Comparative efficacy of five approved Janus kinase inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis: a systematic review and network meta-analysis of randomized controlled trials

BackgroundThe European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are insensitive or under-responsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). But there was no recommendation for which one was preferred in five currently approved JAK inhibitors. The objective of this network meta-analysis study was to evaluate the efficacy of five JAK inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis.MethodsThe randomized controlled trials (RCTs) of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy or combined with csDMARD in the treatment of active RA were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to December 2023. The control group included placebo or csDMARD. Outcome indicators included American College of Rheumatology 20% response (ACR20), ACR50, ACR70 and the percentage of patients achieving 28-joint disease activity score using C-reactive protein (DAS28(CRP))<2.6 at 12 weeks and 24 weeks. The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95%CI) as effect sizes to analyze the statistics.ResultsThis study included thirty-six RCTs with 16,713 patients. All JAK inhibitors were more effective than placebo in ACR20 (RRs ranging between 1.74 and 3.08), ACR50 (RRs ranging between 2.02 and 7.47), ACR70 (RRs ranging between 2.68 and 18.13), DAS28(CRP) < 2.6 (RRs ranging between 2.70 and 7.09) at 12 weeks. Upadacitinib 30 mg and upadacitinib 15 mg showed relatively good efficacy according to their relative SUCRA ranking. All JAK inhibitors were more effective than csDMARD or placebo in ACR20 (RRs ranging between 1.16 and 1.86), ACR50 (RRs ranging between 1.69 and 2.84), ACR70 (RRs ranging between 1.50 and 4.47), DAS28(CRP) < 2.6 (RRs ranging between 2.28 and 7.56) at 24 weeks. Upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD showed relatively good efficacy according to their relative SUCRA ranking. The safety analysis results such as serious infection, malignancy, major adverse cardiovascular event (MACE), and venous thromboembolic events (VTE) showed no statistical difference.ConclusionThis NMA study indicated that all JAK inhibitors performed better than placebo. Based on the results of this study, upadacitinib 30 mg, upadacitinib 15 mg, upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD were recommended treatment options with relatively good efficacy and safety. However, attention should be paid to monitoring the occurrence of adverse events in high-risk RA patients with medication. Combination therapy with csDMARD might be more suitable for the maintenance of long-term efficacy. However, in clinical practice, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation

Perioperative Outcomes of Using Different Temperature Management Strategies on Pediatric Patients Undergoing Aortic Arch Surgery: A Single-Center, 8-Year Study

Background: With the widespread application of regional low-flow perfusion (RLFP), development of surgical techniques, and shortened circulatory arrest time, deep hypothermia is indispensable for organ protection. Clinicians have begun to increase the temperature to reduce hypothermia-related adverse outcomes. The aim of this study was to evaluate the safety and efficacy of elevated temperatures during aortic arch surgery with lower body circulatory arrest (LBCA) combined with RLFP.Methods: We retrospectively analyzed data from 207 consecutive pediatric patients who underwent aortic arch repair with LBCA & RLFP between January 2010 and July 2017 and evaluated different hypothermia management strategies. The overall cohort was divided into three groups: deep hypothermia (DH, 20.0–25.0°C), moderate hypothermia (MoH, 25.1–30.0°C) and mild hypothermia (MH, 30.1–34.0°C).Results: The percentage of AKI-1 occurrences was significantly increased in the MH group (51.52%) compared to those in the DH (25.40%) and MoH (37.84%) groups (P = 0.036); prolonged hospital stay occurrences were decreased with elevated temperature (DH 47.62%, MoH 28.83%, MH 18.18%, P = 0.006). Neurological complications, peritoneal dialysis, hepatic dysfunction, 30-day hospital mortality, delay extubation occurrences were no significant among the groups. Logistic analysis showed that the MH group was negatively associated with post-op AKI-1 compared with the DH group [OR = 0.329 (0.137–0.788), P = 0.013], no differences were found between the MoH and the MH group. Compared to other groups, the intubation time (P = 0.006) and postoperative hospital stay (P = 0.009) were significantly decreased in the MH group. Multivariate logistic analysis showed hypothermia levels were not significant with prolonged hospital stay.Conclusions: This retrospective analysis demonstrated that for pediatric patients undergoing surgeries with RLFP & LBCA, three different gradient temperature management strategies are available: deep, moderate, and mild hypothermia. Utilizing mild or moderate hypothermia is safe and feasible. Although the number of AKI-1 occurrences in the MH group was significantly increased compared to those in the other groups, further analysis showed no significance in the MoH and MH group, mild hypothermia management is as safe as others when used appropriately

Development of a Hybrid Atomic Force Microscopic Measurement System Combined with White Light Scanning Interferometry

A hybrid atomic force microscopic (AFM) measurement system combined with white light scanning interferometry for micro/nanometer dimensional measurement is developed. The system is based on a high precision large-range positioning platform with nanometer accuracy on which a white light scanning interferometric module and an AFM head are built. A compact AFM head is developed using a self-sensing tuning fork probe. The head need no external optical sensors to detect the deflection of the cantilever, which saves room on the head, and it can be directly fixed under an optical microscopic interferometric system. To enhance the system’s dynamic response, the frequency modulation (FM) mode is adopted for the AFM head. The measuring data can be traceable through three laser interferometers in the system. The lateral scanning range can reach 25 mm × 25 mm by using a large-range positioning platform. A hybrid method combining AFM and white light scanning interferometry is proposed to improve the AFM measurement efficiency. In this method, the sample is measured firstly by white light scanning interferometry to get an overall coarse morphology, and then, further measured with higher resolution by AFM. Several measuring experiments on standard samples demonstrate the system’s good measurement performance and feasibility of the hybrid measurement method

Artificial intelligence in global health equity: an evaluation and discussion on the application of ChatGPT, in the Chinese National Medical Licensing Examination

BackgroundThe demand for healthcare is increasing globally, with notable disparities in access to resources, especially in Asia, Africa, and Latin America. The rapid development of Artificial Intelligence (AI) technologies, such as OpenAI’s ChatGPT, has shown promise in revolutionizing healthcare. However, potential challenges, including the need for specialized medical training, privacy concerns, and language bias, require attention.MethodsTo assess the applicability and limitations of ChatGPT in Chinese and English settings, we designed an experiment evaluating its performance in the 2022 National Medical Licensing Examination (NMLE) in China. For a standardized evaluation, we used the comprehensive written part of the NMLE, translated into English by a bilingual expert. All questions were input into ChatGPT, which provided answers and reasons for choosing them. Responses were evaluated for “information quality” using the Likert scale.ResultsChatGPT demonstrated a correct response rate of 81.25% for Chinese and 86.25% for English questions. Logistic regression analysis showed that neither the difficulty nor the subject matter of the questions was a significant factor in AI errors. The Brier Scores, indicating predictive accuracy, were 0.19 for Chinese and 0.14 for English, indicating good predictive performance. The average quality score for English responses was excellent (4.43 point), slightly higher than for Chinese (4.34 point).ConclusionWhile AI language models like ChatGPT show promise for global healthcare, language bias is a key challenge. Ensuring that such technologies are robustly trained and sensitive to multiple languages and cultures is vital. Further research into AI’s role in healthcare, particularly in areas with limited resources, is warranted

Atrophy patterns in hippocampal subregions and their relationship with cognitive function in fibromyalgia patients with mild cognitive impairment

ObjectivesFibromyalgia (FM) has been associated with decreased hippocampal volume; however, the atrophy patterns of hippocampal subregions have not yet been identified. We therefore aimed to evaluate the volumes of hippocampal subregions in FM patients with mild cognitive impairment (MCI), and to explore the relationship between different subregional alterations and cognitive function.MethodsThe study included 35 FM patients (21 with MCI and 14 without MCI) and 35 healthy subjects. All subjects performed the Montreal Cognitive Assessment (MoCA) to assess cognitive function. FreeSurfer V.7.3.2 was used to calculate hippocampal subregion volumes. We then compared hippocampal subregion volumes between the groups, and analyzed the relationship between hippocampal subregion volume and cognitive function using a partial correlation analysis method.ResultsCompared with the healthy subjects, FM patients with MCI had smaller hippocampal volumes in the left and right CA1 head, Molecular layer head, GC-DG head, and CA4 head, and in the left Presubiculum head. Poorer executive function, naming ability, and attention were associated with left CA1 head and left Molecular layer head atrophy. By contrast, hippocampal subregion volumes in the FM patients without MCI were slightly larger than or similar to those in the healthy subjects, and were not significantly correlated with cognitive function.ConclusionSmaller volumes of left CA1 head and left Molecular layer head were associated with poorer executive function, naming ability, and attention in FM patients with MCI. However, these results were not observed in the FM patients without MCI. These findings suggest that the hippocampal subregions of FM patients might present compensatory mechanisms before cognitive decline occurs

Voltage-Dependent Anion Channel 2 of Arabidopsis thaliana (AtVDAC2) Is Involved in ABA-Mediated Early Seedling Development

The voltage-dependent anion channel (VDAC) is the major transport protein in the outer membrane of mitochondria and plays crucial roles in energy metabolism, apoptosis, and metabolites transport. In plants, the expression of VDACs can be affected by different stresses, including drought, salinity and pathogen defense. In this study, we investigated the expression pattern of AtVDAC2 in A. thaliana and found ABA suppressed the accumulation of AtVDAC2 transcripts. Further, phenotype analysis of this VDAC deregulated-expression transgenic Arabidopsis plants indicated that AtVDAC2 anti-sense line showed an ABA-insensitivity phenotype during the early seedling development under ABA treatment. The results suggested that AtVDAC2 might be involved in ABA signaling in A. thaliana

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases