Wenzhou Medical University

The clinical management of bacterial pneumonia (BP) induced by multidrug-resistant (MDR) pathogens poses substantial therapeutic challenges, necessitating urgent development of novel antibacterial agents and treatment paradigms, particularly those targeting deep-tissue...

Regulatory T cells (Tregs) play a crucial role in moderating immune responses offering promising therapeutic options for autoimmune diseases and allograft rejection. Genetically engineering Tregs with chimeric antigen receptors (CARs) enhances their targeting specificity and efficacy. With non‐viral transfection methods suffering from low efficiency and reduced cell viability, viral transduction is currently the only viable approach for GMP‐compliant CAR‐Treg production. However, viral transduction raises concerns over immunogenicity, insertional mutagenesis risk, and high costs, which limit clinical scalability. This study introduces a scalable nanoneedle electroporation (nN‐EP) platform for GMP‐compatible transfection of HLA‐A2‐specific CAR plasmids into primary human Tregs. The nN‐EP system achieves 43% transfection efficiency, outperforming viral transduction at multiplicity of infection 1 by twofold. Importantly, nN‐EP preserves Treg viability, phenotype and proliferative capacity. HLA‐A2‐specific CAR‐Tregs generated using nN‐EP show specific activation and superior suppressive function compared to polyclonal or virally transduced Tregs in the presence of HLA‐A2 expressing antigen presenting cells. These findings underscore the potential of nN‐EP as a GMP‐suitable method for CAR‐Treg production, enabling broader clinical application in immune therapies.

In this project, we studied the complete mitogenome of the liliaceae medicinal plant Polygonatum sibiricum. The genome is represented by a circular ring molecule with a length of 691,910 bp and a GC content of 46.33%. Mitochondrial genome composition is slightly biased towards A+T, with AT accounting for 53.67%, and AT skewness slightly positive (0.092%). The complete mitogenome has a total of sixty-three unique genes, including thirty-nine protein-coding genes, twenty-one transfer RNAs (tRNAs) and three ribosomal RNAs (rRNAs). We examined codon use, repeat sequence, RNA editing in the mitogenome of P. sibiricum, and elucidated species classification based on phylogenetic trees of mitogenome of twenty-three species. Our results provide comprehensive information on the mitogenome of P. sibiricum and show for the first time the evolutionary relationship between the mitogenome of P. sibiricum and Chlorophytum comosum in the Asparagales family.

Study design A cross-sectional study. Objective This study aims to investigate brain abnormal regional homogeneity alterations in patients with SSI. Summary of background data Recent research has demonstrated that patients with spinal sagittal imbalance (SSI) frequently experience gait disorders and postural instability. The brain is a crucial regulatory system that accomplishes controlled regulation of posture-gait synergy through complex mechanisms. However, investigations into the differences in brain function changes among patients with sagittal imbalance are lacking. Methods Twenty SSI patients and twenty healthy controls matched for age, gender, and education level were enrolled. All participants underwent global spine X-ray and resting-state functional magnetic resonance imaging (rs-fMRI). Kendall’s coefficient of concordance was calculated for whole-brain analysis in each group. Two-sample t-tests were performed to identify differences in brain regions between the two groups. Additionally, we explored the relationship between clinical evaluations (sagittal vertical axis, Oswestry Disability Index (ODI), and regional homogeneity (ReHo) values) in brain regions. Results Compared to healthy controls, the SSI group exhibited increased ReHo values in the following brain regions (all P < 0.01): Cerebellum Crus 1 Left (Cerebellum_Crus1_L ,(Anatomical Automatic Labeling:AAL)), Superior Temporal Gyrus Right(Temporal_Sup_R (AAL)), Superior Frontal Gyrus Medial Right(Frontal_Sup_Medial_R (AAL)), and Supplementary Motor Area Left(Supp_Motor_Area_L (AAL)). Furthermore, our results revealed that the Cerebellum_Crus1_L (AAL) ReHo value was negatively correlated with ODI scores for sitting, lifting, walking, standing, and overall function, as well as the Physical Functioning (PF) score. Conversely, it showed a positive correlation with the Reported Health Transition (HT) score. The Temporal_Sup_R (AAL) ReHo value demonstrated negative correlations with ODI walk and General Health (GH) scores. The Frontal_Sup_Medial_R (AAL) ReHo value in the SSI group was negatively correlated with ODI walk but positively correlated with Mental Health (MH). Finally, the Supp_Motor_Area_L (AAL) ReHo value exhibited negative correlations with ODI scores for lifting, walking, sitting, standing, and overall function, as well as the PF score and sagittal vertical axis (SVA) measurement. However, it displayed positive correlations with Social Functioning (SF) and HT scores. Conclusion These findings indicate significant alterations in ReHo within the Cerebellum_Crus1_L (AAL), Temporal_Sup_R (AAL), Frontal_Sup_Medial_R (AAL), and Supp_Motor_Area_L (AAL) regions in patients with SSI. The present study suggests that ReHo abnormalities could serve as a potential biomarker for further elucidating the neuropathological mechanisms, clinical diagnosis, and targeted treatment of patients with sagittal imbalance.

Background Since long COVID has hindered people from normal life, it is essential to understand its full spectrum of manifestation. However, it was heterogeneous in the existing studies and few large-scale studies have been conducted on Asian populations. Here, we conducted a multi-centre questionnaire-based study among Chinese people to explore the long COVID based on the definition of WHO. Methods During March 20, 2023 and June 18, 2023, individuals with a history of confirmed or self-reported SARS-CoV-2 infection were recruited from three hospitals to fill out the questionnaire for long COVID. Each symptom was assigned with 0 to 3 points based on their severity. And the long COVID score was a sum of these points of each symptom. The reporting rate, time trend and risk factors of long COVID stratified by different systems were explored. Results 3,693 individuals were recruited for the study. The reporting rate of at least one persistent long COVID symptoms and symptoms impacting daily life was 30.2% (1,117) and 10.7% (394). Systemic symptoms (20.7%, 765) were most easily reported. The most common symptoms were fatigue (16.3%, 602), cough (6.3%, 234) and expectoration (5.5%, 203). The reporting rate of long COVID and long COVID score decreased over time during a 180-day follow-up period (P < 0.05). For long COVID, older age (OR: 1.63, 1.38–1.93), female (OR: 1.19, 1.03–1.38) and SARS-CoV-2 reinfection (OR: 3.56, 2.63–4.80) were risk factors; while number of COVID-19 vaccine doses (OR: 0.87, 0.81–0.94) was a protective factor. The use of traditional Chinese medicine (OR: 0.51, 0.37–0.71) was a protective factor for symptoms impacting daily life. Conclusions Early interventions should be taken to minimize the impact of long COVID, especially for the elderly, females and those with SARS-CoV-2 reinfection. COVID-19 booster vaccination might play a potential role in minimizing the impact of long COVID.

Background Chemotherapy side effects can easily contribute to malnutrition and disrupt the normal diet of breast cancer patients. Offering early multidisciplinary team interventions during chemotherapy can establish a solid groundwork for dietary management and enhance the quality of life throughout the survival period. This study aims to assess the impact of early multidisciplinary team interventions on dietary management behavior, self-care self-efficacy, quality of life, and body mass index in breast cancer patients undergoing chemotherapy. Methods A prospective, two-arm, single-blind, single-center randomized controlled trial was conducted between November 2023 and July 2024 from a tertiary-level general hospital in Shaanxi, China. A total of 88 participants who were either preparing for or undergoing early or middle stage chemotherapy were enrolled for this intervention. The intervention group received diet-related early multidisciplinary team interventions, in addition to the usual dietary education. The control group only received the usual dietary education. The intervention program included 8 themes, which were covered each week. The data on dietary management behavior, self-care self-efficacy, quality of life, and body mass index were measured at baseline (T0), immediately after the intervention (T1), 1 month after (T2), and 3 months after (T3) the intervention. Results Seventy-nine participants, divided into an intervention group of 40 and a control group of 39, completed all the measures. There were statistically significant intergroup effects between the two groups and time effects on dietary management behavior, self-care self-efficacy, and quality of life. Additionally, there was an interaction effect (P < 0.05). However, there was no statistically significant intergroup effect on body mass index before and after the intervention (P > 0.05). Conclusion The early multidisciplinary team interventions are an effective method for improving dietary management behavior and confidence among breast cancer patients undergoing chemotherapy. Nurses should be attentive to the dietary issues faced by female patients during chemotherapy and should work to train and organize a multidisciplinary team to provide this intervention. This may lay a theoretical and capable foundation for managing a healthy lifestyle for future survival period. Trial registration This intervention was registered with the Chinese Clinical Trials Registry (ChiCTR2300076503, October 10, 2023).

This study aims to conduct a comprehensive bibliometric analysis of ET research, focusing on contributions from authors, institutions, and countries or regions, while mapping collaboration networks. Furthermore, it identifies development trends to provide insights for future research. A bibliometric analysis of ET-related publications (2001–2024) was conducted using data from the Web of Science Core Collection, focusing on publication trends, co-authorship networks, co-citation relationships, and citation bursts. A total of 4,297 studies published in 778 journals were included in the analysis. ET research has grown rapidly, with major contributions from researchers in the United States and Europe, particularly through extensive collaborations. Leading figures such as Ayalew Tefferi and Alessandro M. Vannucchi have driven advances in ET classification, molecular mechanisms, and targeted therapies. The discovery of driver mutations, such as JAK2, has revolutionized the diagnostic and therapeutic approaches to ET. Research focus has shifted from clinical morphological diagnosis to molecular diagnostics, with the field now entering the era of targeted therapies. However, the heterogeneity of ET, the limitations of targeted therapies, particularly the lack of management experience and data for high-risk and special populations, as well as the incomplete understanding of the role of inflammation in the disease mechanism, continue to hinder both clinical and scientific progress in ET research. Bibliometric analysis demonstrates significant advances in ET research, particularly in molecular pathology and targeted therapies. Future research should address ET heterogeneity, optimize management of high-risk and special populations, overcome the limitations of targeted therapies, and further elucidate the role of inflammation to achieve individualized precision therapy.

High-grade lung neuroendocrine carcinomas (Lu-NECs) are clinically refractory malignancies with poor prognosis and limited therapeutic advances. The biological and molecular features underlying the histological heterogeneity of Lu-NECs are not fully understood. In this study, we present a multi-omics integration of whole-exome sequencing and deep proteomic profiling in 93 Chinese Lu-NECs to establish the first comprehensive proteogenomic atlas of this disease spectrum. Our analyses revealed a high degree of mutational concordance among the subtypes at the genomic level; however, distinct proteomic profiles enabled a clear differentiation of histological subtypes, unveiling subtype-specific molecular and biological features related to tumor metabolism, immunity, and proliferation. Furthermore, RB1 mutations confer divergent prognostic effects through subtype-specific cis- and trans-proteomic regulation. In addition, we identified potential protein biomarkers for histological subtype classification and risk stratification, which were validated by immunohistochemistry in an independent cohort. This study provides a valuable proteogenomic resource and insight into Lu-NEC heterogeneity.

Function‐encoding peptides have emerged as promising biomaterials capable of replicating the robust biological functions of the extracellular matrix (ECM). Nevertheless, the full potential of their sequence designability remains to be explored to develop highly bioactive peptide‐based biomaterials with minimal immunogenicity. In this study, chiral peptides are self‐assembled into supramolecular hydrogels (FFFKTTKS/fffkttks) incorporating an active sequence derived from collagen hydrolysis, a key ECM factor. While FFFKTTKS (L‐type) and fffkttks (D‐type) peptide‐based hydrogels exhibit comparable viscoelasticity, porosity, and supramolecular architecture, they differ in their nanofiber composition, particularly in helical orientation. In a model of spinal cord injury, the FFFKTTKS hydrogel demonstrates superior neuronal regeneration and motor function recovery compared to its fffkttks counterpart. Further investigations reveal that both FFFKTTKS and fffkttks hydrogels equally promote the expression of ECM‐related genes, subsequently regulating nerve cell adhesion, neuronal differentiation, and synaptic regeneration. Notably, the FFFKTTKS hydrogel elicits a mild immune response and exhibits moderate anti‐inflammatory properties. In contrast, the fffkttks hydrogel triggers a robust immune response, activating the TNF pathway in microglia in vivo. These findings underscore that nanoscale chiral superstructures of specific peptide sequences can effectively modulate biocapability and neuroregeneration, providing critical insights for the rational design of peptide‐based synthetic ECM.

Background Acinetobacter baumannii is a major pathogen in hospitals, causing a notable rise in bloodstream infections among inpatients. Its growing resistance to multiple drugs limits treatment options. This study aims to examine the antibacterial effects of gallium nitrate [Ga(NO3)3] against A. baumannii and elucidate the underlying molecular mechanism. Methods 40 strains of A. baumannii with different antimicrobials susceptibility patterns were isolated from bloodstream infections. The in vitro antibacterial activity of Ga(NO3)3 was analyzed by micro-dilution method and time-kill assay. The influence of ferric chloride/hemin on the antibacterial efficacy of Ga(NO3)3 was investigated. Transcriptome sequencing was performed to elucidate the antibacterial mechanism of Ga(NO3)3. A mouse infection model was conducted to assess its in vivo performance. Results Ga(NO3)3 exhibited a potent antibacterial effect in RPMI 1640 medium containing 10% human serum, with MICs ranging from 0.06 μg/mL to 0.125 μg/mL. The antibacterial activity of Ga(NO3)3 was found to be dose- and time- dependent. However, the antibacterial effect of Ga(NO3)3 was partially compromised in the presence of exogenous ferric chloride/hemin. Transcriptomics analysis revealed that Ga(NO3)3 exerted its antibacterial effect by up-regulating the expression of genes associated with siderophore biosynthesis and transport, while simultaneously disrupting multiple iron-dependent metabolic processes. Ga(NO3)3 treatment significantly reduced bacterial load in vivo using a neutropenic mouse thigh infection model. Conclusion This study sheds light on the antibacterial mechanisms of Ga(NO3)3 against A. baumannii, suggesting its potential as a promising antibacterial drug for treating bloodstream infections caused by multidrug-resistant A. baumannii.

Background Pharmaceutical graduate education often faces a gap between basic theoretical knowledge and the practical realities of drug research, resulting in a limited understanding of new drug development among graduate students. Therefore, it is necessary to implement pharmaceutical education based on the principles and practices of translational medicine to help students gain a deeper understanding of the drug development process and to cultivate professionals capable of translating basic research findings into clinical applications. Methods Pharmaceutical graduate students at Campus A (172 students) were taught using traditional methods, while students at Campus B (203 students) were taught using a reformed approach. The reformed class focused on building an interdisciplinary teaching team, selecting faculty with experience in new drug development and a background in translational medicine, to strengthen the connection between clinical and basic research. Additionally, the course content was designed to reflect the latest advancements in the field, breaking away from traditional textbooks. Various disease models were used to explain the application of translational medicine in pharmacy. The course employed a variety of teaching methods, including theoretical lectures, interactive seminars, case discussions, and expert-led workshops, to enhance students’ understanding of cutting-edge topics and stimulate innovative thinking while addressing real-world clinical issues. Finally, the assessment focused on process-oriented evaluation, using group presentations, literature reviews, and other diverse methods to comprehensively assess both academic and practical abilities. Results The comparison of theoretical knowledge exam scores (converted to a percentage scale) between the traditional and reformed class revealed a statistically significant difference (P < 0.05), indicating that students in the reformed class had a better grasp of the theoretical knowledge. In the innovative drug development proposal project, the traditional class consisted of 17 teams, while the reformed class had 20 teams. The independent t-test showed a significant difference in the average scores between the two groups (P < 0.01), suggesting that the reformed class developed stronger drug development strategies based on clinical problems. Furthermore, the results of the student satisfaction survey indicated that students in the reformed class responded positively to the new teaching methods, with only a single-digit number of students reporting dissatisfaction, indicating broad acceptance. Conclusions The reform of the pharmaceutical graduate course “Biopharmaceuticals and Translational Medicine,” based on the principles of translational medicine, not only enhances students’ understanding of the drug development process but also better prepares them for careers in pharmaceutical research and clinical applications.