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Molecular targeted therapy in combination with chemotherapy for the treatment of platinum-resistant/refractory ovarian cancer (PROC): a systematic review and network meta-analysis.

BACKGROUND: Although single-agent chemotherapy is the most common approach for treating platinum-resistant or refractory ovarian cancer (PROC), there is growing evidence that combining molecular targeted agents with chemotherapy is beneficial, especially for certain patient groups. However, the most effective combination regimen remains elusive. OBJECTIVES: This Bayesian network meta-analysis (NMA) aims to identify the best combination therapy for PROC. METHODS: Relevant studies were searched in PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials from their inception until October 2024. The primary outcomes were overall survival (OS), progression-free survival (PFS) and adverse events (AEs). Statistical analyses were performed using the GEMTC package (1.0-2) and R 4.2.0. This review was registered in PROSPERO (CRD42023428414). RESULTS: Our analysis of 22 randomized controlled trials (RCTs) (n = 3408) demonstrated that chemotherapy combinations with bevacizumab (hazard ratio (HR) = 0.52-0.65), sorafenib (HR = 0.65, 95% confidence interval (CI): 0.45-0.93) or adavosertib (HR = 0.56, 95%CI: 0.35-0.90) significantly improved OS and PFS versus chemotherapy alone. Notably, adavosertib + gemcitabine was associated with an increased risk of grade 3-4 AEs (relative risk (RR) = 1.8, 95%CI: 1.3-2.7), but these were generally manageable. CONCLUSIONS: Bevacizumab-based combinations demonstrate consistent benefits across multiple regimens for PROC. Paclitaxel + bevacizumab emerges as the optimal balance of efficacy and safety. Topotecan + sorafenib could be an alternative for patients who are ineligible for anti-angiogenic therapy.

Humans

Efficacy and Safety of Celecoxib Combined With Jintiange Capsules for the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND Knee osteoarthritis (KOA) poses a substantial global health burden, and conventional nonsteroidal anti-inflammatory drug (NSAID) therapy with celecoxib is hindered by adverse effects. This study evaluated the efficacy and safety of combining celecoxib with Jintiange capsules, a synthetic tiger bone formulation used in traditional Chinese medicine (TCM), to manage symptomatic KOA. MATERIAL AND METHODS This 12-week, randomized, double-blind, placebo-controlled trial enrolled 120 patients with KOA (age &#xf0b3;40 years; visual analog scale [VAS] score 4-7). Participants received celecoxib (200 mg/day tapered to 100 mg/day) combined with either Jintiange capsules (3.6 g/day) or placebo. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included WOMAC subscale scores (pain, function, and stiffness), VAS scores, and adverse drug reaction reports. RESULTS The experimental group demonstrated a 23.5-point (37.8%) reduction in WOMAC total score from baseline (P<0.001); the control group showed a 13.2-point (21.6%) reduction (P<0.001). The experimental group achieved 51.6% improvement in the WOMAC pain subscale (P<0.001), whereas the control group showed 33.3% improvement (P<0.001). Relative to the control group, the experimental group demonstrated a greater reduction in VAS score (P<0.001). Combined TCM-NSAID therapy produced significantly greater pain relief and functional improvement than NSAID monotherapy. CONCLUSIONS Celecoxib combined with Jintiange capsules provided clinically meaningful improvements in pain relief and functional outcomes relative to celecoxib monotherapy in patients with KOA. These findings support integration of TCM with conventional pharmacotherapy for osteoarthritis management.

Humans

Comparing the efficacy of chlorhexidine and povidone-iodine for surgical site disinfection: a systematic review and meta-analysis from randomized controlled trials.

BACKGROUND: Randomized controlled trials report conflicting evidence on the efficacy of different skin disinfectants for preventing surgical site infection (SSI). METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and Embase for RCTs published up to February 2025 comparing preoperative skin disinfection with povidone-iodine (PVI) versus chlorhexidine (CH). Primary outcomes were overall, superficial, deep, and organ/space SSI rates. Secondary outcomes included hospital stay, readmission, and reoperation. RESULTS: CH was superior to PVI in preventing overall SSI (26 studies, n = 29,356; RR: 0.89; 95% confidence interval [CI]: 0.80 to 0.99). The overall SSI incidence rate in the CH group was 7.1% (1,045/14,677), compared with 7.8% (1,152/14,679) in the PVI group, equating to an 11% reduction in relative risk and a 0.7% reduction in absolute risk. The number needed to treat to prevent one SSI was 143. CH demonstrated superiority over PVI in preventing superficial SSI (13 studies, n = 16,867; RR: 0.77; 95% CI: 0.64 to 0.92), but not for deep SSI (11 studies, n = 15,842; RR: 1.00; 95% CI: 0.77 to 1.29) or organ SSI (9 studies, n = 9,471; RR: 1.17; 95% CI: 0.89 to 1.53). No significant differences were found in hospital stay, readmission, or reoperation rates between the two groups. CONCLUSION: CH demonstrates statistical superiority over PVI in preventing overall and superficial SSI, though the absolute clinical benefit is modest. No significant differences were observed for deep or organ/space SSI, nor for secondary outcomes including hospital length of stay, readmission, or reoperation rates.

Humans

Assay-dependent variability in peptide biomarker quantification: experimental evidence from renalase in chronic kidney disease.

BACKGROUND: Renalase is a promising biomarker for kidney disease, but published levels vary widely between studies. We hypothesised that variability in commercial enzyme-linked immunosorbent assays (ELISAs) kits and matrix effects (serum vs plasma) drive these inconsistencies. METHODS: Paired serum and plasma samples from 56 participants (28 chronic kidney disease (CKD) stages 2-5, 28 healthy controls) were tested using three commercial renalase ELISAs (BTLAB, Cloud-Clone, EIAab). We assessed intra-assay precision, inter-assay agreement (Spearman's rank correlation and Bland-Altman analysis on log10-transformed values), matrix effects, and associations with estimated glomerular filtration rate (eGFR). Diagnostic performance was evaluated by Receiver operating characteristic (ROC) analysis. RESULTS: Inter-assay renalase concentrations differed markedly (up to orders of magnitude), with weak inter-assay correlations (r&#x2009;&#x2264;&#x2009;0.25). Bland-Altman analyses revealed large, systematic biases between kits. Only the BTLAB assay showed consistent serum/plasma agreement, a significant correlation with eGFR (&#x3c1;&#x2009;&#x2248;&#x2009;0.32-0.42, p&#x2009;<&#x2009;0.05), and moderate discriminatory performance for CKD in serum (AUC = 0.70) and plasma (AUC = 0.68). Cloud-Clone and EIAab produced divergent results and strong matrix-dependent biases. CONCLUSIONS: Observed variability among commercial ELISA platforms may compromise comparability between studies. Harmonisation, standardised reference materials, and cross-validation are necessary before renalase assays can be used reliably in clinical practice.

Humans

Risk of adverse events in elotuzumab-treated patients with multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Elotuzumab, an anti-SLAMF7 monoclonal antibody for multiple myeloma (MM), lacks&#xa0;a comprehensive safety profile from meta-analysis. METHODS: We&#xa0;systematically searched PubMed, Web of Science, EMBASE and CENTRAL through February 13, 2025 for randomized controlled trials (RCTs) evaluating elotuzumab in MM. Pooled relative risks(RRs) of adverse events observed in elotuzumab-containing regimens versus control therapies. RESULTS: 6 RCTs (N=1,736) were included. Elotuzumabsignificantly reduced incidence of neutropenia (RR = 0.86, 95% CI: 0.76-0.98), but increased risks of cough (RR = 1.41, 95% CI: 0.96-2.09), pneumonia (RR = 1.30, 95% CI: 1.07-1.59), diarrhea (RR = 1.16, 95% CI: 1.05-1.30), pyrexia (RR = 1.47, 95% CI: 1.10-1.96) and infections (RR = 1.09, 95% CI: 1.03-1.15). No significant differences were observed for anemia, thrombocytopenia, respiratory infections, nausea, appetite loss, back pain, muscle spasms, peripheral edema, insomnia, rash, pruritus, fatigue, or hypokalemia. For grade 3-4 events, elotuzumab was&#xa0;associated with higher risks of lymphopenia (RR = 1.86, 95% CI: 1.31-2.64, p&#x2009;=&#x2009;0.0005, I2 = 9%), diarrhea (RR = 1.47, 95% CI: 1.00-2.17), pneumonia (RR = 1.57, 95% CI: 1.11-2.23), cataracts (RR = 2.87, 95% CI: 1.15-7.21) and infections (RR = 1.30, 95% CI: 1.04-1.62). CONCLUSION: Elotuzumab in MM&#xa0;appears&#xa0;safe but with a specific&#xa0;adverse events pattern :&#xa0;lower neutropenia,&#xa0;but higher respiratory, gastrointestinal, metabolic, and infectious events. Differences may be influenced by longer treatment and corticosteroid use; therefore, interpretation of outcomes such as hyperglycemia and cataracts requires particular caution.

Humans

Intramuscular patient-derived xenografts achieve high engraftment rates in gastric cancer: implications for pharmacodynamic testing and genomic biomarker discovery.

BACKGROUND: Gastric cancer (GC) exhibits marked inter-patient heterogeneity, limiting empirical chemotherapy efficacy. Patient-derived xenograft (PDX) models preserve the molecular features of parental tumors and can serve as pharmacodynamic surrogates, but conventional subcutaneous PDX suffers from low engraftment rates. This study evaluated an optimized intramuscular PDX platform for individualized drug testing in GC and applied whole exome sequencing (WES) for biomarker identification (Clinical trial registry: ChiCTR-OOC-17012731). MATERIALS AND METHODS: Ninety-eight treatment-naive GC patients were enrolled between April 2018 and December 2020. Fresh tumor tissues were engrafted into NCG mice by intramuscular transplantation. Drug efficacy was evaluated using tumor cell necrosis rate and Ki-67 expression. WES was performed on 32 engrafted tumorgrafts to characterize driver mutations in fast- and slow-growing subgroups. RESULTS: An engraftment rate of 71.7% (43/60) was achieved, substantially exceeding rates reported in prior studies. Clinical characteristics were independent of engraftment success and outgrowth time (all p&#x2009;>&#x2009;0.05). Fast- and slow-growing tumorgrafts diverged in frequently altered genes: KMT2C, APOB, CDK12 and MSH2 predominated in fast-growing grafts, whereas TP53, CHD3 and TET2 were enriched in slow-growing grafts. Slow-growing tumorgrafts correlated with longer progression-free survival (p&#x2009;=&#x2009;0.02). PDX-guided treatment was associated with improved prognosis. CONCLUSIONS: Intramuscular transplantation into NCG mice yields high engraftment rates for GC PDX. PDX-guided chemotherapy selection is associated with favorable outcomes. Driver mutation divergence between fast- and slow-growing tumorgrafts provides candidate prognostic biomarkers.

Animals

Genetic determinants of gestational diabetes mellitus in thai pregnant women: role of GCKR, CDKAL1, TCF7L2, NEDD1, and CMIP variants.

BACKGROUND: Gestational diabetes mellitus (GDM) has a high global prevalence and arises from complex interactions between genetic predisposition and environmental factors. GDM is associated with metabolic disturbances and chronic low-grade inflammation, both of which contribute to its pathogenesis. This study aimed to investigate the association between GDM and 135 single-nucleotide polymorphisms (SNPs) across 20 genes related to metabolic traits. METHODS: In this case-control study, 152 pregnant women with GDM and 684 pregnant women with normal glucose tolerance (NGT) who underwent antenatal examination at Siriraj Hospital, Bangkok, were enrolled. Clinical data and blood samples were collected from all participants. Genomic DNA was isolated and subjected to whole-genome sequencing using the DNBSEQ-T7RS high-throughput sequencing platform. Genotype analyses were performed using R software, and haplotype analyses were conducted using the online SNPStats software. RESULTS: After adjusting for maternal age and pre-pregnancy body mass index, polymorphisms in TCF7L2 (rs34872471, rs7901695, rs4506565, rs7903146, rs12243326, and rs12255372), NEDD1 (rs10431408, rs11830756, rs249579, rs249585, and rs4762339), CMIP (rs2306115 and rs201681534), CDKAL1 (rs4710942), GCKR (rs2293572 and rs2293571), and GCK (rs5883890) were significantly associated with the risk of GDM. Haplotype analysis demonstrated that the TCF7L2 rs12243326-rs12255372 CA haplotype was associated with a decreased risk of GDM (OR = 0.44, 95% CI: 0.23-0.81), while the NEDD1 rs249579-rs249585-rs4762339 GGT haplotype was associated with an increased risk of GDM (OR = 1.40, 95% CI: 1.08-1.82). CONCLUSIONS: These findings suggest that genetic variations in TCF7L2, NEDD1, CMIP, CDKAL1, GCK, and GCKR contribute to GDM susceptibility in the Thai population.

Humans

Suicidality risk of cancer caregivers: a systematic review and meta-analysis of observational studies.

BACKGROUND: The increase in the number of global cancer cases is expected to lead to a greater caregiving burden. However, few studies have investigated the risk of suicidality among cancer caregivers. OBJECTIVE: The aim of this systematic review was to explore the risk of suicidality among cancer caregivers. METHODS: For this systematic review, a comprehensive search of the PubMed, Embase, Cochrane, Web of Science databases, PsycINFO and Scopus databases was conducted from inception to 16 July 2025. A meta-analysis was performed to determine the odds ratios (ORs) for case-control and cross-sectional studies and the adjusted hazard ratios (aHRs) for cohort studies. RESULTS: Seven studies were included (four cohort studies, one case-control study and two cross-sectional studies), and 638,188 study subjects and 4,203,957 nonexposed subjects. The meta-analyses revealed that the ORs was 1.91 (95% confidence interval [CI]: 1.46-2.49) in the case-control study, cross-sectional studies, and one cohort study which reported ORs, and the aHRs was 1.32 (95% CI: 1.16-1.50) in the three cohort studies. Caregivers of patients with highly aggressive cancers had a greater risk of suicidality (aHR = 1.66; 95% CI: 1.48-1.86). Within the first 7&#x2009;years following a patient's cancer diagnosis, the risk of suicidality among caregivers remained elevated (aHR = 1.42; 95% CI: 1.04-1.94). CONCLUSION: The results indicate the need for both clinical and societal awareness to reduce the risk of suicidality among cancer caregivers, especially those with highly aggressive cancers. TRIAL REGISTRATION: Registered prospectively in PROSPERO (https://www.crd.york.ac.uk/prospero/) with the registration number (PROSPERO CRD420251011926) and date of registration(15/03/2025).

Humans

Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.

BACKGROUND: COVID-19 has been closely associated with coagulation abnormalities. However, existing biomarkers, including D-dimer and fibrin degradation products (FDP), exhibit limited accuracy in stratifying disease severity and predicting long-term clinical outcomes. OBJECTIVES: This study aimed to use proteomic analysis to identify plasma biomarkers associated with COVID-19 severity and prognosis, and validate their predictive utility for mortality and thromboembolic complications. METHODS: Plasma proteomic profiles were analyzed across three COVID-19 severity classes. Differential expression analysis and functional analysis were performed. Clustering analysis was used to identify proteins correlated with disease severity. Candidate biomarkers were validated in an independent cohort. Predictive performance of the biomarkers for mortality, sepsis and venous thromboembolism was evaluated using bootstrap-corrected ROC analyses and multivariable regression analyses. RESULTS: Proteomic analysis revealed progressive involvement of the coagulation and complement pathway with increasing disease severity. SERPINA1 and CD59 were identified as candidate biomarkers and exhibited significantly higher plasma levels in severe cases. Bootstrap-corrected ROC analyses demonstrated strong predictive performance: SERPINA1 achieved AUCs of 0.775 and 0.924 for 30-day and 12-month mortality, and CD59 achieved AUCs of 0.720 for sepsis; the combined model further improved prediction of 12-month mortality (AUC 0.946) and sepsis (AUC 0.904), outperforming D-dimer and FDP. Multivariable regression confirmed their independent prognostic value. CONCLUSION: This exploratory study identifies SERPINA1 and CD59 as candidate prognostic biomarkers in COVID-19, highlighting the role of coagulation and complement-related pathways in disease severity and warranting further prospective validation.

Humans

Feasibility, Acceptability, and Preliminary Effectiveness of Family Navigation for Low-income Ethnoracially Diverse Preschoolers with Developmental Concern.

OBJECTIVE: To assess for feasibility, acceptability, and preliminary effectiveness of an ethnoracially-matched family navigation intervention aimed at reducing barriers to developmental evaluations for preschoolers with developmental concern attending Head Start. METHODS: Fifty-eight parents of Head Start preschoolers who were identified as at risk for developmental delay were assigned using stratified block random sampling to the family navigation intervention (n&#x2009;=&#x2009;28) and 30 controls (usual care). Key outcomes included the percentage of children who completed the planned intervention visits, satisfaction with the intervention, and the proportion of children guided by family navigators who completed developmental evaluations. RESULTS: Of the 28 families, 21 parents completed the family navigation intervention visits. The intervention sample was diverse, including 57% Black, 24% White, and 19% Latino(a) parents. Ninety percent of Head Start educators (n&#x2009;=&#x2009;18) and 100% of healthcare providers (n&#x2009;=&#x2009;6) were satisfied with the intervention. Parents qualitatively reported that they valued the advocacy support from the family navigators and navigators (n&#x2009;=&#x2009;7) valued their role in "giving back." Sixty-six percent of the intervention group were seen by a healthcare provider to discuss developmental concerns showing preliminary effectiveness for completion of healthcare evaluations. However, there was no significant difference between those in the intervention and control group completing Head Start recommended evaluations, and over half of all participants were not referred for educational evaluations. CONCLUSION: Results support the feasibility, acceptability, and preliminary effectiveness of an ethnoracially matched family navigation intervention to reduce barriers to developmental healthcare evaluations for preschoolers at risk for developmental delays. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03499405; Date of Registration: April 9, 2018.

Humans

Uce-based phylogeny and classification of Megachilini.

The generic-level classification of the bee tribe Megachilini (Megachilidae) has remained controversial due to poor phylogenetic resolution at the base of the group, particularly among the brood parasitic genera and the numerous dauber ("Chalicodoma s. l.") lineages. We present a phylogenomic analysis of Megachilini based on ultraconserved elements (UCEs), sampling 52 ingroup taxa with emphasis on the dauber lineages. We also present a combined UCE&#xa0;+&#xa0;six-gene analysis to improve taxon coverage, resulting in a dataset with 127 ingroup taxa. Maximum likelihood, coalescent, and Bayesian analyses of multiple UCE matrices recover largely congruent topologies with substantially improved support relative to previous studies. Our results strongly support the monophyly of Megachilini, the early divergence of Noteriades and Gronoceras, and a single origin of brood parasitism. All remaining non-parasitic Megachilini form a moderately supported clade sister to the brood parasitic lineage. The leafcutter bees are monophyletic and nested within dauber lineages. Several major dauber clades are consistently recovered, including an exclusively Australian clade corresponding to the Hackeriapis group of subgenera, while several recognized subgenera are paraphyletic. The lineage known as Morphella, previously placed in synonymy with the subgenus Callomegachile, was not closely related to that subgenus and is here treated as a valid subgenus. Divergence-time analyses place the crown age of Megachilini in the late Eocene to early Oligocene, with major extant lineages diversifying during the Miocene. Limited morphological diagnosability of several clades indicates that splitting non-parasitic lineages into numerous genera would result in an impractical classification that would widen the gap between taxonomists and non-specialists and exacerbate the taxonomic impediment in bees. We therefore advocate retaining a single genus Megachile for non-parasitic Megachilini (excluding Noteriades and Gronoceras), as the classification best supported by phylogenomic evidence and most robust to future taxon sampling.

Animals

Efficacy and safety of rib-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation at two different targets for primary palmar hyperhidrosis: a randomized controlled trial.

OBJECTIVES: To compare the efficacy and safety of computed tomography-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation (RFT) targeting the upper versus lateral margin of the fourth rib head for severe primary palmar hyperhidrosis (PPH). METHODS: Patients with severe PPH were randomly divided into Group U (upper margin target) and Group L (lateral margin target). Outcome measures included 1-year recurrence rate, Hyperhidrosis Disease Severity Scale (HDSS), Dermatology Life Quality Index (DLQI), palm skin temperature, finger perfusion index (PI), compensatory hyperhidrosis and patient satisfaction. RESULTS: Both groups (n&#x2009;=&#x2009;55 each, 110 sides) successfully underwent RFT. No preprocedural PI differences were found (p&#x2009;>&#x2009;0.05). Immediately post-RFT, PI in Group L was significantly higher than in Group U (left p&#x2009;=&#x2009;0.025, right p&#x2009;=&#x2009;0.013). No significant differences in HDSS grades were observed between groups before and at 1&#x2009;day, 2&#x2009;weeks, 1&#x2009;month and 3&#x2009;months post-procedure. However, at 6 and 12&#x2009;months, Group L showed significantly lower HDSS grades (left p&#x2009;=&#x2009;0.033 and 0.016; right p&#x2009;=&#x2009;0.039 and 0.025) and lower DLQI scores (p&#x2009;=&#x2009;0.037 and 0.024) than Group U. Patient satisfaction did not differ within 6&#x2009;months, but Group L had significantly higher satisfaction at 12&#x2009;months (p&#x2009;=&#x2009;0.036). CONCLUSIONS: Targeting the lateral margin of the fourth rib head for RFT achieved greater efficacy, better quality of life and higher patient satisfaction compared to the upper margin target.

Humans

Intervention components, training dose, and adherence in exercise-based prevention of hamstring strain injury in football: a systematic review and meta-analysis.

OBJECTIVE: To quantify associations between exercise-based prevention programmes and hamstring strain injury (HSI) risk in football participants, and whether training dose and adherence modify effects. METHODS: Six databases were searched to 1 October 2025. Randomised and cluster-randomised trials comparing HSI prevention programmes with usual practice or warm-up in football participants were included. Random-effects meta-analysis pooled risk ratios (RRs); subgroup analyses and meta-regression assessed effect modification. RESULTS: Fifteen trials (n = 7,465) were analysed. Programmes reduced HSI risk (RR = 0.51, 95% CI 0.36-0.71), with I&#xb2;=57% and a prediction interval crossing the null (0.18-1.40). Based on a control event rate of 7.8%, absolute risk reduction was 3.8% (38 fewer HSIs per 1000 participants; 95% CI 23-50 fewer). Effects were stronger for shorter interventions (1-6 months; RR = 0.43) than longer interventions (7-10 months; RR = 0.77; P for interaction=0.04), and for elite/semi-professional players (RR = 0.38) than amateur players (RR = 0.77; P for interaction = 0.02). Training frequency and weekly volume did not modify effects, whereas adherence did. High adherence (&#x2265;75%) was associated with lower HSI risk (RR = 0.36, 95% CI 0.28-0.48), whereas low adherence (<75%) showed no clear benefit (RR = 0.92, 95% CI 0.68-1.23; P for interaction <0.00001). Each 10% increase in adherence corresponded to an RR multiplier of 0.83 (approximately 17% lower RR). Certainty of evidence was low. CONCLUSION: Exercise-based programmes reduce HSI risk in football when implementation supports sustained adherence. Effects may be stronger in shorter interventions and elite populations, but evidence remains insufficient to differentiate programme types or components.

Humans

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14&#xa0;household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans

Tranexamic acid in spontaneous&#x2002;intracerebral&#x2002;hemorrhage: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tranexamic acid (TXA) is a well-established antifibrinolytic medication in the general population. However, its efficacy and safety for patients with spontaneous intracerebral hemorrhage (ICH) remain inconclusive. Consequently, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of TXA for spontaneous ICH. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following established methodological standards. Our search encompassed eight electronic databases from inception to April 25, 2024. The primary outcome was a reduction in all-cause mortality. The secondary outcomes included improvements in functional independence, neurological impairment, activities of daily living, and reduction in hematoma expansion (HE). Fixed-effects or random-effects model&#xa0;were performed for pooled data where eligible. RESULTS: A total of 9 RCTs that initially enrolled 3,124 patients were included. There were no significant differences observed concerning all-cause mortality (RR, 1.03; 95% CI [0.89-1.18]), hematoma expansion (RR, 0.90; 95% CI [0.80-1.00]), improvement of functional independence (RR, 1.02; 95% CI [0.92-1.12], neurological impairment (MD, -0.88 [95% CI, -2.22-0.45]), or activities in daily living (MD, -0.83 [95% CI, -29.25-12.59]). The pooled data indicated that TXA for ICH was associated with a decrease in hematoma volume from baseline (MD, -1.74; 95% CI [-2.47 to -1.02]). No significant difference in adverse events was observed between the TXA group and the control group. CONCLUSIONS: In summary, TXA does not affect all-cause mortality, functional outcomes, or neurological impairment, nor does it reduce HE, despite reducing hematoma volulume. TXA use for ICH requires careful clinical consideration.

Humans

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-&#x3ba;B, 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

Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies.

BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged &#x2265; 50&#x2009;years (n&#x2009;=&#x2009;7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g&#x2009;=&#x2009;1.60, 95% CI: 0.95-2.25) and 8-OHdG (g&#x2009;=&#x2009;2.64, 95% CI: 2.13-3.14) were markedly elevated (p&#x2009;<&#x2009;0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g&#x2009;=&#x2009;5.24). In PD, 8-OHdG was moderately elevated (g&#x2009;=&#x2009;0.78, 95% CI: 0.18-1.39; p&#x2009;=&#x2009;0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g&#x2009;=&#x2009;0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.

Humans

Effects of phenylephrine and norepinephrine with restrictive infusion on oxygenation during one-lung ventilation for lung surgery: a randomized controlled trial.

OBJECTIVE: This study compared&#xa0;the effects of norepinephrine or phenylephrine combined with restrictive infusion on the oxygenation during thoracoscopic one-lung ventilation (OLV). METHODS: Ninety patients were randomly divided into three groups: the norepinephrine group (Group N), the phenylephrine group (Group P), and the control group (Group C). Arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt fraction (Qs/Qt) were measured with patients in lateral positions during two-lung ventilation (TLV) at 10&#x2009;min (T1), and during OLV at 15&#x2009;min (T2) and 45&#x2009;min (T3). Lung tissue samples were analyzed for endothelin and COX-2 levels after surgery. RESULTS: At T3, Group P had significantly higher PaO2 and lower Qs/Qt than Groups N and C (all p&#x2009;<&#x2009;0.05), with no significant differences between Groups N and C (all p&#x2009;>&#x2009;0.05). Compared to T1, Groups N and C showed significantly lower PaO2 and higher Qs/Qt at T2 and T3 (all p&#x2009;<&#x2009;0.05), with no significant differences in PaO2 and Qs/Qt at T3 compared with T2 (all p&#x2009;>&#x2009;0.05). Group P patients had lower PaO2 and higher Qs/Qt at T2 and T3 compared to T1 (all p&#x2009;<&#x2009;0.05), but at T3, PaO2 increased and Qs/Qt decreased compared to T2 (all p&#x2009;<&#x2009;0.05). Lung tissue levels of endothelin and COX-2 were significantly elevated in group P compared to groups N and C (all p&#x2009;<&#x2009;0.05). CONCLUSION: Combining phenylephrine with restrictive infusion during OLV improved oxygenation by increasing PaO2, decreasing Qs/Qt, and raising endothelin and COX-2 levels in lung tissue, thereby enhancing the HPV effect.

Humans