OBJECTIVE To clarify the roles and functions of full-time pharmacists in the management of early-phase clinical trials of antineoplastic drugs， and to provide theoretical and practical support for their transformation from traditional drug managers to multi-dimensional roles in clinical research. METHODS Combined with relevant regulations such as the Good Clinical Practice （GCP） （2020 Edition）， and based on the clinical practice experience of the Phase Ⅰ Clinical Ward in our hospital， this study systematically sorted out full-time pharmacists’ roles and functions in early-phase clinical trials of antineoplastic drugs， and explored the core challenges and optimization pathways for role transformation and capacity-building of domestic full-time clinical trial pharmacists. RESULTS & CONCLUSIONS Full-time pharmacists assumed multiple roles in early-phase clinical trials of antineoplastic drugs， including providing pharmaceutical support for protocol design， implementing whole-process standardized management of clinical trial drugs， ensuring medication safety for clinical trial subjects/participants， conducting quality control throughout the clinical trial process， and serving as a bridge for interdisciplinary collaboration and communication. Currently， there are challenges in this field in China， such as unclear roles， an imperfect capacity building system， and insufficient regulatory support. This paper proposes that by establishing a standardized role framework， clarifying the core responsibilities and authorities of full-time pharmacists， and leveraging cutting-edge technologies to provide comprehensive support for their roles， so as to fully harness their pharmaceutical expertise and contribute to the standardization and efficiency of the antineoplastic new drug development process.

Objective To systematically analyze the spatiotemporal distribution characteristics and epidemiological trends of tracheal, bronchus, and lung cancer (TBL) disease burden attributed to air pollution globally and in China and the United States from 1990 to 2021, and to assess the patterns of disease burden changes from 2022 to 2031 based on predictive models, providing a scientific basis for formulating targeted TBL prevention and control strategies. Methods Based on the Global Burden of Disease (GBD) 2021 database, we analyzed the disease burden data of TBL attributed to air pollution globally and in China and the United States from 1990 to 2021. R Studio 4.3.2 software was used to analyze the corresponding trends and the Bayesian age-period-cohort (BAPC) prediction model was used to predict the status of the disease burden of TBL attributed to air pollution in the world and in China and the United States from 2022 to 2031. Results In 2021, China had the highest number of deaths and disability-adjusted life years attributed to air pollution (211 400 patients and 4.8947 million person-years), followed by the United States (6 000 patients and 124 300 person-years). The age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) of TBL due to air pollution in the world and in China and the United States showed a decreasing trend. From 1990 to 2021, the ASMR and ASDR of TBL in China due to air pollution were much higher than those in the United States and the global average. In terms of gender, from 1990 to 2021, the disease burden of male patients with TBL attributed to air pollution was much higher than that of female patients. The BAPC prediction model showed that from 2022 to 2031, the ASMR and ASDR of TBL attributed to air pollution showed an upward trend globally, while they showed a downward trend in China and the United States. Conclusion Over the past 30 years, the air pollution-related TBL disease burden in the world and in China and the United States has continued to decline, but China's disease burden is still significantly higher than the global average. The disease burden in men far exceeds that in women, with men and the population aged ≥50 years being high-risk groups. In the future, the global disease trend may reverse and rise, while China and the United States are expected to continuously decline. However, precise prevention and control for high-risk groups remains a key challenge.

ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

Objective To construct an index system for assessment of schistosomiasis transmission risk following natural disasters such as rainstorms, floods, earthquakes, mudslides, and landslides, so as to provide insights into rapid identification of schistosomiasis transmission risk post-disasters and formulation of targeted schistosomiasis control strategies. Methods An initial framework for the index system for assessment of schistosomiasis transmission risk following natural disasters was drafted through literature review, brainstorming, and focus group discussions. Two rounds of expert correspondence consultations were conducted using the Delphi method to refine and finalize the system, and the degrees of expert activeness, authority and endorse ment, and consensus were evaluated. In addition, the weights of each index were calculated using the analytic hierarchy process. Results A total of 18 experts participated in the consultation. The expert positive coefficients were 100.00% and 94.44% for two rounds of consultations, with authority coefficients of 0.92 and 0.94, respectively. The coefficients of coordination on the index importance, rationality and operability were 0.209, 0.185, 0.222 and 0.407, 0.214, 0.257 for two rounds of consultations, respectively, and all consistency tests were statistically significant (χ² = 246.771 to 505.278, all P values < 0.001). Following two rounds of expert consultations, an index system consisting of 6 first-level indicators, 15 second-level indicators, and 49 third-level indicators was ultimately constructed. In terms of first-level indicators, “disaster situation”, “previous epidemics”, “healthcare guarantee”, “response capacity” and “emergency recovery” had the highest weights, each at 18.18%. Regarding second-level indicators, “Schistosoma japonicum infections in animals”, “S. japonicum infections in snails” and “medical treatment” had the highest weights, each at 7.35%. In terms of third-level indicators, ten items had the highest weights, including “identification of schistosomiasis cases”, “detection of S. japonicum infections in wild feces”, “detection of S. japonicum infections in snails”, “reserves of schistosomiasis diagnostic/testing reagents and consumables”, “reserves of chemotherapy agents for human and animal schistosomiasis”, “reserves of cercariacides”, “periodical surveillance on schistosomiasis”, “identification of schistosomiasis transmission risk and timely response”, “normal provision of diagnosis and treatment services” and “post-disaster schistosomiasis surveillance”, each at 2.40%. Conclusion A scientific, systematic, and practical index system has been constructed for assessment of schistosomiasis transmission risk following natural disasters, which may provide insights into rapid post-disaster identification of schistosomiasis transmission risk, formulation of targeted schistosomiasis control strategies and optimization of resource allocation.

Objective To evaluate the efficacy and safety of CT-guided percutaneous radiofrequency ablation (RFA) as an alternative for video-assisted thoracoscopic surgery (VATS) in treating multiple pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of 113 patients with multiple pulmonary nodules admitted to Jiangsu Provincial Hospital of Traditional Chinese Medicine from October 2020 to October 2022. The patients were divided into the RFA group (n＝50) and the VATS group (n＝63) based on the treatment method. Perioperative indicators (operation time, intraoperative blood loss, postoperative length of hospital stay), oncological outcomes (recurrence-free survival [RFS], overall survival [OS]), and postoperative complication rates were compared between the two groups. Univariate and multivariate Cox regression analysis was performed to identify independent prognostic factors. Results The operation time in the RFA group was significantly shorter than that in the VATS group ([75.2±20.1] min vs [102.3±28.7]) min, P＜0.001). No statistically significant differences were observed in intraoperative blood loss and postoperative length of hospital stay. After follow-up of 24 (12, 30) months, no statistically significant differences were found in RFS (HR＝1.25, P＝0.445) or OS (HR＝1.42, P＝0.402) between the two groups. Mixed ground-glass nodules with high solid component and solid nodule were identified as independent risk factors for RFS (HR＝2.44, P＝0.023; HR＝2.97, P＝0.007) and OS (HR＝2.87, P＝0.022; HR＝3.43, P＝0.005) in patients with multiple pulmonary nodules. The total complication rate in the RFA group was lower than that in the VATS group (12.0% vs 34.9%, P＝0.009). Conclusions The efficacy of CT-guided RFA in treating multiple pulmonary nodules is comparable to that of VATS, with good safety, and it shows promise as an alternative to surgical treatment for multiple pulmonary nodules.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

ObjectiveTo explore the effect of cluster scalp acupuncture combined with Taijiquan training on depressive symptom, motor function, activities of daily living, serum markers, as well as brain functional connectivity (FC) and network topological properties in patients with post-stroke depression (PSD). MethodsA total of 40 PSD patients in the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine from September, 2022 to September, 2023 were enrolled and randomly divided into control group (n = 20) and experimental group (n = 20). The control group received cluster scalp acupuncture alone, while the experimental group underwent Taijiquan training in addition, for four weeks. They were assessed with Hamilton Depression Scale-17 (HAMD-17), Fugl-Meyer Assessment (FMA) and Barthel Index (BI) before and after treatment, while the serum levels of dopamine (DA), 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected with enzyme-linked immunosorbent assay. Resting-state functional magnetic resonance imaging (rs-fMRI) was applied to assess brain FC, as well as the global efficiency (Eg) and small-world property (σ) of brain networks. ResultsThe scores of HAMD-17, FMA and BI improved in both groups (t > 2.922, P < 0.01) after treatment, and improved more in the experimental group than in the control group (t > 2.517, P < 0.05). The serum levels of DA and 5-HT increased in both groups (t > 2.637, P < 0.05), and increased more in the experimental group (t > 2.192, P < 0.05). The serum levels of IL-6 and TNF-α decreased in the experimental group after treatment (t > 4.059, P < 0.001), and they were less than those in the control group (t > 2.154, P < 0.05). FC between left middle frontal gyrus and right anterior cingulate gyrus, as well as between left hippocampus and right precuneus were higher in the experimental group than in the control group after treatment (t > 3.867, P < 0.001), while Eg and σ increased in both groups (t > 2.828, P < 0.05), and they were higher in the experimental group (t > 2.675, P < 0.05). ConclusionCombination of Taijiquan training is more effective on depressive symptoms, motor function and activities of daily living in PSD patients, which may be related to up-regulation of serum DA and 5-HT, reduction of inflammatory factors, enhancement of prefrontal-limbic system functional connectivity and optimization of brain network topological properties.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Plant-derived extracellular vesicles (PDEVs) are nanoscale extracellular vesicles secreted by plant cells, characterized by a lipid bilayer structure. These vesicles carry a variety of bioactive molecules, including proteins, nucleic acids, and lipids, and play essential roles in intercellular communication and physiological regulation in plants. Compared to animal-derived extracellular vesicles, PDEVs offer several advantages, such as a broad range of sources, high biocompatibility, low immunogenicity, and low production costs. Furthermore, PDEVs have demonstrated remarkable potential as natural nanocarriers for drug delivery, due to their ability to efficiently traverse biological barriers, such as the blood-brain barrier, making them promising candidates for drug delivery systems. This review systematically elaborates on the complex composition of PDEVs, which consists of lipids, proteins, and nucleic acids, the typical structural characteristics of their lipid bilayers ranging from 30 to 150 nm, and their versatile loading capabilities as drug carriers, efficiently encapsulating various types of therapeutic agents such as hydrophilic small molecules, hydrophobic drugs, nucleic acids, and proteins. We systematically summarize the recent advancements in strategies for enhancing the loading efficiency of PDEVs, which include methods such as co-incubation, ultrasound-assisted loading, electroporation, freeze-thaw cycles, and microfluidic technology. These techniques are evaluated based on their underlying principles, suitable drug types, and their respective advantages. In addition to loading strategies, we focus on the engineered approaches to achieve targeted delivery using PDEVs, such as genetic engineering modifications, chemical ligand conjugation, membrane fusion technology, and polyethylene glycol (PEG) modification. We discuss the mechanisms of these strategies in enhancing targeting efficiency, prolonging in vivo circulation time, and improving therapeutic efficacy. Further, this review highlights the application of PDEVs in various disease models, including tumor, skin inflammation, metabolic disorders, and neurodegenerative diseases, showcasing their therapeutic potential as multifunctional delivery platforms. The ability of PDEVs to encapsulate diverse therapeutic agents and target specific tissues or cells opens up new avenues for the treatment of complex diseases, offering advantages over conventional drug delivery systems. However, despite the promising applications of PDEVs, several challenges remain in their development and clinical translation. These challenges include variability in source materials, standardization of preparation processes, quality control, scalability of production, and the need for clinical validation. To overcome these obstacles, the integration of advanced technologies such as artificial intelligence-assisted design and multi-omics analysis is proposed as a way to facilitate the precise development of PDEVs. These emerging technologies hold the potential to further enhance the precision and effectiveness of plant-based drug delivery systems, ultimately advancing the field of precision medicine. In conclusion, the use of PDEVs as a platform for drug delivery represents a promising area of research with the potential to revolutionize therapeutic strategies. Their ability to encapsulate and deliver a wide variety of bioactive molecules, along with their inherent advantages in biocompatibility and versatility, makes them a valuable tool in the development of more efficient and targeted therapeutic interventions. Continued research and innovation in this field will pave the way for the clinical implementation of PDEVs in the treatment of various diseases, offering new hope for more effective and sustainable therapeutic options.