To investigate the effect of biologic therapy on risk of fracture in selected rheumatic and autoimmune diseases.
The PubMed, Cochrane library, and EMBASE databases were systematically searched from ...the inception dates to June 4, 2021. Randomized clinical trials (RCTs) comparing biological disease-modifying antirheumatic drugs (bDMARDs) with non-bDMARDs or placebo in patients with five selected rheumatic and autoimmune diseases were included. Meta-analyses were conducted to calculate the odds ratio (OR) with 95 % confidence intervals (CIs) for major osteoporotic fracture, hip fracture, osteoporotic non-vertebral fracture, and total fracture.
A total of 100 RCTs involving 51,413 participants fulfilled the inclusion criteria. In patients with psoriasis (Ps), and psoriatic arthritis (PsA), compared with placebo or non-bDMARDs therapy, the risk of major osteoporotic fracture (OR, 0.34 95 %Cl, 0.15–0.76, p = 0.009), hip fracture (OR, 0.22 95 %Cl, 0.05–0.89, p = 0.03), and osteoporotic non-vertebral fracture (OR, 0.26 95 %Cl, 0.10–0.62, p = 0.003) were significantly decreased with the use of bDMARDs. In patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), systemic lupus erythematosus (SLE), and inflammatory bowel diseases (IBD), the risk of fracture were not changed with biologic treatment.
The existing evidence from RCTs indicated the use of bDMARDs was associated with a low risk of major osteoporotic fracture, hip fracture, and osteoporotic non-vertebral fracture in patients with Ps and PsA. There are still urgent needs for studies regarding the actions of biologic therapies on the risk of bone fractures in systemic inflammatory diseases.
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There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and ...meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00–0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04–0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, −0.07units/kg/day, 95% CI, −0.11 to −0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, −0.11units/kg/day, 95% CI, −0.23 to −0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.
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•Immunotherapies were associated with the preservation of 2 h and 4 h C-peptide AUC in patients with T1D.•Immunotherapies tended to reduce the daily insulin dosage in patients with T1D.•Immunotherapies did not increase the risk of hypoglycemia in patients with T1D.•TNF-a inhibitor and T cell-targeted immunotherapy might be promising game changers to delay the development of T1D.
Neoadjuvant immunotherapy has brought new hope for patients with non-small cell lung cancer (NSCLC). However, limited by the lack of clinically feasible markers, it is still difficult to select NSCLC ...patients who respond well and to predict patients’ clinical outcomes before the treatment. Before the treatment, we isolated plasma extracellular vesicles (EVs) from three cohorts (discovery, training and validation) of 78 NSCLC patients treated with neoadjuvant immunotherapy. To identify differentially-expressed EV long RNAs (exLRs), we employed RNA-seq in the discovery cohort. And we subsequently used qRT-PCR to establish and validate the predictive signature in the other two cohorts. We have identified 8 candidate exLRs from 27 top-ranked exLRs differentially expressed between responders and non-responders, and tested their expression with qRT-PCR in the training cohort. We finally identified H3C2 (P = 0.029), MALAT1 (P = 0.043) and RPS3 (P = 0.0086) significantly expressed in responders for establishing the predictive signature. Integrated with PD-L1 expression, our signature performed well in predicting immunotherapeutic responses in the training (AUC=0.892) and validation cohorts (AUC=0.747). Furthermore, our signature was proven to be a predictor for favorable prognosis of patients treated with neoadjuvant immunotherapy, which demonstrates the feasibility of our signature in clinical practices (P = 0.048). Our results demonstrate that the exLR-based signature could accurately predict responses to neoadjuvant immunotherapy and prognosis in NSCLC patients.
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Objective
This study aimed to investigate the clinical application effect of an augmented reality (AR) plasticity model on the postoperative visual function recovery of children with concomitant ...exotropia.
Methods
Between September 2019 and October 2021, 28 patients with concomitant exotropia who visited Shenzhen Children’s Hospital (9 male and 19 female) were enrolled in this study. The average age of the patients was 6.4 ± 1.8 years. Postoperative rehabilitation training was conducted using a personalized AR binocular visual perception plasticity model developed based on the patient’s examination results. After 1 month, 3 months, and 6 months of training, the patients returned to the hospital for examinations of perceptual eye position, static zero-order stereopsis, dynamic first-order fine stereopsis, and dynamic second-order coarse stereopsis to compare the changes in eye position control and stereovision function.
Results
After 6 months of eye position training, the horizontal perception eye position of the 28 patients was significantly lower than that before training. The difference in eye position at the first and third months compared with that before training was not statistically significant (1st month: z = −2.255,
p
= 0.024 > 0.017; 3rd month: z = −2.277,
p
= 0.023 > 0.017; 6th month: z = −3.051,
p
= 0.002 < 0.017). The difference in vertical perceptual eye position after training compared with that before training was not statistically significant (1st month: z = −0.252, p = 0.801 > 0.017; 3rd month: z = −1.189, p = 0.234 > 0.017; 6th month: z = −2.225,
p
= 0.026 > 0.017). The difference in 0.8-m static zero-order stereopsis before and after training was not statistically significant (1st month: z = −2.111, p = 0.035 > 0.017; 3rd month: z = −1.097,
p
= 0.273 > 0.017; 6th month: z = −1.653,
p
= 0.098 > 0.017). The 1.5-m static zero-order stereopsis was improved after 1 month, 3 months, and 6 months of training compared with that before training (1st month: z = −3.134,
p
= 0.002 < 0.017; 3rd month: z = −2.835,
p
= 0.005 < 0.017; 6th month: z = −3.096,
p
= 0.002 < 0.017). Dynamic first-order fine stereopsis and dynamic second-order coarse stereopsis were measured in the 28 patients before and after training. Patients 1 and 18 had no dynamic first-order fine stereopsis before training, but both regained dynamic stereopsis after 1 month, 3 months, and 6 months of training. Patient 16 had no dynamic first-order fine stereopsis or dynamic second-order coarse stereopsis before training, but first-order and second-order stereopsis had been reconstructed after 1 month, 3 months, and 6 months of training.
Conclusion
Concomitant exotropia surgery improved the basic problem of eye position at the ocular muscle level, but the patient’s perceptual eye position and visual function defects at the brain visual level remained. This might partly explain the poor postoperative clinical effect. The AR plasticity model can improve patients’ horizontal perceptual eye position and multi-dimensional stereoscopic function, and its clinical effect warrants further study.
Three new phenolic compounds, epicocconigrones C-D (
-
) and flavimycin C (
), together with six known phenolic compounds: epicocconigrone A (
); ...2-(10-formyl-11,13-dihydroxy-12-methoxy-14-methyl)-6,7-dihydroxy-5-methyl-4-benzofurancarboxaldehyde (
); epicoccolide B (
); eleganketal A (
); 1,3-dihydro-5-methoxy-7-methylisobenzofuran (
); and 2,3,4-trihydroxy-6-(hydroxymethyl)-5-methylbenzyl-alcohol (
), were isolated from fermentation cultures of a deep-sea sediment-derived fungus,
. Their planar structures were elucidated based on the 1D and 2D NMR spectra and HRESIMS data. The absolute configurations of compounds
-
were determined by ECD calculations. Compound
represented a rare fully symmetrical isobenzofuran dimer. All compounds were evaluated for their
-glucosidase inhibitory activity, and compounds
,
-
, and
exhibited more potent
-glucosidase inhibitory effect with IC
values ranging from 17.04 to 292.47 μM than positive control acarbose with IC
value of 822.97 μM, indicating that these phenolic compounds could be promising lead compounds of new hypoglycemic drugs.
Recent research has shown that ferroptosis, the iron-dependent accumulation of lipid peroxides that leads to cell death, suppresses cancer metastasis. However, the role of ferroptosis in prostate ...cancer metastasis has not been completely elucidated. In the current study, we identified the essential role of serum/glucocorticoid regulated kinase 2 (SGK2) in promoting prostate cancer metastasis by inhibiting ferroptosis. We found that the expression of SGK2 was higher in metastatic prostate cancer and predicted poor clinical outcomes. SGK2 knockdown inhibited the metastatic capacity of prostate cancer cells in vivo and in vitro, while SGK2 overexpression inhibited ferroptosis and facilitated prostate cancer metastasis by phosphorylating the Thr-24 and Ser-319 sites of forkhead box O1 (FOXO1). This process induced the translocation of FOXO1 from the nucleus to the cytoplasm, relieving the inhibitory effect of FOXO1 on glutathione peroxidase 4 (GPX4). These findings delineated a novel role of SGK2 in ferroptosis regulation of prostate cancer metastasis, identifying a new key pathway driving prostate cancer metastasis and potentially providing new treatment strategies for metastatic prostate cancer.
Pesticides play a crucial role in agricultural production by preventing diseases and pests and ensuring food yield. However, the irrational use of pesticides can lead to numerous issues that ...compromise crop quality and counteract the original intentions of their application. Therefore, it is necessary to identify more effective methods to counteract pesticide stress. Here we review the impacts of herbicides, insecticides, and fungicides on plants and the measures taken to reduce pesticide residues on plants. We have found that despite the substantial differences in the mechanisms of action of the aforementioned three types of pesticides, the adverse effects they inflict on plants are similar, and at certain dosages, they can severely constrain plant growth and disrupt physiological functions. Also, most current research on using exogenous growth regulators to alleviate pesticide stress still focuses on photosynthesis, the antioxidant system, three-stage detoxification, and secondary metabolites, neglecting the search for genes that respond to pesticide stress. We believe that by combining biological protection with post-harvest treatment techniques and exploring potential genes that are responsive to pesticide stress, a better strategy for dealing with pesticide stress can be found, thereby promoting sustainable agricultural development.
To exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors.
Pubmed, Medline, ...Embase, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used.
The numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05). Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation (β = - 0.461, 95% CI - 0.726 to - 0.197), PAD (β = - 0.359, 95% CI - 0.545 to - 0.172) and DF (β = - 0.476, 95% CI - 0.836 to - 0.116). Lower baseline diastolic blood pressure (β = - 0.528, 95% CI - 0.852 to - 0.205), more systolic blood pressure reduction (β = - 0.207, 95% CI - 0.390 to - 0.023) and more diastolic blood pressure reduction (β = - 0.312, 95% CI - 0.610 to - 0.015) were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment.
The risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment.
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