroptosis subtypes and the establishment of a protective model may form a foundation for the personalized treatment of LN patients.
Subject(s)
Ferroptosis , Lupus Nephritis , Neural Networks, Computer , Humans , Ferroptosis/genetics , Ferroptosis/immunology , Lupus Nephritis/immunology , Lupus Nephritis/genetics , Female , Male , Adult , Machine Learning , Prognosis , Middle AgedABSTRACT
Objective: Systemic lupus erythematosus (SLE) is a disease characterised by immune inflammation and damage to multiple organs. Recent investigations have linked competing endogenous RNAs (ceRNAs) to lupus. However, the exact mechanism through which the ceRNAs network affects SLE is still unclear. This study aims to investigate the regulatory functions of the ceRNAs network, which are important pathways that control the pathophysiological processes of SLE. Methods: CircRNA microarray for our tested assays were derived from bone marrow samples from three healthy individuals and three SLE patients in our hospital. The other sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Using the limma package of R program, the differential expression of mRNA and miRNA in the GEO database was discovered. Then predicted miRNA-mRNA and circRNA-miRNA were established using miRMap, miRanda, miRDB, TargetScan, and miTarBase. CircRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, and hub genes were screened using a protein-protein interaction network. Immune infiltration analysis of the hub gene was also performed by CIBERSORT and GSEA. Results: 230 overlapped circRNAs, 86 DEmiRNAs and 2083 DEmRNAs were identified in SLE patients as compared to healthy controls. We constructed a circRNA-miRNA-mRNA ceRNAs network contained 11 overlapped circRNAs, 9 miRNAs and 51 mRNAs. ESR1 and SIRT1 were the most frequently associated protein-protein interactions in the PPI network. KEGG analysis showed that DEGs was enriched in FoxO signaling pathway as well as lipids and atherosclerosis. We constructed a novel circRNA-miRNA-mRNA ceRNA network (HSA circ 0000345- HSA miR-22-3-P-ESR1/SIRT1) that may have a major impact on SLE. Conclusion: Through this bioinformatics and integrated analysis, we suggest a regulatory role for ceRNA network in the pathogenesis and treatment of SLE.
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Tryptophan (TRP) and its indole metabolites exhibit numerous biological effects, especially their antioxidant properties. This study used untargeted metabolomics in conjunction with targeted metabolomics to investigate the differential expression of tryptophan and its indole metabolites in follicular fluid (FF) of diminished ovarian reserve (DOR) and normal ovarian reserve (NOR) populations. This study included patients with DOR (n = 50) and females with NOR (n = 35) who received in vitro fertilization and embryo transfer. Untargeted metabolomics suggests that diminished ovarian reserve affects the metabolic profile of FF, TRP and indole metabolites were significantly down-regulated in the DOR group. Targeted metabolomics quantification revealed that the levels of TRP, IPA and IAA in the FF of the DOR group were significantly lower than those of the NOR group (P < 0.01). The concentration of TRP in FF is positively correlated with the available embryo rate in NOR females. These results provide data support to explore the pathogenesis of DOR and to look for new biomarkers and ovarian protectors. Additionally, alterations in TRP and its indole metabolites in FF may indirectly reflect the interaction between intestinal flora and the follicular microenvironment.
Subject(s)
Ovarian Diseases , Ovarian Reserve , Humans , Female , Follicular Fluid/metabolism , Tryptophan/metabolism , Ovarian Diseases/metabolism , Fertilization in VitroABSTRACT
Objective: To identify the correlation between finger-to-floor distance(FFD) and the spinal function indices and disease activity scores of ankylosing spondylitis (AS) via a multicentre case-control study, and to calculate the optimal cutoff value of FFD using statistical methods. Methods: Patients with AS and healthy individuals were recruited, and the FFD and other spinal mobility values were measured. The correlation between the FFD and the Bath Ankylosing Spondylitis Metric Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) was analyzed using Spearman rank correlation analysis. Receiver operating characteristic (ROC) curves of FFD stratified by gender and age were drawn and their optimal cutoff values were determined. Results: A total of 246 patients with AS and 246 healthy subjects were recruited. The FFD was strongly correlated with BASMI (r = 0.72, p < 0.001), moderately correlated with BASFI (r = 0.50, p < 0.001) and weakly correlated with BASDAI (r = 0.36, p < 0.001). The lowest cutoff value of the FFD was 2.6 cm while the highest was 18.4 cm. Moreover, the FFD was significantly correlated with sex and age. Conclusion: There exists a strong correlation between the FFD and spinal mobility, a moderately correlation and function, which provides reliable data for the evaluation of patients with AS in clinical settings and the rapid screening of low back pain-related diseases in the general population. Furthermore, these findings have clinical potential in improving the missed diagnosis or delayed diagnosis of low back pain.
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INTRODUCTION: 54% of patients with moderate-to-severe knee osteoarthritis (KOA) still reported persistent pain and functional loss after conservative treatment according to guidelines. As an emerging treatment, platelet-rich plasma (PRP) has been proven to significantly relieve pain and improve activity function in patients with mild-to-moderate KOA, either used alone or in combination with hyaluronic acid (HA). However, it is still unclear of its efficacy in moderate-to-severe KOA. This study aims to evaluate the clinical efficacy of PRP and the combination therapy of PRP and HA in patients with moderate-to-severe KOA and to explore the potential synergistic effect of PRP and HA. METHODS AND ANALYSIS: This triple-blind randomised controlled trial will involve a total of 162 participants with moderate-to-severe KOA from two study centres. Participants will be allocated randomly into three groups: the HA group, the PRP group and the combination (PRP+HA) group and, respectively, receive HA (2.5 mL)+saline (3 mL)/PRP (3 mL)+saline (2.5 mL)/PRP (3 mL)+HA (2.5 mL) intra-articular injection each week for 4 consecutive weeks. All of the injections will be performed under the guidance of ultrasound. The primary outcome is the change of Western Ontario and McMaster Universities Osteoarthritis Index from baseline to 6 months, and secondary outcomes include the change of ultrasound images (suprapatellar bursa effusion and synovitis), Timed Up and Go test and 12-Item Short-Form Health Survey. All outcomes will be evaluated at baseline and 1-month, 3-month and 6-month follow-ups. Data will be analysed on intention-to-treat principles and a per-protocol basis. ETHICS AND DISSEMINATION: This protocol was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University (reference number (2021)-02-231-02). The study results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2100050974.
Subject(s)
Osteoarthritis, Knee , Platelet-Rich Plasma , Humans , Osteoarthritis, Knee/therapy , Osteoarthritis, Knee/drug therapy , Hyaluronic Acid/therapeutic use , Postural Balance , Time and Motion Studies , Pain/drug therapy , Injections, Intra-Articular , Treatment Outcome , Randomized Controlled Trials as TopicABSTRACT
Mitochondrial alternative oxidase 1a (AOX1a) plays an extremely important role in the critical node of seed viability during storage. However, the regulatory mechanism is still poorly understood. The aim of this study was to identify the regulatory mechanisms by comparing OsAOX1a-RNAi and wild-type (WT) rice seed during artificial aging treatment. Weight gain and time for the seed germination percentage decreased to 50% (P50) in OsAOX1a-RNAi rice seed, indicating possible impairment in seed development and storability. Compared to WT seeds at 100%, 90%, 80%, and 70% germination, the NADH- and succinate-dependent O2 consumption, the activity of mitochondrial malate dehydrogenase, and ATP contents all decreased in the OsAOX1a-RNAi seeds, indicating that mitochondrial status in the OsAOX1a-RNAi seeds after imbibition was weaker than in the WT seeds. In addition, the reduction in the abundance of Complex I subunits showed that the capacity of the mitochondrial electron transfer chain was significantly inhibited in the OsAOX1a-RNAi seeds at the critical node of seed viability. The results indicate that ATP production was impaired in the OsAOX1a-RNAi seeds during aging. Therefore, we conclude that mitochondrial metabolism and alternative pathways were severely inhibited in the OsAOX1a-RNAi seeds at critical node of viability, which could accelerate the collapse of seed viability. The precise regulatory mechanism of the alternative pathway at the critical node of viability needs to be further analyzed. This finding might provide the basis for developing monitoring and warning indicators when seed viability declines to the critical node during storage.
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PURPOSE: To examine the short-term complications of arterial cannulation for intraoperative monitoring and their related risk factors. METHODS: We included adult inpatients (≥ 18 years old) who underwent an initial transradial access (TRA) cannulation and were scheduled for general surgery between April 8 and November 30, 2020. We used 20G arterial puncture needles for puncturing and manual compression for hemostasis. Demographic, clinical, surgical, anesthetic, and laboratory data were extracted from electronic medical records. Vascular, neurologic, and infectious complications of TRA cannulation were recorded and analyzed. Logistic regression analyses were used to identify risk factors related to TRA cannulation for intraoperative monitoring. RESULTS: Among 509 included patients, 174 developed TRA cannulation-related complications. Puncture site bleeding/hematoma and median nerve injury were observed in 158 (31.0%) and 16 (3.1%) patients, respectively. No patient developed cannula-related infections. Logistic regression analysis revealed increased odds of puncture site bleeding/hematoma in women (odds ratio 4.49, 95% CI 2.73-7.36; P < 0.001) and patients who received intraoperative red blood cell (RBC) suspension transfusion ≥ 4U (odds ratio 5.26, 95% CI 1.41-19.57; P = 0.01). No risk factors for nerve injury were identified. CONCLUSION: Bleeding/hematoma were a common complication of TRA cannulation for intraoperative hemodynamic monitoring during general surgery. Median nerve injury may be an under recognized complication. Female sex and extensive intraoperative RBC transfusion are associated with an increased risk of bleeding/hematoma; however, the risk factors for nerve injury remain unclear. TRIAL REGISTRATION: The study protocol was registered at https://www.chictr.org.cn (ChiCTR1900025140).
Subject(s)
Hemodynamic Monitoring , Adult , Female , Humans , Adolescent , Cannula , Hematoma , Punctures , CatheterizationABSTRACT
BACKGROUND: The relationship between transforming growth factor-ß1 (TGF- ß1) gene polymorphisms and systemic lupus erythematosus (SLE) has been reported in many studies, but there were still controversies with regard to their conclusions. METHODS: Relevant documents were retrieved from 5 electronic databases such as PubMed, Embase, Cochrane Library, Wanfang, and China national knowledge infrastructure. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the relationship between TGF-ß1 genetic variation and SLE. RESULTS: The present meta-analysis included 12 case-control studies with 1308 SLE patients and 1714 healthy controls. The results of the combined analyses showed that TGF-ß1 C509T polymorphism showed no association with SLE risk (TC vs CC: OR = 1.16, 95% CI = 0.91-1.48, PHeterogeneity (PH) = 0.579; TT vs CC: OR = 1.15, 95% CI = 0.63-2.09, PH = 0.003; T vs C: OR = 1.08, 95% CI = 0.8-1.45, PH = 0.003; TC/TT vs CC: OR = 1.17, 95% CI = 0.93-1.46, PH = 0.133; and TT vs TC/CC: OR = 1.06, 95% CI = 0.64-1.76, PH = 0.004). TGF-ß1 G915C and T869C polymorphisms were not linked with SLE risk. Moreover, subgroup analysis stratified by ethnicity and Hardy-Weinberg equilibrium revealed no significant correlation of TGF-ß1 T869C, C509T, G915C polymorphisms with SLE risk. CONCLUSION: TGF-ß1 T869C, C509T, G915C polymorphisms might not be associated with the development of SLE.
Subject(s)
Lupus Erythematosus, Systemic , Transforming Growth Factor beta1 , Humans , Case-Control Studies , Ethnicity , Genetic Predisposition to Disease , Genotype , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide , Transforming Growth Factor beta1/geneticsABSTRACT
This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.
Subject(s)
Neuralgia , Sciatic Neuropathy , Rats , Animals , Rats, Sprague-Dawley , Neuroinflammatory Diseases , Constriction , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Sciatic Nerve/injuries , Analgesics/pharmacology , Sciatic Neuropathy/drug therapy , Sciatic Neuropathy/metabolism , Neuralgia/drug therapy , Neuralgia/metabolism , HyperalgesiaABSTRACT
Chronic muscle inflammation exacerbates the pathogenesis of Duchenne muscular dystrophy (DMD), which is characterized by progressive muscle degeneration and weakness. NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome plays a key role in the inflammatory process, and its abnormal activation leads to a variety of inflammatory or immune diseases. TRIM72 (MG53) is a protective myokine for tissue repair and regeneration. However, little is known about the potential impact of TRIM72 in the crosstalk between mitophagy and inflammatory process of DMD. Here, 10-week-old male mdx mice were injected intramuscularly with adeno-associated virus (AAV-TRIM72) to overexpress TRIM72 protein for 6 weeks. Then, skeletal muscle samples were collected, and relevant parameters were measured by histopathological analysis and molecular biology techniques. C2C12 cell line was transfected with lentivirus (LV-TRIM72) to overexpress or siRNA (si-TRIM72) to suppress the TRIM72 expression for the following experiment. Our data firstly showed that the TRIM72 expression was decreased in skeletal muscles of mdx mice. Then, we observed the increased NLRP3 inflammasome and impaired mitophagy in mdx mice compared with wild type mice. In mdx mice, administration of AAV-TRIM72 alleviated the accumulation of NLRP3 inflammasome and the consequent IL-18 and IL1ß maturation by inducing autophagy, while this protective effect was reversed by chloroquine. Mitochondrial reactive oxygen species (mtROS), as a recognized activator for NLRP3 inflammasome, was attenuated by TRIM72 through the induction of mitophagy in C2C12 cells. Additionally, we proposed that the TRIM72 overexpression might promote mitophagy through both the early stage by PI3K-AKT pathway and the late stage by autolysosome fusion. In conclusion, the current study suggests that TRIM72 prevents DMD inflammation via decreasing NLRP3 inflammasomes and enhancing mitophagy. Collectively, our study provides insight into TRIM72 as a promising target for therapeutic intervention for DMD.
Subject(s)
Inflammasomes , Membrane Proteins , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Male , Mice , Inflammasomes/metabolism , Inflammation , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice, Inbred mdx , Mitophagy , Muscle, Skeletal/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Phosphatidylinositol 3-KinasesABSTRACT
BACKGROUND: Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. METHODS: GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher's exact test). DISCUSSION: GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk-benefit profile of this treatment in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT05291650. Registered on 23 March 2022.
Subject(s)
Osteoarthritis, Knee , Synovitis , Humans , Osteoarthritis, Knee/therapy , Glucocorticoids/adverse effects , Quality of Life , Pain/drug therapy , Injections, Intra-Articular , Synovitis/diagnostic imaging , Synovitis/drug therapy , Synovitis/complications , Inflammation/drug therapy , Adipose Tissue , Treatment Outcome , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
AIMS: We aimed to determine the effects of different exercise modalities in patients with type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, Embase, and the Cochrane Library from their inception until July 2020 to identify randomised controlled trials (RCTs) on exercise in adults with T2DM. Paired reviewers independently performed study selection, data extraction, and risk of bias assessment. The certainty of the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. RESULTS: A total of 106 RCTs that enroled eight exercise modalities with 7438 patients were included. Six exercise modalities, except unsupervised aerobic/resistance exercise, significantly reduced glycosylated haemoglobin (HbA1c), with mean differences (MDs) ranging from 0.71 (95% confidence interval [CI]: 0.34-1.08) to 0.34 (95% CI: 0.17-0.52), low to high certainty, in comparison with no exercise. The evidence of low to moderate certainty showed that supervised aerobic/resistance exercise improved glycaemic control, body weight, blood pressure, and blood lipid profiles compared with no exercise. Flexibility exercise may be associated with glycaemic control (HbA1c: MD = 0.71, 95% CI: 0.34-1.08); fasting plasma glucose (MD = 1.48, 95% CI: 0.78-2.17), and weight loss (MD = 1.80, 95% CI: 0.85-2.75) compared with controls, but not blood pressure and lipid profiles. Balance exercise showed the largest benefit in improving total cholesterol (MD = 52.81, 95% CI: 28.47-77.16) and low certainty. We found no significant differences between exercises and the triacylglycerol (TG) level. CONCLUSIONS: Overall, our network meta-analyses support the recommendation for exercise in patients with T2DM, especially supervised exercises. Limited evidence supports the benefits of flexibility and balance exercises. The effectiveness of exercise modalities for TG reduction remains unclear.
Subject(s)
Diabetes Mellitus, Type 2 , Adult , Humans , Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin , Lipids , Network Meta-Analysis , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: The aim of this systematic review and meta-analysis was to analyze the reproductive outcomes of natural pregnancy after hysteroscopic septum resection in patients with recurrent miscarriage, primary infertility, or secondary infertility. DATA SOURCES: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Database, and Chinese Biomedical Literature Database (CBM) databases were electronically searched. The search time frame was from inception up to July 2021. The English search terms were (arcuate* and uter*), (sept* and uter*), (subseptate* and uter*), metroplast*, septoplast*, and resect*. STUDY ELIGIBILITY CRITERIA: Selection criteria included randomized controlled trials, cohort studies, and case series that explored reproductive outcomes after hysteroscopic septum resection in patients with recurrent miscarriage, primary infertility, or secondary infertility with or without a control group. METHODS: The primary outcomes were the live birth rate and eventual postoperative live birth rate after hysteroscopic septum resection. The secondary outcomes were the clinical pregnancy rate, preterm birth rate, and miscarriage rate. Study-level proportions of outcomes were transformed using the Freeman-Tukey double-arcsine transformation to calculate pooled values for the postoperative rates; the counted data were analyzed using relative risk as the effect analysis statistic, and each effect size was provided with its 95% confidence interval. Heterogeneity between the results of the included studies was analyzed using the I2 test. RESULTS: Overall, 5 cohort studies and 22 case series involving 1506 patients were included. In patients with a septate uterus and recurrent miscarriage, hysteroscopic septum resection was associated with an increased live birth rate (relative risk, 1.77; 95% confidence interval, 1.26-2.49; P=.001; I2=0%), resulting in a postoperative live birth rate of 66% (95% confidence interval, 59-72), and septum resection was associated with a reduced preterm birth rate (relative risk, 0.15; 95% confidence interval, 0.04-0.53; P=.003; I2=0%) and miscarriage rate (relative risk, 0.36; 95% confidence interval, 0.20-0.66; P=.0009; I2=0%). In patients with a septate uterus and primary infertility, hysteroscopic septum resection was associated with an increased live birth rate (relative risk, 4.12; 95% confidence interval, 1.19-14.29; P=.03; I2=0%) and clinical pregnancy rate (relative risk, 2.28; 95% confidence interval, 1.04-4.98; P=.04; I2=0%). The postoperative live birth rate was 37% (95% confidence interval, 30-44), and the miscarriage rate of patients with primary infertility was reduced (relative risk, 0.19; 95% confidence interval, 0.06-0.56; P=.003). The efficacy of hysteroscopic septum resection in patients with secondary infertility was unclear. However, their postoperative live birth rate was found to be 41% (95% confidence interval, 2-88). CONCLUSION: Hysteroscopic septum resection is associated with an increased live birth rate and a reduced miscarriage rate in patients with recurrent miscarriage or primary infertility, indicating that septum resection may improve the reproductive outcomes of these patients. The effectiveness of septum resection was unclear for patients with secondary infertility. These findings are limited by the quality of the included studies, warranting further randomized controlled trials, including only patients with recurrent miscarriage or primary infertility.
Subject(s)
Abortion, Habitual , Infertility , Premature Birth , Septate Uterus , Infant, Newborn , Pregnancy , Female , Humans , Hysteroscopy , Premature Birth/epidemiology , Premature Birth/etiology , Premature Birth/surgery , Infertility/surgery , Abortion, Habitual/diagnosis , Abortion, Habitual/epidemiology , Abortion, Habitual/etiologyABSTRACT
OBJECTIVES: Recommendations from clinical practice guidelines (CPGs) for individuals with type 2 diabetes mellitus (T2DM) may be inconsistent, and little is known about their quality. Our aim in this study was to systematically review the consistency of globally available CPGs containing nutritional recommendations for T2DM and to assess the quality of their methodology and reporting. METHODS: PubMed, China Biology Medicine and 4 main guideline websites were searched. Four researchers independently assessed quality of the methodology and reporting using the Appraisal of Guidelines for Research and Evaluation, second edition (AGREE II) instrument and the Reporting Items for Practice Guidelines in HealThcare (RIGHT) checklist. RESULTS: Fifteen CPGs include 65 nutritional recommendations with 6 sections: 1) body weight and energy balance; 2) dietary eating patterns; 3) macronutrients; 4) micronutrients and supplements; 5) alcohol; and 6) specific, functional foods. Current nutritional recommendations for individuals with T2DM on specific elements and amounts are not completely consistent in different CPGs and fail to assign the specific supporting evidence and strength of recommendations. To use nutritional recommendations to guide and manage individuals with T2DM, it is important to address the current challenges by establishing a solid evidence base and indicating the strength of recommendations. Overall, 8 CPGs classified as recommended for clinical practice used AGREE II. Fifteen CPGs adhere to <60% of RIGHT checklist items. CONCLUSIONS: High-quality evidence is needed to potentially close knowledge gaps and strengthen the recommendation. The AGREE II instrument, along with the RIGHT checklist, should be endorsed and used by CPG developers to ensure higher quality and adequate use of their products.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , ChinaABSTRACT
OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by immune inflammation. It involves multiple organs. Many studies have demonstrated that circRNAs are closely associated with SLE. Nonetheless, the potential mechanism by which circRNAs impacts SLE is not fully understood. The aim of this study was to explore the regulatory roles of circRNAs, the key genes and pathways governing the pathophysiological processes of SLE, and to screen therapeutic agents. METHODS: The sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Candidates were identified to construct a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Gene functional enrichments were performed on the DAVID database. Protein-protein interaction (PPI) network was constructed by STRING database and visualised in Cytoscape software. The hub genes were explored by the MCODE plugin app. The Connectivity Map L1000 platform was used to identify potential agents. RESULTS: A total of 1093 differentially expressed circRNAs (DEcircRNAs), 42 differentially expressed miRNAs (DEmiRNAs) and 1431 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 3 overlapped circRNAs, 13 miRNAs and 352 target mRNAs into a circRNA-miRNA-mRNA network. We next identified 44 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with MAPK signalling pathway. In addition, we discovered several chemicals as potential treatment options for SLE. CONCLUSIONS: Through this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of SLE from the view of a competitive endogenous RNA (ceRNA) network.
Subject(s)
Lupus Erythematosus, Systemic , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Protein Interaction Maps/genetics , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/genetics , Gene Regulatory NetworksABSTRACT
Accurate and rapid segmentation of the hippocampus can help doctors perform intractable temporal lobe epilepsy (TLE) preoperative evaluations to identify good surgical candidates. This study aims to establish a radiomics system for the automatic diagnosis of hippocampal sclerosis with the help of machine learning. A total of 240 cases were analysed to develop a diagnostic model. First, an automatic hippocampal segmentation process was established that exploits a priori knowledge of the relatively fixed location of the hippocampus in brain partitions, as well as a deep-learning segmentation network based on an Attention U-net. Then, we extracted 527 radiomics features from each side of the segmented hippocampus. The iterative sparse representation based on feature selection and a support vector machine classifier were finally used to establish the diagnostic model of hippocampal sclerosis. The diagnostic model consists of two consecutive steps: distinguish hippocampal sclerosis (HS) from normal control (NC) and detect whether the HS is located on the left or right side. When the automatic diagnosis model identified HS and NC, the sensitivity and specificity reached 0.941 and 0.917 in the 10-fold cross-validation set and 0.920 and 0.909 in the independent testing set. When the diagnostic model detected HS lateralization, the sensitivity and specificity reached 0.923 and 0.920 in cross-validation and 0.909 and 0.929 in independent testing. Our results show that the developed radiomics model can help detect TLE patients with hippocampal sclerosis and has the potential to simplify preoperative evaluations and select surgical candidates.
Subject(s)
Deep Learning , Epilepsy, Temporal Lobe , Hippocampal Sclerosis , Humans , Magnetic Resonance Imaging/methods , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/surgery , Hippocampus/diagnostic imagingABSTRACT
Purpose To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery. Methods According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The KaplanMeier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences. Results A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41 months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p < 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p < 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p < 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p < 0.05). Conclusions For patients aged 50 years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups (AU)
Subject(s)
Humans , Female , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Mastectomy, Segmental/methods , Retrospective Studies , Kaplan-Meier Estimate , SEER Program , Radiotherapy, AdjuvantABSTRACT
BACKGROUND: Surgical removal of lesions around the rolandic cortex remains a challenge for neurosurgeons owing to the high risk of neurological deficits. Evaluating the risk factors associated with motor deficits after surgery in this region may help reduce the occurrence of motor deficits. OBJECTIVE: To report our surgical experience in treating epileptic lesions involving the rolandic and perirolandic cortices. METHODS: We performed a single-center retrospective review of patients undergoing epilepsy surgeries with lesions located in the rolandic and perirolandic cortices. Patients with detailed follow-up information were included. The lesion locations, resected regions, and invasive exploration techniques were studied to assess their relationship with postoperative motor deficits. RESULTS: Forty-one patients were included. Twenty-three patients suffered from a transient motor deficit, and 2 had permanent disabilities after surgery. Six patients with lesions at the posterior bank of the precentral sulcus underwent resection, and 5 experienced short-term motor deficits. Two patients with lesions adjacent to the anterior part of the precentral gyrus, in whom the adjacent precentral gyrus was removed, experienced permanent motor deficits. Lesions located at the bottom of the central sulcus and invading the anterior bank of the central sulcus were observed in 3 patients. The patients did not experience permanent motor deficits after surgery. CONCLUSION: The anterior bank of the central sulcus is indispensable for motor function, and destruction of this region would inevitably cause motor deficits. The anterior bank of the precentral gyrus can also be removed without motor impairment if there is a preexisting epileptogenic lesion.
Subject(s)
Epilepsy , Motor Cortex , Epilepsy/surgery , Humans , Postoperative Period , Retrospective StudiesABSTRACT
PURPOSE: To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery. METHODS: According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The Kaplan-Meier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences. RESULTS: A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41 months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p < 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p < 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p < 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p < 0.05). CONCLUSIONS: For patients aged 50 years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups.
Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Female , Humans , Mastectomy, Segmental/methods , Propensity Score , Radiotherapy, Adjuvant , Retrospective StudiesABSTRACT
PURPOSE: Microvascular decompression (MVD) surgery is the only potential curative method for hemifacial spasm (HFS). Little attention is paid to those recurrent/residual HFS cases. We want to study the potential etiology of those recurrent/residual HFS cases and evaluate the value of reoperation. METHODS: We retrospectively reviewed reoperation hemifacial spasm patients in our hospital. Intraoperative videos or images were carefully reviewed, and the etiology of recurrent/residual HFS is roughly divided into three categories. Intraoperative findings, surgical outcomes, and complications were carefully studied to assess the value of reoperation for recurrent/residual HFS patients. RESULTS: A total of 28 cases were included in our case series. Twenty-three of them are recurrent HFS cases, and 5 of them are residual HFS cases. The mean follow-up duration is 24.96 months. There are seventeen patients with missed culprit vessels or insufficient decompression of root exit zone (REZ), eight patients with Teflon adhesion, and three patients with improper application of decompression materials in our case series. The final reoperation outcome with 17 excellent, seven good, and four fair, respectively. Eight (28.57%) of them experienced long-term complications after reoperation. CONCLUSION: Re-operation for recurrent/residual HFS is an effective therapy and can achieve a higher cure rate. However, the complication rate is higher compared to the first MVD surgery. Accurately identifying REZ and proper decompression strategies to deal with the culprit vessels are very important for surgical success. TRIAL REGISTRATION NUMBER: UIN: researchregistry7603. Date of registration: Jan. 31st, 2022 "retrospectively registered".