This review presents the Oncodarwinian Hypothesis, which proposes a new medical paradigm: that of cancer as a potential macro-immunoadaptive response (susceptible to fine-tuning or reprogramming/management via artificial intelligence-based 3D printed p53 superproteins). A traditional hypothesis-generation method was adopted; it entails observing a biophenomenon longitudinally (tumor-precursor out-of-control cell division), formulating and refining targeted research questions, and then, rooted in a prior interdisciplinary theoretical framework, outlining (per deductive reasoning) a testable answer or statement apt to predict outcomes. Two main theoretical findings emerge from this review: the plausibility of a wireless p53 superprotein molecular biochip (3D printed) and cancer cells’ dual-focus immunological nature. It will be necessary to approach the key issue and prognosis of (supposedly meaningless) uncontrolled cell division in a different light. Basically, the same diseasing cancer also constitutes a self-replicating immunoadaptive algorithm that needs to be deciphered. An interdisciplinary quest to unravel its “source code” involves genomic palaeontology and learning the natural selection programming language — for developing (personalized) artificial intelligence-assisted p53 superproteins.

Cell cycle checkpoint-related genes (CCCRGs) are implicated in the development and progression of hepatocellular carcinoma (HCC). However, their precise roles and underlying mechanisms remain insufficiently characterized and require further investigation. This study aimed to explore the prognostic significance of CCCRGs in HCC, and to investigate the mechanism by which they promote the progression of HCC.

HCC datasets from The Cancer Genome Atlas and International Cancer Genome Consortium were analyzed to identify hub genes. A prognostic model was constructed and validated using Kaplan–Meier analysis, nomogram, calibration curves, decision curve analysis, and receiver operating characteristic analysis. Immune infiltration patterns were assessed using single sample gene set enrichment analysis, while pathway activities were evaluated via gene set variation analysis. Single-cell RNA sequencing data from GSE149614 were analyzed with Seurat and CellChat to investigate cell–cell communication. Patient-derived HCC specimens were examined through immunohistological evaluation, HCC cell lines were used for in vitro functional assays, and in vivo tumor growth was assessed through animal experiments.

CCCRGs showed significant associations with prognosis, malignant biological behavior, and immune responses in HCC. Centromere protein (CENP) I was identified as a critical hub gene that markedly promoted HCC proliferation, metastasis, and epithelial–mesenchymal transition, while inhibiting apoptosis. Mechanistically, CENPI suppressed YAP phosphorylation, enhancing its nuclear translocation and thereby driving malignant progression. Additionally, CENPI impaired immune effector cell infiltration, likely by disrupting tumor antigen presentation and chemokine-mediated CD8+ T cell chemotaxis, thereby promoting immune escape.

This study underscores the prognostic significance of CCCRGs in HCC and identifies CENPI as a key driver of tumor progression through the Hippo pathway. Furthermore, it reveals CENPI’s role in promoting immune escape, suggesting novel therapeutic targets for HCC treatment.

Fiberoptic bronchoscopy involves various topical airway anesthesia protocols, which can impact patient comfort, procedural ease, and overall outcomes. This study aimed to compare pre-procedure lignocaine spray (PPL) and spray-as-you-go (SAYG) airway anesthesia in terms of patient discomfort and operator comfort during fiberoptic bronchoscopy.

A single-blind randomized controlled trial was conducted at the Pulmonology Department of Shaikh Zayed Hospital, Lahore, Pakistan, from March 2021 to March 2022. Fifty participants were randomly assigned to two groups (n = 25 each). Standard procedural sedation with midazolam and 2 mL of 4% lignocaine spray in the oropharynx was used to suppress the gag reflex. Additionally, 2% lignocaine spray was administered during the procedure according to body weight (3 mg/kg) via oral scope insertion. Cough severity, pain perception, and operator comfort were assessed using the Visual Analogue Scale, Faces Pain Rating Scale, and a 4-point Likert scale, respectively.

Demographic characteristics were comparable between the groups, with a minor age difference (PPL: 53.25 years vs. SAYG: 50.88 years, p = 0.017). No significant differences were observed in pain perception, cough scores, or procedure duration between the PPL and SAYG groups. Operator comfort scores showed a trend favoring PPL (60% rated as “comfortable” or “very comfortable” vs. 28% in SAYG), though the difference was not statistically significant (p = 0.108).

Both PPL and SAYG topical airway anesthesia methods demonstrated similar effectiveness in pain control, cough suppression, operator comfort, and procedure duration. There was a slight, non-significant preference for PPL in operator comfort. These findings suggest that either technique may be effectively used, with potential implications for procedural efficiency and patient outcomes.

Sedation monitoring is crucial in neurosurgical intensive care units to ensure optimal patient comfort and safety. However, sedation practices vary significantly. This study aimed to evaluate and summarize the evidence related to sedation monitoring in neurocritical care patients, with a focus on identifying best practices for improving monitoring accuracy and patient outcomes.

This study was conducted as an evidence summary, following the evidence summary reporting standards of the Fudan University Evidence-based Nursing Center. The evidence on sedation monitoring management in neurocritical care patients was systematically retrieved using the 6S evidence model, including clinical decisions, best practices, guidelines, expert consensus, evidence summaries, systematic reviews, and more. Searches of domestic and international databases covered all records from the databases’ inception to June 2024. Two researchers independently selected literature that met the inclusion criteria and conducted quality assessment, evidence-level evaluation, and evidence synthesis.

Ten high-quality studies were ultimately included. From these, twenty pieces of best evidence were extracted, covering four categories: monitoring personnel, monitoring targets, monitoring tools, and monitoring timing and content. Among these, fifteen pieces of evidence were classified as strong recommendations, while five were classified as weak recommendations.

This study summarized the best evidence on sedation monitoring for neurocritical care patients, providing guidance for clinical staff to improve sedation monitoring accuracy and patient outcomes in neurosurgical intensive care units.

Full or partial trisomy of human chromosome 21 results in dysregulation of gene expression, leading to the manifestation of specific phenotypes described in individuals with Down syndrome (DS). Defects in brain development, coupled with impairment in neurogenesis, are ultimately expressed as cognitive deficiency, Alzheimer disease (AD), and dementia. Amid the triplication of all human chromosome 21 (HSA21) genes, dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A)-mediated neurogenesis and dendritic development have been attributed to the learning and memory deficits and cognitive impairment in the DS population. Upregulated DYRK1A perturbs the development and function of the brain, collectively affecting neurogenesis, synaptogenesis, synaptic transmission, and cell signaling pathways, which might disproportionately produce inhibitory neurotransmission and contribute to the cognitive phenotype. However, the lack of distinct gene-phenotype associations acts as a potential barrier to therapeutic improvement of cognitive performance and amelioration of AD-related neurodegeneration. The present review aims to summarize the neurogenetic consequences of triplicated DYRK1A in the DS population in relation to sexual dimorphism and expression of the Apolipoprotein Eε4 (APOE ε4) genotype. Notably, normalization of trisomic DYRK1A demonstrated improved synaptic plasticity, glutamatergic/GABAergic (excitatory/inhibitory) balance, and learning and memory in DS mouse models. Therapeutic approaches using inhibitors of DYRK1A, including catechins present in green tea extract and several other natural and synthetic agents, produced variable outcomes in cognitive improvement, depending on age and dose of administration. Mitigation of impairment in neurogenetic differentiation and cognitive performance might help control AD-related dementia and enhance quality of life. This review highlights the consequences of upregulated DYRK1A kinase on impairment of neurogenesis and cognitive deficits, and the therapeutic challenges associated with DYRK1A inhibitors for ameliorating dysregulated gene expression in DS models and human DS.

Aging is characterized by a progressive decline in physiological function, an increased risk of chronic diseases, and multiple molecular and cellular alterations, including inflammation, oxidative stress, and mitochondrial dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for the treatment of type 2 diabetes and obesity, may modulate pathways associated with the hallmarks of aging. This review aims to summarize the mechanistic and therapeutic evidence for GLP-1 RAs in targeting key aging processes and their potential to restore cellular homeostasis and enhance healthspan. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025. Both preclinical and clinical studies were included if they evaluated the effects of GLP-1 RAs on the major biological processes encompassed by the 12 hallmarks of aging, such as mitochondrial dysfunction, insulin resistance, dysbiosis, inflammaging, autophagy, proteostasis, and genomic stability. Data were analyzed narratively to elucidate potential mechanisms and translational relevance. Evidence from animal and human studies demonstrates that GLP-1 RAs improve mitochondrial function, reduce oxidative stress, attenuate chronic inflammation, and enhance autophagic activity. Additionally, they modulate nutrient-sensing pathways and metabolic processes, thereby improving cellular resilience. Preclinical studies indicate neuroprotective, cardioprotective, and hepatoprotective effects, while emerging clinical data support improvements in metabolic and inflammatory profiles in older adults. Taken together, GLP-1 RAs exert pleiotropic effects across all 12 hallmarks of aging. Although long-term safety and efficacy require further evaluation, current evidence positions GLP-1 RAs as promising therapeutic agents in translational geroscience, with the potential to mitigate age-related physiological decline and promote a longer, healthier lifespan.

Cardiac pacemaker implantation is a primary therapy for various arrhythmic disorders; however, safety concerns persist in India. This study aimed to evaluate two-year safety outcomes of cardiac pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices in a tertiary care setting.

In this prospective cohort study, data collection was conducted over a one-year enrolment period (February 2023 to January 2024), encompassing patient demographics, pacemaker implantation details, indications, and comorbidities. Patients were prospectively followed for a total of two years from enrolment—during the data collection period and for an additional year, to record device-associated adverse events. Ethical approval was obtained (IECJNMC/1662), and data were analyzed using SPSS.

Among 183 patients, 95% received cardiac pacemakers, 3% cardiac resynchronization therapy devices, and 2% implantable cardioverter-defibrillators. The data comprised 58% males (mean age, 63 years). The adverse event rate was 5.5% (10/183), distributed as 3.8% device infection, 1.09% lead dislodgement, and 0.54% generator dysfunction, with no statistical difference between males and females (P > 0.05). Different age groups, various indications, and several comorbidities showed no significant disparities (P > 0.05) between males and females. The Cox model showed no significant effect of several predictors on the occurrence of adverse events (P > 0.05). The Kaplan–Meier survival curve revealed a higher incidence of adverse events in the first six months, followed by stabilization. Adverse events were appropriately documented and reported to the Indian Pharmacopoeia Commission.

The observed adverse event rate of 5.5% supports previous Indian and international data; however, the smaller sample size and short follow-up duration warrant further investigation for more specific outcomes.

Clove essential oil (CEO) derived from Syzygium aromaticum and miswak (Salvadora persica) contains bioactive compounds with antimicrobial properties. Due to the growing interest in alternatives to conventional antibiotics, this study aimed to evaluate the in vitro antimicrobial efficacy of CEO, miswak, and their combination against key peri-implantitis pathogens.

The antimicrobial activities of CEO, miswak, and their combinations were tested against Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. Disc diffusion and serial dilution methods were used to measure the inhibition zones and minimum inhibitory concentrations, respectively. Doxycycline served as a standard antibiotic for comparison, while ethanol was used as a negative control. Data were analyzed using one-way analysis of variance and Tukey’s honestly significant difference test, with significance set at α = 0.05.

CEO exhibited inhibition zones of 10–16 mm, comparable to that of doxycycline (13–16 mm), whereas miswak (6–13 mm vs. 1–14 mm) and the CEO–miswak combination (8–14 mm vs. 0–14 mm) showed lower activity. Mean minimum inhibitory concentration values were lowest for doxycycline (1.73 ± 0.46 µg/mL), followed by CEO (2.37 ± 0.24 µg/mL) and CEO–miswak combination (2.92 ± 0.12 µg/mL). Statistical analysis showed that the CEO–miswak combination was less effective than CEO (p = 0.0326) and doxycycline (p = 0.0001), but not different from miswak (p = 0.9836). CEO showed slightly greater activity than miswak (p = 0.0605).

Among the natural extracts tested, CEO exhibited superior antimicrobial efficacy, whereas miswak was less effective. The combination of CEO with miswak did not enhance antimicrobial efficacy, suggesting antagonistic interactions between their bioactive compounds.

Peginterferon-α treatment exhibits low rates of the serological conversion rate of hepatitis B e antigen (HBeAg) and the negative conversion rate of hepatitis B virus (HBV) DNA, with significant myelosuppression leading to treatment discontinuation in some patients. Traditional Chinese medicine (TCM) may ameliorate liver inflammation and modulate immune responses. This study aims to investigate the efficacy of combining TCM with pegylated-interferon (PEG-IFN) α-2b and its impact on myelosuppression adverse effects.

This study included 117 HBeAg-positive chronic hepatitis B (CHB) patients who started initial antiviral therapy at Xiamen Hospital of TCM between June 2018 and January 2023. According to the treatment regimen, patients were divided into the observation group (n = 56, receiving PEG-IFN α-2b combined with Licorice 15 g, Angelica sinensis 20 g, Poria 20 g, Paeonia lactiflora 20 g, Rhizoma Atractylodis Macrocephalae 20 g, Radix Bupleurum Chinense 20 g, Mentha piperita 3 g, Ginger three slices for more than six months) and the control group (n = 61, receiving PEG-IFN α-2b alone). This study retrospectively analyzed etiological indicators, liver biochemical indicators, and blood routine tests before and after treatment.

After 24 and 48 weeks of treatment, the observation group demonstrated significantly superior outcomes to the control group in quantitative reduction of hepatitis B surface antigen, the serological conversion rate of HBeAg, and the reduction in HBV DNA quantification (P < 0.05). By week 48, the HBV DNA negative conversion rate in the observation group (46.67%) was significantly higher than that in the control group (26.67%) (P < 0.05). Regarding safety, the incidence of myelosuppression in the observation group was significantly lower than that in the control group at both 24 and 48 weeks of treatment (P < 0.05)

Real-world findings demonstrate that adjunctive TCM significantly enhances the antiviral efficacy of peginterferon α-2b in HBeAg-positive CHB patients while concurrently mitigating treatment-limiting myelosuppression. This combination strategy may represent a clinically valuable approach to optimizing interferon-based therapy for CHB.

COVID-19 has resulted in significant long-term sequelae in convalescent patients, impacting overall quality of life. Traditional Chinese medicine (TCM) has shown promise in managing post-COVID-19 symptoms through syndrome differentiation. This study aimed to evaluate the efficacy and safety of TCM in COVID-19 convalescent patients in a real-world setting.

This prospective, real-world study will be conducted at Guangdong Provincial Hospital of Traditional Chinese Medicine. A total of 528 COVID-19 convalescent patients will be recruited and divided into two groups: a control group receiving routine Western medical treatment and an intervention group receiving additional TCM treatment based on syndrome differentiation. Patients will be assessed for three major TCM syndromes: Lung-Spleen Qi Deficiency, Qi-Yin Deficiency, and Cold Phlegm Obstructing the Lung, with corresponding TCM prescriptions administered accordingly. The primary outcome measure will be the improvement in clinical symptom scores based on a TCM symptom scoring system. Secondary outcomes will include changes in laboratory tests, imaging studies, heart function classification, and quality of life scores. Safety will be assessed through liver and kidney function tests and adverse event monitoring.

The study is expected to demonstrate that TCM treatment, based on syndrome differentiation, can significantly improve clinical symptoms and overall health in COVID-19 convalescent patients compared to routine Western medical treatment. These findings will provide evidence for integrating TCM into post-acute COVID-19 care.

This study will contribute to the evidence supporting TCM as an effective treatment for post-COVID-19 syndrome, enhancing patient outcomes and informing comprehensive recovery strategies.