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PubMed2026

Anti-inflammatory agents after hip and shoulder arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. OBJECTIVES: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. RESULTS: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. CONCLUSION: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Humans↗

PubMed2026

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60 days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals↗

PubMed2026

Safety, pharmacokinetics and pharmacodynamics of TQC3721, an innovative, dual PDE3 and PDE4 inhibitor, in healthy subjects and patients with chronic obstructive pulmonary disease: Randomised, double-blind, placebo-controlled phase I and IIa clinical trials.

BACKGROUND AND PURPOSE: TQC3721 is a novel inhaled dual phosphodiesterase (PDE3/4) inhibitor designed to provide bronchodilation and anti-inflammatory effects for chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH: First-in-human randomised, double-blind, placebo-controlled phase I (SAD: 0.2 to 24 mg single dose; MAD: 12 mg once daily (QD) for 7 days in healthy subjects) and phase IIa studies (0.75 to 6 mg once or twice daily for 4 weeks in moderate-to-severe patients with COPD) were conducted. Primary outcomes included safety, pharmacokinetics (PKs) and pharmacodynamics (PDs), change from baseline of forced expiratory volume in the first second [FEV1], and FEV1 at 12 and 24 h post-dose on days 1 and 28. KEY RESULTS: TQC3721 was rapidly absorbed (median Tmax of 0.25 to 0.5 h), mainly by pulmonary absorption rather than gastrointestinal absorption, along with low systemic exposure and lack of significant accumulation. TQC3721 demonstrated favourable safety profiles in healthy subjects and patients with COPD. In patients with COPD, TQC3721 produced rapid and outstanding bronchodilation effect sustained over 12 h post-administration, with FEV1 peaking at approximately 2 h post-dose and returning to baseline levels by 12 h, which supports a twice-daily dosing regimen for the future, and peak FEV₁ improvements ranging from 186 to 272 ml across dose groups after 4 weeks of treatment. Moreover, twice-daily 3 and 6 mg regimens were recommended for further clinical study. CONCLUSIONS AND IMPLICATIONS: Pharmacokinetic features, significant bronchodilation effects and overall favourable safety characteristics support further clinical development of TQC3721 as a potential dual-mechanism therapy for COPD.

Adult↗

PubMed2026

Effectiveness of psychosocial and lifestyle interventions in promoting behaviour change and improving cognitive outcomes in older people with memory concerns: A systematic review.

BACKGROUND: Older adults with mild cognitive impairment or subjective cognitive decline have a greater dementia risk, particularly those from minority ethnic and socioeconomically disadvantaged backgrounds. Psychosocial and lifestyle interventions targeting modifiable risk factors offer hope for reducing risk, yet behavioural mechanisms remain unclear. This systematic review examines these mechanisms and associated outcomes. METHOD: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Web of Science, and Scopus for randomised control trials testing interventions that aimed to improve lifestyle and cognition in older adults with memory concerns. We explored behavioural mechanisms using the COM-B model and synthesised intervention effectiveness, overall and within underserved groups. We prioritised lower risk of bias studies. RESULTS: 26 studies described 23 randomised controlled trials (14 multidomain, 9 single domain interventions). Certainty of evidence that behaviour change was associated with cognition was low. Moderate-certainty evidence indicated that interventions providing a socially supportive environment and combining nutritional education and counselling for 6 + months improved diet. Physical activity improved primarily in interventions incorporating education, structured training, and enablement strategies (e.g., tailored programmes, providing tools). Interventions simultaneously targeting capability, opportunity and motivation showed greater overall effectiveness. Few studies recorded ethnicity (13%) or sociodemographic status (9%), and none explored their impact. CONCLUSIONS: Non-pharmacological interventions can help this population improve their lifestyles if they feel capable, equipped and motivated, highlighting the value of careful design and implementation. There is scarce evidence on how these interventions work for underserved populations. Future research should explore this to inform tailored interventions and develop equitable dementia prevention strategies.

Humans↗

PubMed2026

Surgical management of esophageal atresia with tracheoesophageal fistula in extremely low birth weight neonates: A systematic review.

BACKGROUND: Surgical management of esophageal atresia/tracheoesophageal fistula (EA/TEF) in extremely low birth weight (ELBW) neonates remains challenging and controversial. This study systematically reviews surgical strategies and outcomes in this population. METHODS: Following PRISMA guidelines, Cochrane, Embase, MEDLINE, Scopus, and Web of Science (2004-2024) were searched in February 2025 for studies on surgical management of ELBW neonates with EA/TEF (PROSPERO CRD42025636228). Fatal chromosomal abnormalities were excluded. Demographics, comorbidities, surgical techniques, and complications were analyzed descriptively. Risk of bias was assessed. RESULTS: Eleven publications (five case reports and six case series) comprising 30 patients (Gross type B/C = 1/29) met the eligibility criteria. Mean gestational age was 28.1 (23-34) weeks, and mean birth weight was 760.4 (422-995) g. Twelve primary repairs (PR) and 18 delayed primary repairs (DPR) were performed, including staged repair (n = 11), lower esophageal banding (n = 4), and other techniques (n = 3). Postoperatively, four anastomotic leaks were managed conservatively, six strictures and one recurrent TEF required endoscopic intervention, three fundoplications and two aortopexies were reported (follow-up: 1-198 months, n = 19). Overall mortality was 30% (PR: 8.3%; DPR: 44.4%). Mortality was 60% among neonates with major congenital heart defects (CHD) and 40% among those with VACTERL association. EA/TEF-related complications contributed to 33.3% of deaths. CONCLUSIONS: Mortality in this cohort remains high, particularly with major CHD, and is largely unrelated to EA/TEF-specific complications. In selected cases, PR appears feasible as an alternative to DPR, although conclusions are limited by the small sample size and heterogeneous studies.

Humans↗

PubMed2026

"Out of sync and overlooked" - Relationship between social jetlag and anxiety in adolescents: Systematic review and meta-analysis.

Anxiety is the most prevalent mental health difficulty in adolescence, a period characterised by a shift towards an eveningness chronotype that is not aligned with societal demands (i.e., school start times). Experiencing "social jetlag" (SJL), a discrepancy in weekday-weekend sleep timing, is proposed to be associated with increased anxiety. A PRISMA-compliant systematic review and meta-analysis was conducted to investigate the relationship between SJL and anxiety in adolescents (age range: 12-18 years). Systematic searches were conducted in PsycINFO, Web of Science, Embase, PubMed, MEDLINE, and ProQuest Dissertations & Theses Global on 14th November 2024 to retrieve empirical studies analysing the relationship between SJL and anxiety in 12-18-year-olds. A multi-level random-effect meta-analysis was conducted in R to estimate the magnitude of the association between SJL and anxiety. After screening 2,138 records, 18 studies were included in the systematic review, with 12 included in the meta-analysis (235,526 participants in total) and six in a narrative review. A small association was found between increased SJL and more severe anxiety (Fisher's z = 0.0614, 95% CI [0.0268, 0.0961], p = 0.0011). These findings highlight the importance of addressing behavioural strategies targeting healthy regular sleep as a tool to improve mental health in adolescence.

Adolescent↗

PubMed2026

Effects of multistrain probiotic supplementation on hepatic function and anthropometric parameters in patients with metabolic dysfunction-associated steatotic liver disease: a double-blind, randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent on a global scale. The gut microbiota is integral to its pathogenesis, prompting extensive research into microbiota modulation as a potential adjunctive therapeutic strategy. AIM: The study aimed to evaluate the effect of multistrain probiotics supplementation on hepatic function in patients with MASLD in a double-blind, randomized, controlled trial. The primary outcomes were changes in Fibrosis-4 index (FIB-4) and fatty liver index (FLI). Secondary outcomes included changes in anthropometric parameters, selected biochemical markers, and other liver-related indices. METHODS: A total of 64 patients with MASLD were randomly assigned to two groups receiving either placebo (C) or a probiotic mixture (PRO) containing the following bacterial strains: 50% Lactococcus lactis Rosell-1058, 25% Lacticaseibacillus casei Rosell-215, 12.5% Lactobacillus helveticus Rosell-52, 12.5% Bifidobacterium bifidum Rosell-71 for 12 wk. RESULTS: Significant group × time interactions were observed for FIB-4 (Q = 0.007), with reduction in the PRO group and increase in the C group (-0.05 vs. 0.10; P = 0.002). No significant interaction was found for FLI (Q = 0.942). Significant group × time interactions were also observed for aspartate aminotransferase (-2.87 vs. 1.87 U/L; Q = 0.003) and APRI (-0.03 vs. 0.02; Q = 0.001), favoring the PRO group (P < 0.001 for both). No significant changes were observed in anthropometric parameters, glucose levels, or lipid profile. CONCLUSIONS: In patients with MASLD, the 12-wk probiotic supplementation had a modest but statistically significant effect on FIB-4, aspartate aminotransferase, and APRI, with no significant effect on FLI or anthropometric and metabolic parameters. These findings suggest that this probiotic formulation may have potential benefits for liver function in MASLD. However, long-term studies incorporating imaging-based and histological endpoints are required to determine the clinical significance of these findings.

Humans↗

PubMed2026

Integrative machine learning and transcriptomic analysis reveals molecular mechanisms underlying low survival rate in larval Chinese Bahaba (Bahaba taipingensis).

Chinese Bahaba (Bahaba taipingensis) is a Class I protected marine fish endemic to China. Low larvae survival during artificial breeding severely hinder population recovery. To investigate the molecular mechanism of high mortality in larval fish, this study performed RNA-seq on liver from naturally deceased (ND) and mass-dead (MD) individuals, combined with least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms to screen for core signature genes. A total of 873 differentially expressed genes (DEGs) were identified, including 112 upregulated and 761 downregulated genes. GO and KEGG enrichment analyses revealed significant enrichment in amino acid metabolism disorders, one‑carbon folate pool impairment, PPAR signaling abnormalities, ECM-receptor interaction, focal adhesion pathway, indicating widespread metabolic suppression accompanied by extracellular matrix remodeling and signaling disturbances in the livers of MD fish. MAD pre-filtering combined with dual machine learning algorithms yielded 18 robust core signature genes, among which SLC38A4, MMP1, FADD, FKBP5, and APOB were consistently identified as high-frequency core genes by both algorithms. SLC38A4 exhibited the highest importance score in the RF model and was significantly downregulated, making it the primary molecule distinguishing ND from MD phenotypes. ROC curve analysis showed that both models achieved an AUC of 1.000 (95% CI lower bound: 0.610), confirming the precise discriminatory ability of the core genes. GSEA further demonstrated significant enrichment of this core gene set in ND samples. This study provides the first systematic elucidation of the molecular mechanisms underlying liver dysfunction in low survival rate B. taipingensis, characterized by amino acid transport impairment, metabolic reprogramming, and structural remodeling, offering theoretical foundations for health assessment, early mortality risk warning, and artificial breeding conservation of this species.

Animals↗

PubMed2026

Efficacy of dapagliflozin on hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: a pre-specified single-arm analysis from a randomized controlled trial.

AIM: To evaluate the association of dapagliflozin therapy with changes in hepatic steatosis and non-invasive fibrosis surrogate markers in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) over 12 months. METHODS: This is a pre-specified single-arm analysis from a randomised, open-label, parallel-group trial. Of 54 participants randomised to dapagliflozin 10 mg daily, 50 (92.6%) completed the 12-month follow-up and were included in the per-protocol analysis. Assessments at baseline, 3, 6, and 12 months included transient elastography (CAP and LSM), ultrasonography, and biochemical tests. Primary endpoints were changes in hepatic steatosis (CAP) and non-invasive fibrosis surrogates (LSM). RESULTS: Significant reductions were observed in hepatic steatosis (CAP: 316.7 to 245.7 dB/m; mean change - 71.02 dB/m, 95% CI: -63.4 to - 78.6; p < 0.001) and in liver stiffness as a non-invasive fibrosis surrogate (LSM: 8.59 to 7.28 kPa; mean change - 1.31 kPa, 95% CI: -0.92 to - 1.70; p < 0.001). Improvements were also observed in glycaemic control, body weight, lipid profile, liver enzymes, ultrasonographic steatosis grading, and serum fibrosis markers. Genitourinary infections were the most frequently reported adverse events (32%); no serious adverse events were recorded. CONCLUSIONS: Dapagliflozin was associated with significant improvements in hepatic steatosis, non-invasive fibrosis surrogate markers, metabolic parameters, and liver function in T2DM patients with MASLD over 12 months. These findings provide region-specific evidence for an Indian population and support further controlled investigation. However, these findings should be interpreted in light of the pre-specified single-arm design of this analysis, the open-label methodology, relatively small sample size, and the absence of liver biopsy confirmation.

Humans↗

PubMed2026

Long-term efficacy of cognitive behavioural therapy for insomnia (CBT-I) on depressive symptoms: A systematic review and meta-analysis of randomised controlled trials.

Depressive symptoms are common in individuals with persistent insomnia. Previous meta-analyses of randomised controlled trials (RCTs) showed that cognitive behavioural therapy for insomnia (CBT-I) can reduce depressive symptoms at post-treatment. However, the long-term maintenance of these improvements has never been systematically examined. To fill-in this gap, we conducted a systematic review and meta-analysis of the long-term (≥3 months) effects of CBT-I on depressive symptoms. The review was registered in PROSPERO (CRD420251146061). Only RCTs in adults with insomnia were considered. Pubmed, Scopus, Psycinfo, CINAHL, and Medline were searched up to 12 September 2025 with no predefined time constraints. From 5359 records initially retrieved, we included 53 articles reporting on 13,608 individuals. After outliers removal, random effects meta-analysis showed that CBT-I was superior to control conditions in reducing depressive symptoms at 3 [k = 29, d = -.35, [95% CI: -.49 to -.21], p < .001], 6 [k = 29, d = -.32, [95% CI: -.59 to -.05], p = .018], and 12 [k = 10, d = -.25, [95% CI: -.39 to -.12], p < .001] months follow-ups. Results demonstrate that the effects of CBT-I on depressive symptoms are sustained throughout the year following treatment, although effects may decline over time.

Humans↗

PubMed2026

Assessment of the safety and efficacy of sodium pentaborate pentahydrate in individuals with overweight and obesity: a randomized, double-blind, placebo-controlled, phase 1/2 dose-finding trial.

The present study aimed to examine the short-term safety and tolerability of sodium pentaborate pentahydrate (NaB) and to explore preliminary efficacy and dose selection as secondary objectives in individuals with overweight or obesity. In this randomized, double-blind, placebo-controlled, phase 1/2 trial, conducted from July 2024 to January 2025, 177 adults with overweight or obesity were randomized, of whom 116 completed the 12-week trial. Participants received placebo or NaB at doses of 200, 400, 600, 800, or 1,000 mg for 12 weeks, alongside a standardized diet and exercise programme. The primary safety objective was to investigate short-term safety and tolerability through adverse events, hypoglycaemic episodes, gastrointestinal adverse events, and changes in haematological and biochemical parameters. The primary exploratory efficacy outcome was percentage change in body weight from baseline to week 12. Secondary and exploratory efficacy outcomes included body weight, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, glycaemic markers, lipid parameters, and blood pressure. Baseline characteristics were broadly similar across groups (all p ≥ 0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400 mg (-2.6 kg), 600 mg (-1.2 kg), and 1,000 mg groups (-3.1 kg). Compared with placebo, the 1,000 mg dose resulted in the largest reductions in body weight (mean difference, -2.30 kg; p = 0.01) and BMI (mean difference, -0.85 kg/m2; p = 0.02). The 1,000 mg dose showed preliminary efficacy for reducing body weight and BMI over 12 weeks compared with placebo, with no major short-term safety signal and no clinically meaningful changes in renal, hepatic, or haematological markers. All reported adverse events were mild. These short-term findings are exploratory and require confirmation in future phase 3 trials with extended follow-up to investigate long-term safety and efficacy.

Humans↗

PubMed2026

Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial.

BACKGROUND: Evidence is limited regarding whether assigned protein targets modify responses to resistance training (RT) alone or to the same RT program plus cycling (concurrent training [CT]) in middle-aged and older women. This randomized 2 × 3 factorial trial examined bioelectrical impedance analysis (BIA)-derived skeletal muscle mass (SMM; primary outcome), other body composition outcomes, muscular and functional performance, and cycle-derived estimated VO₂max. METHODS: In this randomized 2 × 3 factorial trial, 108 women aged 40-77 years were assigned to 12 weeks of supervised RT or CT (identical RT followed by cycling) and protein targets of 0.8, 1.6, or 2.2 g·kg-1·d-1. Baseline-adjusted ANCOVA tested training × protein interactions and marginal training and protein effects. Complete-case analyses included 83 participants. RESULTS: For SMM, no training-condition × protein-target interaction (p = 0.856), marginal protein-target effect (p = 0.726), or marginal training-condition effect (p = 0.273) was detected. CT had a lower baseline-adjusted week-12 BFP than RT (adjusted difference, -2.04 percentage points; 95% CI, -2.94 to -1.14; p < 0.001). RT had a higher baseline-adjusted week-12 leg-press estimated 1-RM than CT (CT - RT: -6.68 kg; 95% CI, -8.32 to -5.04; p < 0.001), whereas CT had a higher baseline-adjusted week-12 cycle-derived estimated VO₂max (adjusted difference, 4.53 mL·kg-1·min-1; 95% CI, 3.80 to 5.25; p < 0.001). No detectable marginal protein-target effects or training-condition × protein-target interactions were observed for the key secondary outcomes. CONCLUSIONS: No detectable differences in SMM or key secondary outcomes were attributable to assigned protein target. Compared with RT, CT favored estimated aerobic fitness and BFP, whereas RT favored leg-press strength. Because CT included additional cycling and greater exercise exposure, these differences cannot be attributed solely to training modality. Null protein findings do not establish equivalence among doses.

Humans↗

PubMed2026

Ultrasound-guided high-voltage vs conventional pulsed radiofrequency in elderly cervical radiculopathy: A randomized controlled trial.

BACKGROUND: Elderly patients with cervical radiculopathy present therapeutic challenges owing to comorbidities and medication-related risks. Long-term pharmacotherapy and surgical interventions are often suboptimal, necessitating evaluation of optimized pulsed radiofrequency strategies under image guidance. OBJECTIVES: This superiority trial compared the efficacy and safety of ultrasound-guided cervical nerve root high-voltage pulsed radiofrequency (HVP-PRF) versus conventional pulsed radiofrequency (C-PRF) for pain management in elderly patients with cervical radiculopathy. METHODS: This single-center, parallel-group, assessor-blinded randomized controlled trial enrolled patients aged 60-85 years with cervical radiculopathy, randomly assigned (1:1) to HVP-PRF (70 V) or C-PRF (45 V). Procedures were performed under ultrasound guidance with sensory/motor stimulation confirmation and temperature ≤42°C. The primary outcome was change in upper-limb radiating pain on the Numeric Rating Scale (ΔNRS) from baseline to 3 months. Secondary outcomes included Neck Disability Index (NDI), neck pain NRS, Patient Global Impression of Change, responder rates, rescue analgesia use, and adverse events. Follow-up occurred at 1 week, 1, and 3 months. RESULTS: A total of 104 patients were randomized and 101 received treatment. At 3 months, HVP-PRF demonstrated significantly greater radiating pain improvement versus C-PRF (adjusted mean difference 1.24, 95% CI 0.46-2.02, P=0.002). Functional improvement (NDI) was superior in the HVP-PRF group at 3 months (AMD 6.47, 95% CI 2.11-10.83, P=0.004). Responder rates (≥50% pain reduction) were higher with HVP-PRF at 3 months (68.75% vs. 42.22%, OR 3.01, P=0.011) and 6 months (65.22% vs. 43.18%, OR 2.52, P=0.035). Rescue analgesic use was lower in the HVP-PRF group during 1-3 months intervals (both P<0.05). Adverse event rates were comparable (27.45% vs. 32.00%). CONCLUSION: Under ultrasound visualization and electrical stimulation-based target confirmation with temperature control ≤42°C, HVP-PRF provided greater and more durable relief of upper limb radiating pain compared with C-PRF in elderly patients with cervical radiculopathy, with a comparable safety profile.

Humans↗

PubMed2026

Aflatoxins and their biosynthetic precursors in lotus seeds: simultaneous UPLC-MS/MS determination, contamination profiling, and matrix-specific accumulation during Aspergillus flavus infection.

Aflatoxin (AF) contamination poses a severe global threat to food and medicinal material safety, yet existing research focuses on terminal AF metabolites while neglecting residual biosynthetic precursors, leading to potential underestimation of contamination risks. In this study, a UPLC-MS/MS method was established for the simultaneous quantification of six AFs and their five precursors in lotus seeds, with optimization of mass spectrum parameters, chromatographic separation conditions, and sample pretreatment. Method validation confirmed linearity (R2 > 0.99), LODs (0.03-0.36 μg/kg), and recoveries (76.53%-120.0%, RSD < 15%). Analysis of 41 natural lotus seed samples revealed a 63.4% AF contamination rate, dominated by B-group AFs, while O-methylsterigmatocystin (OMST) and versicolorin hemiacetal (VOH) were identified as the primary co-residual precursors with co-occurrence rates ≥ 50%. Notably, AFM1 was predominantly detected in natural samples with AFB1 concentrations exceeding 100 μg/kg. Artificial inoculation experiments further demonstrated that sterilization and sealing conditions modulated AF biosynthesis in lotus seeds, with non-sterilized and non-sealed groups showing delayed fungal metabolism and lower toxin accumulation. A significant linear correlation was observed between AFM1 and AFB1 levels (r = 0.94) in infected samples, demonstrating their accumulation levels are coupled with fungal overall metabolic flux. Given the high co-occurrence rate of OMST/VOH with AFB1 in natural samples, their individual and combined toxicities require in-depth investigation. This work deciphers matrix-specific AF dynamics in lotus seeds, supporting regulatory standard refinement (e.g., precursor inclusion) and targeted control (e.g., time-sensitive drying after harvest). Further studies will focus on exploring the molecular mechanisms of substrate-dependent AF synthesis.

Aflatoxins↗

PubMed2026

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans↗

PubMed2026

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-κB, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans↗

PubMed2026

Intravenous lidocaine reduces the propofol EC50 for loss of consciousness and intraoperative anesthetic consumption in gynecological laparoscopy: A randomized controlled trial.

BACKGROUND: Intravenous lidocaine reduces propofol requirements and procedure-related adverse events. OBJECTIVES: The study aimed to test whether intravenous lidocaine would reduce the effect-site concentration of propofol required to achieve loss of consciousness and decrease propofol consumption during total intravenous anesthesia in gynecological laparoscopy. METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial. Sixty patients were randomly allocated to receive either intravenous lidocaine (1.5 mg·kg-¹ bolus) followed by continuous infusion or an equal volume of saline. Propofol was administered via target-controlled infusion starting at an effect-site concentration of 3.5 μg/mL. The concentration was then adjusted in steps of 0.5 μg/mLaccording to Dixon's up-and-down sequential method: decreased if loss of consciousness was achieved, or increased if not. Loss of consciousness was defined as loss of response to verbal commands. The median effective concentration (EC50) of propofol for inducing loss of consciousness was calculated using the Dixon's up-and-down method. General anesthesia was maintained with propofol and remifentanil, guided by state entropy (target 40-60) and surgical pleth index (target 20-50). Drug consumption was normalized to anesthesia duration and body weight. RESULTS: The estimated EC50 of propofol for inducing loss of consciousness was significantly lower in the lidocaine group than in the saline group (3.32 μg/mL, 95% Confidence Interval (CI): 3.04-3.59 vs. 3.89 μg/mL, 95% CI: 3.50-4.28). Under the study protocol, the lidocaine group also required less propofol (8.62 mg·kg-1·h-1, 95% CI: 8.10-9.15 vs. 9.89 mg·kg-1·h-1, 95% CI: 9.05-10.73) and less remifentanil (0.23 μg·kg-1·min-1, 95% CI: 0.21-0.24 vs. 0.27 μg·kg-1·min-1, 95% CI: 0.24-0.30) compared with the saline group. CONCLUSION: Intravenous lidocaine reduced the propofol EC50 for Loss of Consciousness (LOC) and decreased intraoperative propofol and remifentanil consumptions in patients undergoing gynecological laparoscopy. These findings suggest a propofol- and opioid-sparing effect of intravenous lidocaine in this setting, although confirmation in larger multicenter trials is needed.

Humans↗

PubMed2026

Mobile health apps improve Health-Related Quality of Life in Type 2 Diabetes Mellitus by enhancing medication adherence: A multicentre randomised controlled trial with mediation analysis.

AIMS: This study evaluated whether a gamified mHealth application (CareAide®) improves Health-Related Quality of Life (HRQoL) in Type 2 Diabetes Mellitus (T2DM) and whether this effect is mediated by medication adherence. METHODS: Prespecified secondary analysis of the T2DM cohort from a 6-month multicentre RCT (NCT06068309; N = 663; three Malaysian hospitals). Participants were randomised 1:1 to standard care or CareAide®. Adherence (MMAS-8), EQ-5D-5L utility (Malaysian value set), and AQoL-6D were assessed at baseline and 6 months. Simple mediation analysis (PROCESS Model 4; 5000 bootstraps) adjusted for baseline HRQoL. RESULTS: CareAide® significantly predicted higher MMAS-8 scores (mean difference +1.756; d = 1.638; p < 0.001). Higher MMAS-8 scores significantly predicted improved AQoL-6D utility (b = 0.024; p < 0.001). The direct effect on AQoL-6D was non-significant (p = 0.248). Bootstrapped indirect effect confirmed full mediation via AQoL-6D (0.042; 95% CI [0.024, 0.060]). A sensitivity analysis adjusting for baseline HbA1c confirmed full mediation (indirect = 0.034; 95% CI [0.015, 0.052]; n = 563). EQ-5D-5L utility showed a significant direct between-group difference at 6 months (p = 0.012) but did not operate as a mediation outcome. CONCLUSIONS: Medication adherence fully mediates the AQoL-6D HRQoL benefit of a gamified mHealth intervention in T2DM, as confirmed by both the primary and HbA1c-adjusted sensitivity analyses. These findings support integration of behaviourally informed digital adjuncts into routine primary diabetes care.

Humans↗