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Cystic fibrosis (CF) is an inherited multi-organ disorder. People with CF (pwCF) experience recurrent and chronic lung infections and a progressive loss of lung function. PwCF with poor and rapidly declining lung function may be considered for lung transplantation (LTx), which may improve their quality of life and survival. Nontuberculous mycobacteria (NTM) can cause pulmonary disease in pwCF, and NTM infection is a poor prognostic factor in LTx. Guidelines recommend NTM infection should not automatically preclude LTx. It is important to evaluate the evidence base for LTx in pwCF and NTM pulmonary disease. To evaluate clinical outcomes in pwCF and with NTM infection (NTM infection alone or with NTM pulmonary disease) who undergo LTx by comparing: 1. pwCF with current NTM lung infection who undergo LTx versus those with NTM infection who do not undergo LTX; 2. pwCF with current NTM lung infection who undergo LTx versus those without NTM undergoing LTx. We searched the Cochrane Cystic Fibrosis Trials Register, CENTRAL, MEDLINE, Embase, and PubMed as well as two ongoing trials registries. We checked references. The latest search date was 17 February 2026. We considered non-randomised studies of pwCF (any age) with or without NTM lung infection or disease being considered for LTx as well as studies of pwCF and NTM who either did or did not undergo LTx. Our critical outcomes were mortality, disseminated NTM infection post-LTx, time to chronic lung allograft dysfunction (CLAD), and quality of life at any time points reported. We additionally planned to report lung function, hospitalisations for pulmonary exacerbations, and nutritional parameters in the review. We assessed the risk of bias in three studies using ROBINS-I and in one study using the Joanna Briggs Institute checklist for case series. We could only report results narratively. We used GRADE to assess the certainty of the evidence. We included four single-centre retrospective studies (388 adults). Sample sizes ranged from nine to 177 participants. Mycobacteria abscessus was the most common NTM species identified, and all studies reported infection with other pathogens. All studies compared pwCF and NTM infection to pwCF without NTM infection, all undergoing LTx. Each study reported mortality and disseminated NTM infection post-LTx; two studies recorded CLAD. No study reported quality of life, specific lung function measures (although one study commented briefly on lung function in general), hospitalisations for pulmonary exacerbations, or nutritional parameters. We analysed all NTM infections together for practical reasons and were not able to undertake a planned subgroup analysis by subspecies, but acknowledge that the prognosis and clinical trajectory of pwCF infected with different NTM may not be similar. We downgraded the certainty of the evidence due to non-randomised study design and serious risk of bias across all studies. We assessed all identified evidence as of very low certainty, such that lung transplant may have little to no effect on any of the outcomes listed below, but the evidence is very uncertain. Mortality Two studies (18 participants with NTM) reported similar survival data between NTM-positive LTx recipients and matched controls without NTM. Another study (9 participants) reported that two of five participants NTM-positive at LTx died within a few months post-LTx, whilst one of four NTM-negative participants died three years post-LTx due to chronic rejection. One study (177 participants) found that pwCF who had positive NTM cultures pre-LTx had a longer median survival duration than those who had negative cultures. This study additionally reported on survival of participants with post-LTx NTM infection, finding that the five participants who had post-LTx NTM disease had a longer mean survival duration than the 141 participants without post-LTx NTM disease. Disseminated NTM infection post-LTx In the largest study, of the 18 pwCF with NTM at the time of LTx, seven had at least one positive NTM culture, and four developed NTM disease post-LTx. Conversely, 79 of the 89 pwCF without NTM remained so post-LTx; 10 participants recorded a positive NTM culture, but none developed NTM disease. For the 39 participants without a baseline NTM culture, three participants recorded positive NTM cultures post-LTx, and one developed NTM disease. Of the remaining small studies, one reported that NTM was isolated in four of 13 participants at LTx and in three of these post-LTx. A second study reported that one out of five pwCF had NTM infection post-LTx (all were positive at LTx). The third study reported that five out of nine participants had NTM disease at LTx, and two of these five remained NTM-positive post-LTx. CLAD Two studies assessed CLAD. One study reported that none of the five NTM-positive LTx recipients developed CLAD, stating that the risk of CLAD appeared to be similar between the NTM and the comparator group. The second study stated that three out of nine LTx recipients with NTM disease developed chronic rejection or graft dysfunction. There are no randomised trials to guide clinicians and patients or their families when making decisions regarding LTx in pwCF with NTM. The available data come from observational studies and registry data, often with few people with NTM reported. It has not been possible to pool the available data in meta-analysis, and we are very uncertain of the effect of NTM on pwCF undergoing LTx on the risk of developing NTM disease post-LTx, survival after LTx, and the development of CLAD. The studies were small and at times contradictory. In the era of highly effective modulator treatments, as some centres do not offer LTx to people with a history of NTM, there is an urgent need for more data to guide decision-making. This review is part of a suite of reviews on NTM funded jointly by the CF Foundation and the CF Trust. Protocol registration (2024): www.crd.york.ac.uk/PROSPERO/view/562682.

Ensuring the long-term retention of healthcare professionals has become a central priority for strengthening the resilience and quality of Iran's health system. A comprehensive understanding of the diverse factors influencing retention, alongside those that may contribute to outward mobility, is essential for informed policymaking. This study adopts a multi-method approach, integrating qualitative inquiry with a scoping review, to explore the determinants shaping healthcare professionals' decisions to remain in or leave the national health system, the implications for workforce stability, and the effectiveness of current policy responses. By examining both individual and systemic dimensions, and by incorporating insights from migrant professionals, domestic policymakers, and existing evidence, this research contributes a nuanced perspective to the broader discourse on human resources for health in developing contexts. The originality of this study lies in combining first-hand qualitative data with a systematic synthesis of literature, allowing for an in-depth understanding of locally grounded drivers of retention and opportunities for strengthening Iran's health workforce. The research employed a qualitative, multi-phase design. In the first phase, semi-structured interviews were conducted with 15 Iranian healthcare professionals residing in countries such as the United States, Germany, Switzerland, Turkey, and Oman to understand their professional trajectories. In the second phase, interviews with 16 Iranian health administrators, policymakers, and senior professionals were undertaken to capture institutional and policy-level perspectives on retention challenges and opportunities. All interviews were transcribed verbatim and analyzed thematically. Complementing this, a scoping review was conducted to synthesize existing evidence, policy documents, and expert assessments related to the retention and mobility of Iran's health workforce. Data sources included PubMed, Scopus, and gray literature obtained through institutional repositories and local websites. Findings highlight several interrelated factors influencing workforce retention. Economic considerations including income stability, purchasing power, and access to research funding remain important determinants of professional commitment. Institutional dynamics such as transparent promotion pathways, supportive management, and opportunities for professional development also play a critical role. Importantly, Iran's integrated system of medical education and service delivery emerged as a key structural strength, providing early clinical exposure, strong professional identity formation, and continuity between training and practice advantages less commonly available in many other health systems. Participants noted that when financial incentives are combined with accessible professional development programs, equitable workload distribution, and recognition of professional contributions, retention outcomes improve substantially. While destination countries may offer expanded career pathways, the sense of belonging, family ties, and cultural identity were identified as influential factors supporting continued service in Iran. Governmental initiatives including compensation adjustments, training reforms, and targeted retention programs have yielded positive outcomes, though further coordination and sustained implementation are needed. Strengthening the retention of healthcare professionals in Iran requires a holistic strategy that integrates economic, organizational, educational, and governance reforms. Enhancing remuneration structures, investing in professional development and research capacity, reinforcing the advantages of Iran's integrated educational service system, and engaging with the healthcare diaspora can collectively support workforce stability. A multi-sectoral, evidence-informed approach has the potential to improve long-term retention, mitigate the need for outward mobility, and promote a more resilient and sustainable health system.

Better evaluation of the contribution of the main diseases, injuries, and risk factors for mortality and life expectancy is crucial for more efficient policy making at the national and subnational levels in Iran. The aim of this study is to assess the effect of emerging causes of mortality on health, specifically COVID-19, which can help policy makers implement preventive measures in similar situations. In this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we present estimates of cause-specific mortality at the national and subnational levels in Iran from 1990 to 2023. New to this iteration of GBD, we present a decomposition analysis of the contribution of specific causes of death to net gain or loss in life expectancy across 31 provinces of Iran. We used an array of data sources including censuses, vital registration, and surveys for national and subnational estimates. The two leading causes of death in Iran were ischaemic heart disease and stroke in both 1990 and 2019. However, in 2020 and 2021, the COVID-19 pandemic displaced the leading causes of death, ranking first with age-standardised mortality rates of 286·2 deaths (95% uncertainty interval 267·9-310·5) per 100 000 in 2020 and 250·0 deaths (233·2-272·5) per 100 000 in 2021. COVID-19 ranked second and tenth in 2022 and 2023, respectively. Life expectancy at birth for both sexes combined declined from 78·0 years (77·7-78·1) in 2019 to 74·3 years (74·0-74·4) in 2020. It steadily recovered to 78·8 years (78·5-79·2) in 2023. COVID-19 was the main cause of loss in life expectancy, by 4·19 years, between 2019 and 2020. There was a net gain of 12·4 years in life expectancy in Iran from 1990 to 2023. The net gain at the national level can be mostly attributed to reduced mortality from ischaemic heart disease (2·61 years), stroke (1·63 years), neonatal disorders (1·26 years), transport injuries (0·88 years), and neoplasms (0·64 years). The decline in mortality rates of major causes continued to 2023 despite the pandemic. An exception was Alzheimer's disease, which showed a 4·0% increase in rate between 2019 and 2023 and led to a net loss of 0·04 years in life expectancy since 1990. Diabetes led to a net loss of 0·09 years since 1990. There were variations between provinces in terms of age-standardised rates and the net change in life expectancy before and after the COVID-19 pandemic. The COVID-19 pandemic disrupted the rising trend of life expectancy in Iran, varying across provinces. Findings show that the health-care infrastructure and policies in Iran were not efficient in controlling the pandemic in 2020 and 2021, mainly due to inadequate vaccination coverage and timeliness, specifically for vulnerable subgroups. Sanctions may have aggravated the effect of COVID-19 on loss in life expectancy of Iranians. Despite the pandemic, the declining trend in age-standardised rates for top causes of mortality has continued to 2023, leading to a full recovery of life expectancy and underscoring the ultimate resilience of Iran's health system. Gates Foundation.

The efficacy and adverse reactions of Maren Runchang Pills among patients of different genders remain unclear. This study aims to analyze the efficacy and safety differences of Maren Runchang Pills in patients of different genders, providing a basis for the implementation of gender-precise treatment in clinical practice. Gender-stratified analysis was adopted to include constipation-predominant irritable bowel syndrome (IBS-C) patients who met the syndrome of intestinal heat and accumulation. The efficacy and safety of Maren Runchang Pills were evaluated after 4 weeks of treatment. The main evaluation indicators include the complete spontaneous bowel movement response rates, visual analogue scale scores for abdominal pain and distension, traditional Chinese medicine syndrome scores, irritable bowel syndrome-symptom severity scale/irritable bowel syndrome-quality of life scale scores, and safety indicators. A total of 126 patients were included, among whom 101 were female and 25 were male. After 4 weeks of treatment, the proportion of female patients with a complete spontaneous bowel movement response rate of ≥75% was significantly higher than that of male patients (71.29% vs 48%, P = .0270), and the improvement in abdominal distension visual analogue scale score was also significantly better in females (decrease of 2.78 points vs 1.84 points, P = .0199). However, the total score of traditional Chinese medicine syndromes in male patients was higher than that in female patients (7.08 points vs 5.09 points, P = .0341). There were no statistically significant differences in the scores of the irritable bowel syndrome-symptom severity scale, irritable bowel syndrome-quality of life scale and safety indicators between the 2 groups. Maren Runchang Pills can effectively alleviate the constipation symptoms of patients with IBS-C, and the therapeutic effect is even better in female patients. The research results support considering gender factors in the clinical treatment of IBS-C to achieve individualized and precise intervention.

Antibiotics are among the most concerning pharmaceutical contaminants released from municipal sewage treatment plants (STPs), occurring both in treated effluents and in dewatered biosolids. This study examines key analytical challenges during the determination of ten antibiotics in sewage wastes using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, results of their distribution in dewatered biosolids from different STPs are presented. Fluoroquinolones were identified as the most problematic compounds due to sorption on glassware, strong interaction with sample matrix, and signal suppression effects during LC-MS/MS analysis. Optimized extraction, based on sonication of freeze-dried samples with a buffered acetonitrile-water solution (pH 4.4, 1:1), yielded average recoveries between 74% and 108%, with moderate variability across sludge types. During simultaneous quantification of multiclass antibiotics, fluoroquinolones exhibited moderate to high signal attenuation depending on the matrix. For this group of compounds, signal suppression could be mitigated by fractionating extracts using mixed-mode (reversed phase and cation exchange) sorbents. Combined with isotopically labelled surrogate standards, solvent based calibration enabled accurate quantification of all targeted compounds, achieving limits of quantification below 5 ng g⁻¹. Azithromycin, clarithromycin, norfloxacin, ciprofloxacin and ofloxacin were ubiquitous in dewatered biosolids, with median concentrations ranging from 7 ng g-1 (clarithromycin) to 1761 ng g-1 (ofloxacin). A mass balance assessment of emissions through treated wastewater and biosolids highlighted azithromycin, ciprofloxacin, norfloxacin, and ofloxacin as the priority antibiotics for monitoring in final dewatered solid waste streams (biosolids) from STPs.

Photoelectrochemical (PEC) biosensors have attracted increasing interest for tumor biomarker detection due to their intrinsic advantages. However, conventional PEC sensing strategies are typically based on unidirectional "signal-on" or "signal-off" modes, which are vulnerable to matrix interferences in complex biological samples and may compromise analytical reliability. Photocurrent polarity switching (PPS) has recently emerged as an effective strategy to overcome these limitations, yet the development of efficient photoactive materials and rational signal-conversion mechanisms for PPS-based PEC biosensing remains a significant challenge. Metal-organic frameworks offer tunable electronic structures and high structural versatility, making them promising candidates for advanced photoelectrochemical sensing platforms. A novel photocurrent polarity-switching PEC aptasensor was developed for the ultrasensitive detection of the breast cancer biomarker CA15-3. Two-dimensional erbium-based MOF (Er-MOF) nanosheets were synthesized using H4TBAPy as the ligand and subsequently decorated with gold nanoparticles to form Er-MOF@AuNPs nanocomposites, which exhibit enhanced photoelectrochemical activity owing to localized surface plasmon resonance and good conductivity. A methylene blue-labeled aptamer was introduced as a redox-active signal probe, enabling target-triggered cathodic-to-anodic photocurrent inversion via a Z-scheme-like electron transfer pathway. Under optimized conditions, the anodic photocurrent showed a linear relationship with the logarithm of CA15-3 concentration in the range of 0.05 - 50 U/mL, with a detection limit of 0.0034 U/mL. The proposed aptasensor demonstrated excellent selectivity, reproducibility, photoelectrochemical stability, and satisfactory performance for assaying CA15-3 in human serum samples. This work establishes an Er-MOF-based PPS PEC sensing platform that integrates signal amplification and polarity-switchable readout into a single analytical system. The target-induced photocurrent inversion effectively suppresses background interference and enhances analytical accuracy, offering a robust alternative to conventional PEC sensing modes. The proposed strategy not only expands the application of Er-based MOFs in PEC biosensing but also provides a generalizable design concept for developing high-precision, anti-interference PEC sensors for clinical biomarker analysis.

Oligometastatic cancer is characterised by a low volume of metastases to a small number of anatomical sites. However, evaluating the impact of metastases-directed therapies (MDTs) on overall survival or quality of life is often challenging. Current clinical trials use a wide range of primary endpoints that might not be validated or suited to MDT. To address this issue, we did a systematic review of international trial registries, alongside a Delphi consensus process involving 30 experts and five patient representatives. The aim was to identify preferred primary endpoints for MDT trials in oligometastatic disease, regardless of tumour type. Overall survival and progression-free survival were the most frequently used endpoints across the 121 comparative trials reviewed. Over four Delphi consensus rounds, overall survival had the highest level of agreement, although its limitations as a sole endpoint were emphasised. In addition to the widely used progression-free survival endpoint, polymetastatic progression-free survival and start-or-switch of systemic therapy-free survival also reached consensus, particularly for trials integrating systemic therapies. Both polymetastatic progression-free survival and systemic therapy-free survival permit repeat MDT without classifying it as treatment failure. Patient representatives highlighted the importance of time-to-deterioration of quality of life. This consensus supports overall survival as a primary endpoint and, in addition to progression-free survival, recommends polymetastatic progression-free survival and systemic therapy-free survival, especially in combination with systemic therapies. Adopting these endpoints will make MDT trials more relevant, comparable, and patient-centred, thereby empowering future clinical and policy decisions.

To examine the association between prenatal exposure to benzodiazepines or Z-hypnotics and a spectrum of psychiatric disorders in children. Population based cohort study with sibling controlled analysis. National Health Information Database of South Korea, 2009-23. All liveborn children between 2010 and 2022 were followed until 2023. Pregnancies exposed to benzodiazepines or Z-hypnotics were compared with unexposed pregnancies and with pregnancies in women with previous use of these drugs (past users). Overall and 12 specific psychiatric disorders in offspring. Propensity score overlap weighting was applied to balance covariates, and hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards models. Sibling controlled analyses were conducted to account for shared familial factors. Among 3 809 949 liveborn children, 94 482 (2.5%) were exposed to benzodiazepines or Z-hypnotics during pregnancy, 3 715 467 were unexposed, and 147 307 were born to past users. During the follow-up period, a total of 10 060, 311 997, and 15 645 events occurred in the exposed, unexposed, and past user groups, respectively. Prenatal exposure was associated with a higher risk of psychiatric disorders compared with unexposed pregnancies and past users; however, this association was attenuated in the sibling controlled analysis (hazard ratio 0.99, 95% confidence interval 0.94 to 1.04). No increased risk was observed for individual psychiatric disorders. In subgroup analyses, modestly elevated hazard ratios were observed for exposure during the second half of pregnancy (sibling controlled hazard ratios: 1.27 (0.95 to 1.71) for benzodiazepine; 1.81 (0.57 to 5.74) for Z-hypnotic), during both the first and second half of pregnancy (sibling controlled hazard ratios: 1.35 (0.93 to 1.96) for benzodiazepine; 1.44 (0.93 to 2.21) for Z-hypnotic), and for 30 or more days of Z-hypnotic exposure (sibling controlled hazard ratio 1.31, 0.96 to 1.78), although the confidence intervals in sibling analyses were wide and included the null. In this large population based cohort, prenatal exposure to benzodiazepines or Z-hypnotics was not associated with an increased risk of psychiatric disorders in offspring after familial factors were accounted for. However, given the modest elevations in point estimates observed in certain subgroups-particularly with benzodiazepine and Z-hypnotic exposure during the latter half of pregnancy, as well as with exposure in both early and late pregnancy, and with longer durations of Z-hypnotic use-the potential for a slightly increased risk in these specific contexts could not be ruled out.

To explore barriers and enablers to the implementation of the Global Initiative for Asthma (GINA) recommendations in Jordan, building on prior quantitative survey findings. We aimed to examine healthcare professionals' experiences, perceptions and contextual challenges in translating guideline awareness into practice. Qualitative descriptive study using semi-structured interviews. Analysis was inductive thematic, guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ). Healthcare services in Jordan, including public hospitals, private hospitals, outpatient clinics and community pharmacies, spanning both urban and semi-urban areas. 28 healthcare professionals were purposively sampled to capture diverse roles, sectors and levels of experience. The sample included physicians (general practitioners and pulmonologists), pharmacists (community and hospital), nurses and Doctor of Pharmacy (PharmD) graduates. Eligibility required direct involvement in the management and counselling of adult patients with asthma within the preceding 12 months. Perceptions of and experiences with implementing GINA recommendations in clinical practice, focusing on provider-level, system-level and patient-level barriers and enablers. Eight interrelated themes were identified. A consistent 'know-do gap' emerged, whereby clinicians were aware of guidelines but reverted to habitual practice due to insufficient training, scepticism or lack of support systems. Limited diagnostic capacity, particularly the absence of spirometry in public settings, led to symptom-based management. Pharmacotherapy decisions were shaped by patient demand, entrenched short-acting β₂-agonist use and affordability concerns. Inhaler technique counselling and written action plans were infrequently provided, largely due to workload and unclear interprofessional roles. Patients' beliefs (eg, steroid fears, avoidance of inhalers during Ramadan, low health literacy) further impeded adherence. Despite these barriers, participants proposed pragmatic solutions, including concise locally adapted tools, structured Continuing Medical Education (CME), digital decision support, pharmacy-based inhaler technique clinics and public awareness campaigns. Asthma care in Jordan reflects a gap between GINA awareness and consistent application, driven by resource, organisational and cultural barriers. Improving outcomes will require system-level investment in diagnostic infrastructure, sustainable access to controller medications, interprofessional care models and culturally tailored patient education. These findings highlight the need for a coordinated national strategy to strengthen guideline implementation and provide a basis for developing policy and practice interventions across similar middle-income settings.

Organic acids are often used as pH modifiers in extended-release (ER) formulations to achieve pH-independent release of weakly basic drugs. These acids are intended to enhance drug release at intestinal pH by modifying the microenvironmental pH within the tablet matrix, thus reducing the pH-dependence of the drug release. However, the effectiveness of this approach depends on multiple factors, including the physicochemical properties of both the drug and the pH modifiers, formulation compositions, and drug loading. This study investigates the influence of pH modifiers on the pH-dependent release from ER hydrophilic matrix tablets containing four highly soluble acidic excipients using to facitinib (TOFA) as a model drug. The results demonstrated that the pH-dependence of TOFA release could be reduced to varying degrees depending on the specific acid used. Analysis of both drug and polymer release profiles indicated that the reduced pH-dependence was due not only to localized pH modulation, but also interactions between the acids and TOFA, as well as between acids and rate-controlling polymers. These findings provide valuable insights into the key factors that can influence the design of pH-independent ER hydrophilic matrix tablets for drugs with pH-dependent solubility.

Interactions between clinical pharmacists and industry partners continue to evolve as health care increases in complexity and technology assumes a more dominant role. To address the corresponding ethical challenges, the 2025 Industry Relations Committee of the American College of Clinical Pharmacy (ACCP) was charged with updating the 2008 ACCP position statement, Pharmacists and Industry: Guidelines for Ethical Interactions. This update expands its perspective, reflecting the broader and more influential roles pharmacists play across the health care ecosystem. All clinical pharmacist-industry interactions should be grounded in improving patient care. Through this lens, six recommendations are provided: (1) Pharmacists should not engage in industry partnerships or collaborations that might unduly influence objectivity, independence, or fairness in clinical and professional judgments; (2) Pharmacists should disclose and mitigate financial, consulting, or other relationships that constitute potential conflicts of interest and should not participate in activities where an existing conflict cannot be resolved; (3) Pharmacists who participate in industry-sponsored research should follow accepted ethical, regulatory, and scientific standards; (4) Pharmacists providing continuing education programs or developing drug information materials should maintain control of content; ensure their content is fair, balanced, and free from bias; and disclose and mitigate any conflicts; (5) Formal instruction on ethical interactions with industry professionals should begin early and continue through all stages of pharmacist education, training, and professional development; (6) Pharmacists should maintain the confidentiality and privacy of patients and other health care professionals when working with industry partners. Questions to guide personal industry interactions are provided. This paper does not detail every emerging area (e.g., artificial intelligence, social media), but recommendations are applicable wherever clinical pharmacists leverage their professional expertise. By maintaining a critical, discerning, and ethical approach to industry collaborations, clinical pharmacists can uphold professional obligations while contributing to the advancement of evidence-based practice, ultimately prioritizing patient welfare.

Regarding the limited clinical curative efficacy of CD47-targeted immunotherapy in treating oral squamous cell carcinoma (OSCC), the project aims to study the effect and mechanism of imiquimod-enhanced CD47 targeting in treating OSCC. The effect of imiquimod on enhancing the phagocytosis and clearance of OSCC cells of CD47 targeting was studied through phagocytosis experiments and cell clearance experiments. Then, the safety of the local application of imiquimod was confirmed, and the effect of imiquimod was verified in vivo by immunohistochemistry staining and tumor growth analysis. Finally, transcriptome sequencing, macrophage polarization, phagocytosis experiments, and cell clearance experiments were used to study the mechanism of imiquimod-enhanced CD47 targeting for treating OSCC. Imiquimod significantly enhances the phagocytosis and removal of OSCC cells when combined with CD47 targeting. In vivo studies have confirmed its capacity to potentiate CD47 targeting and revealed good biosafety of imiquimod. Mechanistically, imiquimod promotes M1 macrophage polarization by activating the Toll-like receptor (TLR)7-nuclear factor (NF)-κB pathway in macrophages. This activation enhanced the phagocytic capacity of macrophages to effectively remove OSCC cells. Imiquimod enhances CD47 targeting in phagocytosing and removing OSCC cells by activating macrophage TLR7-NF-κB activation and subsequent M1 polarization, providing a promising approach for treating OSCC.

The 5-year survival rate of early-stage hepatocellular carcinoma (HCC) patients remains only 60%, largely due to the inability to achieve ultra-early detection and safe, minimally invasive intervention of its premalignant precursor-high-grade dysplastic nodules (HGDN). Current clinical practice faces an unresolved dilemma: conventional imaging has limited sensitivity for HGDN, no standardized minimally invasive intervention exists, and no integrated platform enables synchronous detection, boundary localization and on-demand intervention, despite HGDN 80.8% 5-year HCC progression rate. To address these core challenges, we developed a multifunctional dual-hairpin DNA polydopamine nano-system (H/R@PDA-GC) targeting miRNA-224, a biomarker consistently upregulated during HGDN malignant transformation.This system enables specific detection of miRNA-224 with an ultra-low limit of detection (LOD) of 0.068 pM. Clinically, there is a 3-5-year natural history window from HGDN formation to clinically diagnosable early HCC; thus, this system provides a potential technical tool for the ultra-early warning of HCC at the precancerous stage. It simultaneously activates near-infrared fluorescence for targeted imaging of HGDN to precisely delineate lesion boundaries, and leverages its efficient photothermal conversion capability to achieve effective ablation of HGDN in validated murine models. Both cellular and animal studies confirmed its good in vitro and short-term in vivo biocompatibility, significant anti-inflammatory and antioxidant effects, and therapeutic efficacy, addressing the dual clinical needs of ultra-early detection and safe intervention of premalignant lesions. Consequently, H/R@PDA-GC provides an integrated theranostic strategy, which has potential clinical value for reducing the risk of HCC progression, and lays a foundation for ultra-early intervention of HCC precancerous lesions.Clinical trial number. Not applicable.

Aceclofenac (ACF) is a commonly used non-steroidal anti-inflammatory drugs (NSAID) for numerous inflammatory conditions; however, its therapeutic potential is limited due to suboptimal solubility. Pharmaceutical cocrystals have demonstrated favorable and sustainable results in improving the physicochemical and biopharmaceutical characteristics of poorly soluble drugs. To enhance the solubility, dissolution rate, and bioavailability of ACF, we aimed to prepare cocrystals of this biopharmaceutics classification system (BCS) class II drug with a coformer including nicotinamide (NCT), using hot melt extrusion (HME) and liquid-assisted grinding (LAG) methods. ACF-NCT cocrystals synthesized using these methods were characterized using various methods and were further assessed for in vitro anti-osteoporotic and in vivo anti-arthritic activities. The results indicate that both LAG and HME cocrystals demonstrated significant improvement in solubility and dissolution profile compared to pure ACF. However, among these two methods, HME offered more advantages, including better solubility and dissolution profile, than the LAG method. The cocrystals achieved a remarkable 6.15-fold increase in solubility and ⁓3-fold enhancement in dissolution over pure ACF. The relative bioavailability of ACF-NCT HME cocrystal was 249.98% of pure ACF, indicating an improvement in oral bioavailability. The in vivo anti-arthritic activity also demonstrated significant improvement when compared to pure ACF. ACF-nicotinamide cocrystals prepared by hot melt extrusion achieved remarkable gains in solubility, bioavailability, and therapeutic efficacy, providing a promising strategy to overcome ACF's clinical limitations.

Due to ideal stability, ease of preparation and high cost efficiency, nanozymes have been adopted as the substitutes of natural enzymes in homogeneous catalysis. However, the application of nanozymes was restricted caused by unsatisfactory emulsifying ability in heterogeneous catalysis. Albeit some asymmetric structures on Janus nanozymes are proposed for biphasic catalysis, the precise tuning of their amphiphilicity poses significant challenges especially through one-step self-assembly protocols. Herein, a facile controlled self-assemble protocol is developed to circumvent the utilization of the monophasic sphere as the beginner of Janus nanostructures. Pineapple-like Janus supports can be acquired by the simultaneous polymerization of resorcinol-formaldehyde resins and mesoporous SiO2 nanoparticles. Through the subtle alteration of dual precursors, the accurate tuning of asymmetric proportion allows for the tailorable amphiphilicity of Janus supports. By efficiently anchoring active Ce moieties onto Janus supports, asymmetric Ce@Janus nanozyme possesses superior kinematic locomotion and improved emulsion stabilization ability for dramatically boosting biphasic catalysis. Compared with monophasic nanozymes, Ce@Janus nanozyme with increased active sites and enhanced substrate affinity facilitates the biphasic chemiluminescent enhancement for the precise supervision of fentanyl with the detection limit of 0.47 pg·mL-1, by utilizing CDP-Star chemiluminescent reaction as a mode biphasic system. Moreover, the universality of the Janus support for biphasic nanozymes is demonstrated by the successful loading of a series of active metal sites including Pt, Cu, and Au for pressure sensing, colorimetric assay and photothermal analysis. The principle-of-proof work opens an avenue for the facile regulation of amphiphilic asymmetric nanozymes, which contributes to the intriguing biphasic catalysis efficiency for trace analysis.

IntroductionFinancial toxicity (FT) is more prevalent among rural-dwelling cancer survivors who also face greater cancer care-related travel burdens. We sought to examine how FT and travel burdens may pose dual burdens for cancer survivors, and assess their effects on care experiences and subsequent cost-coping strategies.MethodsRapid qualitative analysis of semi-structured interviews with rural-dwelling cancer survivors who screened positive for FT per the COmprehensive Score for financial Toxicity (COST) measure. Our analysis was structured around three inductive themes: rural-dwelling patients' experiences of cancer treatment while navigating FT, patient perceptions of travel burdens undertaken in the course of accessing cancer care, and perceived implications of both FT and travel burdens for care on HRQoL.ResultsThe (n = 12) participants in our study were mostly women, with a median age of 60.1. The median COST score was 9.5, indicating a high degree of FT, and the median round-trip travel distance was 25.6 miles. Participants reported cost-coping strategies to reduce travel-associated costs, such as "stacking" appointments to reduce travel costs and taking advantage of non-medical assistance offered by health systems' financial assistance programs (e.g., gas cards). Participants also reported shared burdens with caregivers who also shouldered costs.ConclusionsEstimates of travel distances to cancer care likely understate travel burdens, because they do not capture the frequency of appointments and their associated indirect and opportunity costs for cancer survivors experiencing FT. Financial assistance for cancer survivors should be responsive to the dual and cumulative financial and travel burdens of cancer care. Rural-dwelling cancer survivors are more likely to experience Financial Toxicity (FT) in tandem with greater cancer care-related travel burdens. This qualitative study sought to examine how FT and travel burdens may pose dual burdens for cancer survivors, and assess their effects on care experiences and subsequent cost-coping strategies. We conducted semi-structured interviews with (n = 12) participants sampled from the Lessening the Impact of Financial Toxicity (LIFT) study, an intervention that screened for FT and provided site-based financial navigation services and supports. Interview participants were mostly women, with a median age of 60.1. The median COmprehensive Score for financial Toxicity (COST) score was 9.5, indicating a high degree of FT, and the median round-trip travel distance was 25.6 miles. Participants reported cost-coping strategies to reduce travel-associated costs, such as “stacking” appointments to reduce travel costs and taking advantage of non-medical assistance offered health systems’ financial assistance programs (e.g., gas cards). Participants also reported shared burdens with caregivers who also shouldered costs. Concomitant caregivers- or cancer survivors who were also caregivers- were especially in need to supports to mitigate the dual burdens of cancer care-related FT and travel burdens.

Generalized pustular psoriasis (GPP) is a rare, systemic inflammatory disease characterized by a heterogeneous and often unpredictable clinical course involving chronic symptoms and recurrent flares. Due to the rarity of GPP, our understanding of factors associated with flare recurrence remains unclear. Using an existing data set of adult patients with GPP in Japan, we performed univariate and multivariate analyses to investigate potential factors related to GPP flare recurrence, including patient demographics,  treatment and severity of baseline flare. In total, 150 patients with a baseline flare were included in this analysis; 27.3% (n=41) experienced flare recurrence during the follow-up period (mean duration: 4.16 years). For the overall population, 56.0% of patients were male (n=84), the mean age at baseline was 55.5 years, and the mean body mass index was 24.3 kg/m2. Based on the Cox proportional hazards model, comorbid diabetes mellitus, a fever of ≥38.5°C at baseline flare, experience of flare(s) prior to baseline and certain respiratory infections were associated with a higher risk of flare recurrence, similar to previously published findings. These results could help identify patients at risk of GPP flares; however, clinically applicable prediction of GPP flares requires further research in a wider population.

This study presents an integrated approach utilising optical coherence tomography (OCT) to investigate the drug release mechanisms of hot-melt extruded (HME) amorphous solid dispersions (ASDs) of ritonavir and Soluplus®. Ritonavir-Soluplus® extrudates were prepared via HME using a twin-screw extruder and characterized during dissolution using a custom-designed 3D-printed flow cell, which enabled in-situ OCT imaging and continuous UV-vis monitoring of drug release. OCT provided high-resolution, time resolved visualization of structural transformations within the dissolving extrudates, while UV-vis spectroscopy quantified active pharmaceutical ingredient (API) release kinetics. Results revealed a multiphase dissolution mechanism involving sequential surface film formation, polymer swelling, delamination, and erosion. Increasing drug loading (10-30% w/w) produced marked effects on dissolution behaviour: formulations above 14% exhibited delayed release onset, extended swelling phases, and reduced overall release efficiency. OCT data showed that drug loadings above 14% led to slower erosion rates, greater swelling, and prolonged structural integrity, correlating with delayed UV-vis release profiles. Image processing using a machine learning segmentation model enabled quantitative extraction of sample cross-sectional area, confirming load-dependent swelling and erosion dynamics. Together, these findings establish a mechanistic link between structural evolution and release kinetics in HME ASDs and demonstrate the capability of OCT to provide real-time, non-destructive insight into solid dosage form dissolution. This methodology offers a powerful framework for optimizing ASD formulations and enhancing the predictive understanding of drug release mechanisms.

Although research on palliative care in hematological malignancies has increased, research examining quality of death (QOD) and quality of care (QOC) in this population remains limited. This study compared QOD and QOC between patients with hematological malignancies and those with solid tumors. The authors conducted a secondary analysis of a nationwide mortality follow-up survey of bereaved family members in Japan (2017-2018). The study included 3575 decedents with hematological malignancies and 50,592 with solid tumors. Propensity score matching was performed to adjust for demographic and clinical characteristics. QOD and QOC were assessed using the Good Death Inventory (GDI) and the Care Evaluation Scale 2.0 (CES). Bivariate analyses compared the matched groups. Overall, QOD and QOC were comparable between groups. However, among the GDI subdomains, patients with hematological malignancies had slightly lower scores for "good relationships with family" (mean difference, 0.2; 95% confidence interval [CI], 0.03-0.3) and "preparation for death" (mean difference, 0.2; 95% CI, 0.04-0.3). In addition, patients with hematological malignancies were less likely to die in palliative care units than those with solid tumors (mean difference, 3.9%; 95% CI, 0.4%-7.4%). Although overall quality measures were similar, specific QOD domains related to family relationships and preparation for death were slightly lower among patients with hematological malignancies. These findings may reflect limited opportunities for end-of-life discussions due to the unpredictable and rapidly progressive course of hematological malignancies. Enhancing communication about prognosis and goals of care and early integration of palliative care may improve end-of-life experiences.