Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity* ; Animals ; Mice ; Cardiotoxicity/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Proteomics ; Metabolomics ; Injections ; Humans ; Multiomics

Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

OBJECTIVES: To study the differences in clinical characteristics of term and preterm neonates with necrotizing enterocolitis (NEC) undergoing surgical treatment. METHODS: A retrospective analysis was conducted on the clinical data of 142 NEC neonates who underwent surgery at the Children's Hospital of Chongqing Medical University from June 2017 to August 2023. The neonates were categorized into a preterm group (gestational age <37 weeks; 95 cases) and a term group (gestational age 37-42 weeks; 47 cases) to compare clinical characteristics. RESULTS: The preterm group had a higher postnatal age at both diagnosis and surgery compared to the term group (P<0.05). The preterm group also had a higher incidence of preoperative bloody stools, lower preoperative platelet counts, and higher rates of preoperative respiratory distress, apnea, reduced/absent bowel sounds, and mechanical ventilation compared to the term group (P<0.05). Postoperatively, the preterm group had higher rates of purulent meningitis, sepsis, and coagulation dysfunction, lower postoperative platelet counts, and lower intraoperative minimum body temperature than the term group (P<0.05). CONCLUSIONS There are significant differences in the clinical characteristics of preterm and term neonates with NEC undergoing surgery, suggesting the need for tailored perioperative management strategies based on these characteristics.
Humans ; Enterocolitis, Necrotizing/surgery* ; Infant, Newborn ; Retrospective Studies ; Male ; Female ; Infant, Premature ; Gestational Age

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective: To preliminarily develop a multidimensional blood donor role scale based on role theory and systematically compare the psychosocial characteristic differences between award-winning donors and first-time donors in Guangzhou, and to provide an empirical reference for formulating differentiated donor retention strategies. Methods: A cross-sectional survey design was adopted. A random sample of award-winning donors and concurrently sampled first-time donors yielding 1 361 valid responses collected (721 from the award group, 640 from the first-time group). Exploratory factor analysis was used to assess the scale structure. Data were post-stratified and weighted according to the gender and age distributions of the general donor population. Independent samples t-tests, multivariate analysis of covariance (MANCOVA), and generalized linear models were employed to compare dimensional scores between the two groups. A paired t-test was conducted to analyze the annual donation frequency of award-winning donors before and after receiving the award. Results: Exploratory factor analysis yielded a 5-factor structure, including Role Identity and Expectations, Role Adaptation and Maintenance, Role Environment and Experience, Role Relationships and Conflict, and Role Incentives and Rewards, with a cumulative variance contribution rate of 56.43%. The scale demonstrated good internal consistency reliability (Cronbach's α=0.906). Known-group validity test showed that award-winning donors scored significantly higher than first-time donors on Role Identity and Expectations (t=4.366, P<0.001, d=0.240), Role Adaptation and Maintenance (t=5.436, P<0.001, d=0.500), and Role Relationships and Conflict (t=4.844, P<0.001, d=0.220). These differences remained significant after controlling for selected demographic variables (MANCOVA, Wilks' λ=0.943, P<0.001). Generalized linear models suggested that donation frequency was an independent predictor for these dimensions. Additionally, the annual donation frequency of award-winning donors was slightly higher after receiving the award than before (t=2.007, P=0.045). Conclusion: The preliminary blood donor role scale demonstrates acceptable reliability and validity and can effectively distinguish groups with different donation behavior characteristics. The study reveals that award-winning donors exhibit more positive psychological characteristics across multiple role identity dimensions and maintain their donation behavior after receiving an award. External incentives and internal role identity may jointly contribute to behavioral persistence. The findings provide a preliminary reference for further exploring the formation pathways of donor role identity and developing differentiated donor retention strategies.